MEMCAL    SCHOOL 


Gift  of 


Panama-Pacific  Intern1 
Exposition  Company. 


HALLIBUBTON'S 
HANDBOOK   OF   PHYSIOLOGY 


HANDBOOK  OF 
PHYSIOLOGY 


BY     W.    D.    HALLIBURTON,    M.D. 

LL.D.,  F.R.C.P.,  F.R.S. 

PROFESSOR  OF   PHYSIOLOGY,   KING'S  COLLEGE,    LONDON 


ELEVENTH    EDITION 

(BEING  THE  TWENTY-FOURTH  EDITION  OF  KIRKES'  PHYSIOLOGY) 


WITH    NEARLY    SIX    HUNDRED   ILLUSTRATIONS    IN    THE   TEXT,    MANY 
OF    WHICH    ARE   COLOURED,    AND   THREE   COLOURED    PLATES 


COMPLIMENTS 
OF 


s  fa  COL 


PHILADELPHIA 

P.    BLAKISTON^S    SON    &    CO. 

1012  WALNUT  STREET 

1914 


Printed  in  Great  Britain. 


PEEFACE  TO  THE  ELEVENTH  EDITION 

ONCE  more  this  book  has  been  thoroughly  revised.  The  sections 
dealing  with  salivary  secretion,  the  formation  of  urine,  and  much 
of  the  chapter  on  respiration  have  been  almost  entirely  rewritten. 
New  matter  on  the  process  of  conduction  in  the  heart,  on  the  appli- 
cations of  physical  chemistry  to  physiology,  on  so-called  vitamines, 
and  several  other  subjects  has  been  introduced.  The  concluding 
chapter  on  reproduction  and  development  is  a  new  one,  and 
replaces  the  two  last  chapters  in  previous  editions. 

I  am  again  indebted  to  several  kind  friends  for  assistance  in 
carrying  out  my  task.  I  would  especially  thank  Mr  Barcroft,  F.E.S., 
for  his  valuable  help  in  the  chapters  that  deal  with  saliva,  respira- 
tion, and  the  kidney ;  Dr  C.  S.  Myers,  who  has  kindly  revised  the 
parts  which  deal  with  the  special  senses ;  Dr  Hertz  of  Guy's  Hospital, 
for  useful  hints  in  bringing  the  chapter  on  the  movements  of  the 
stomach  and  intestines  up  to  date ;  and  Dr  F.  H.  A.  Marshall,  for 
similar  kind  offices  in  relation  to  the  subject  of  reproduction. 

I  think,  in  conclusion,  I  may  congratulate  my  readers  that, 
although  the  present  edition  contains  so  much  that  is  new  both 
in  text  and  illustrations,  I  have  been  successful  in  introducing  this 
additional  information  without  increasing  the  bulk  of  the  volume. 
As  a  matter  of  fact,  this  edition  is  one  page  shorter  than  the 
last. 

W.  D.  HALLIBUETOK 

KING'S  COLLEGE,  LONDON, 
1913. 


8(5 


CONTENTS 


CHAPTER   I 

PAGE 
INTRODUCTORY        ..••••••• 


CHAPTER    II 
THE  ANIMAL  CELL  .  ...  7 

CHAPTER   III 

EPITHELIUM  .....••••         20 

CHAPTER    IV 
THE  CONNECTIVE  TISSUES  .  .  .  •  •  •  •  .28 


CHAPTER   V 


THE  CONNECTIVE  TISSUES—  continued 


37 


Cartilage 37 

Bone 

Teeth ... 

The  Blood  60 


CHAPTER   VI 

MUSCULAR  TISSUE  .  .  .  •  •  •  •  • 

vii 


Vlll  CONTENTS 

CHAPTER   VII 

PAGE 

NERVE        •«......  73 

CHAPTER   VIII 

IRRITABILITY  AND  CONTRACTILITY             .....  81 

CHAPTER    IX 

CHANGE  IN  FORM  IN  A  MUSCLE  WHEN  IT  CONTRACTS     .  .87 

Instruments  used        .....  87 

Simple  Muscle  Cur  re.            ...  96 

The  Muscle- Wave      .....  100 

Effect  of  two  Successive  Stimuli        .            .            .            .  .            .101 

Effect  of  more  than  two  Stimuli        .            .            .            .  .101 

Tetanus           .......  .101 

Voluntary  Tetanus     ......  104 

CHAPTER   X 

EXTENSIBILITY,  ELASTICITY,  AND  WORK  OF  MUSCLE      .             .  .             .108 

CHAPTER   XI 

THE  ELECTRICAL  PHENOMENA  OF  MUSCLE            .            .            .  .116 

CHAPTER  XII 

THERMAL  AND  CHEMICAL  CHANGES  IN  MUSCLE  .             .             .  .             ,129 

Fatigue  .........       132 

Rigor  Mortis  ......  136 

Chemical  Composition  of  Muscle       .            .            .  .            .136 

CHAPTER   XIII 

COMPARISON  OF  VOLUNTARY  AND  INVOLUNTARY  MUSCLE  140 


CONTENTS  IX 

CHAPTER  XIV 

PAGE 

PHYSIOLOGY  OF  NERVE      .             .  .             .            .             .            .  .143 

Classification  of  Nerves          .  .            .            .            .            .  .143 

Investigation  of  Nerve  Functions  .            .            .            .            .  .146 

Degeneration  of  Nerve           .  .            .            .            .            .  .146 

Regeneration  of  Nerve  .......       148 

Roots  of  the  Spinal  Nerves  .  .            .                        .            .  .155 

Changes  in  Nerve  during  Activity  .            .            .            .            .  .158 

Velocity  of  a  Nerve  Impulse.  .            .            .            .            .  .159 

Direction  of  a  Nerve  Impulse  .....  160 

Crossing  of  Nerves     .            .  .            .            .            .            .  .161 

The  Nature  of  the  Nerve  Impulse  .            .            .            .            .  .       163 

Receptive  Substances             .  .            .            .            .            .  ,164 

Chemistry  of  Nervous  Tissues  ......       165 

CHAPTER   XV 

ELECTROTONUS         .  .  .  .  .  .  .  .  .169 

CHAPTER   XVI 

NERVE  CENTRES     .........       180 

Structure  of  Nerve-Cells 182 

The  Law  of  Axipetal  Conduction      .  .  .  .  .  .191 

The  Significance  of  Nissl's  Granules  .  .  .  .  .192 

Classification  of  Nerve-Cells  according  to  their  Function    .  .  .194 

CHAPTER   XVII 

THE  AUTONOMIC  NERVOUS  SYSTEM  .  .  .  .  .  .196 

CHAPTER   XVIII 
TROPHIC  NERVES    .........       206 

CHAPTER   XIX 

THE  CIRCULATORY  SYSTEM  .......       208 

The  Heart 208 

Course  of  the  Circulation        .......       214 

Structure  of  Arteries  ......  .216 

Structure  of  Veins      .  .  .  .  .  .  .  .218 

Structure  of  Capillaries  and  Sinusoids  .....       222 

Structure  of  Lymphatic  Vessels        .  .  .  .  .  .223 

CHAPTER   XX 

THE  CIRCULATION  or  THE  BLOOD  ......       227 


CONTENTS 


CHAPTER   XXI 

PAGE 

PHYSIOLOGY  or  THE  HEART  .  .  .  .  .  .  .       232 

The  Cardiac  Cycle      ........       232 

Action  of  the  Valves  of  the  Heart .234 

Sounds  of  the  Heart  ........       235 

Coronary  Arteries       ........       237 

Cardiographs  .  .  .  .  .  .  .  .  .       238 

Intracardiac  Pressure  .  .  .  .  .  .  .240 

The  Electro-Cardiogram        .  .  .  .  .  .  .243 

Frequency  of  the  Heart's  Action      .  .  .  .  .  .247 

Work  of  the  Heart     ........       247 

Innervation  of  the  Heart        .......       249 

Rhythm,  Conduction,  etc. ,  in  Heart  Muscle  ....       254 

The  Isolated  Heart    .  260 


CHAPTER  XXII 

THE  CIRCULATION  IN  THE  BLOOD-VESSELS  .  .  .  .  .263 

Use  of  the  Elasticity  of  the  Vessels  .  .  .  .  .  .265 

Blood-pressure  .  .  .  .  .  .  .  .       266 

Velocity  of  the  Blood-flow     .......       281 

The  Time  of  a  Complete  Circulation  .  .  .  .  .289 

The  Pulse      .  .  .  .  .  .  .  .  .  .290 

The  Capillary  Flow  .  .  .  .  .  .  .297 

The  Venous  Flow       ......  .299 

The  Vaso-motor  Nervous  System      ......       300 

Plethysmography       ........       308 

Pathological  Conditions          .  .  .  .  .  .  .311 

Local  Peculiarities  of  the  Circulation  312 


CHAPTER  XXIII 

LYMPH  AND  LYMPHATIC  GLANDS              .  .  .  .             .             .315 

Composition  of  Lymph          .            .  .  .  .            .            .315 

Lymphatic  Glands     ...  ....       316 

Lymph  Flow  ....  ...       31 8 

Relation  of  Lymph  and  Blood           .  .  .  .            .            .319 

Formation  of  Lymph .            .            .  .  .  .            .            .319 


CHAPTER   XXIV 
PHYSICAL  CHEMISTRY  AND  ITS  BEARING  ON  PHYSIOLOGICAL  PROBLEIMS.  .       322 


CONTENTS  XI 

CHAPTER   XXV 

PAGE 

THE  DUCTLESS  GLANTDS     ........       331 

Spleen  .........       332 

Haemolymph  Glands  .  .  .  .  .  .  .  .       336 

Thymus  .  .  .  .  .  .  .  .  .336 

Thyroid  .........       337 

Parathyroids    .........       339 

Supra-renal  Capsules  .  .  .  .  .  .  .  .       340 

Pituitary  Body  ........       343 

Pineal  Gland  .........       345 

Coccygeal  and  Carotid  Glands          .  .  .  .  .  .345 

CHAPTER   XXVI 

RESPIRATION  .  .  .  .  .  .  .  .  .346 

Respiratory  Apparatus  .  .  .  .  .  .  .346 

Respiratory  Mechanism         .......       354 

Graphic  Record  of  Respirations         .  .  .  .  .356 

The  Gases  of  the  Blood          .  .  .  .  .  .  .361 

Solution  of  Gases  in  Water    .  .....       361 

Dalton-Henry  Law     ....  ...       362 

Tension  of  Gases  in  Fluids     .......       362 

Measurement  of  Quantity  of  Gas  in  Fluids .  .  .  .  .363 

Relation  between  Quantity  and  Tension      .....       365 

The  Mechanism  of  Gaseous  Exchange  in  the  Lung  .  .  .372 

1.  Oxygen  ........       372 

2.  Carbonic  Acid  .......       375 

Cause  and  Regulation  of  Respiration  .....       375 

1.  The  Respiratory  Centre         ......       375 

2.  The  Nervous  Factor  in  Respiration  .....       376 

3.  The  Chemical  Factor  in  Respiration  .  .  .  .380 

Special  Respiratory  Acts        .  .  .  .  .  .  .381 

Artificial  Respiration .  .  .  .  .  .  .  .383 

Ventilation      .........       384 

CHAPTER   XXVII 

THE  RELATION  OF  RESPIRATION  TO  OTHER  PROCESSES  IN  THE  BODY     .  .       385 

Effect  of  Respiration  on  the  Circulation        .....       385 

Asphyxia         .........       389 

Relation  of  Respiration  to  Nutrition  .....      392 

Oxygen  Want  ........       398 

Mountain  Sickness     ........       400 

Respiration  at  High  Pressures          .  .  .  .  .  .402 

Carbon  Monoxide  Poisoning .  ......       403 

Cheyne-Stokes  Respiration    .  .  .  .  .  .404 

Diabetic  Coma  405 


CONTENTS 


CHAPTER    XXVIII 

PAGE 

THE  CHEMICAL  COMPOSITION  or  THE  BODY         .             .             .             .  406 

Carbohydrates             ...  406 

^ts ;      ;  414 

Proteins            .                         .......  416 

LiP°ids             .........  434 

Enzymes          ......  438 


CHAPTER   XXIX 

THE  BLOOD              .......  444 

Coagulation  of  the  Blood       .....  .       446 

The  Plasma  and  Serum          .....  452 

The  Blood-Corpuscles             .            .             .            ,             ,  .            .454 

Development  of  the  Blood-Corpuscles           .            .            .  .            .459 

Chemistry  of  the  Blood-Corpuscles    .            .            .            v  .            .461 

Haemoglobin   ...,..,  .461 

Immunity        .......  472 


CHAPTER   XXX 

FOOD           ..........  479 

Dietaries          ......  479 

Milk .'  481 

The  Mammary  Glands           .......  485 

Eggs     ..........  486 

Meat    ..........  487 

Flour   .  .  .  .  .  .  .  .  .  .488 

Bread  ..........  489 

Cooking  of  Food         ......                        .  489 

Accessories  to  Food    .......  490 

Unknown  but  Essential  Constituents  of  Food         .  491 


CHAPTER   XXXI 
THE  ALIMENTARY  CANAL;  SECRETING  GLANDS  .....       492 

CHAPTER   XXXII 

SALIVA        ..........       498 

The  Salivary  Glands  .  .  .  .  .  .  .  .498 

The  Secretion  of  Saliva          .  .  .  .  .  .  .       500 

Secretory  Nerves  of  Salivary  Glands  .  .  .  .  .502 

The  Saliva        ......  504 


CONTENTS  Xlll 

CHAPTER   XXXIII 

PAGE 

THE  GASTRIC  JUICE  .  .......       507 

I  nnervation  of  the  Gastric  Glands    .  .  .  .  .  .511 

Action  of  Gastric  Juice          .  .  .  .  .  .  .513 

CHAPTER   XXXIV 

DIGESTION  IN  THE  INTESTINES       .  .  .  .  .  .  .517 

The  Pancreas 517 

Composition  and  Action  of  Pancreatic  Juice  .  .  .  .518 

The  so-called  Peripheral  Reflex  Secretion  of  the  Pancreas  .  .       520 

The  Succus  Entericus  .  .  .  .  .  .  .       522 

Bacterial  Action          .  .  .  .  .  .  .       525 

CHAPTER   XXXV 

THE  LIVER  .........       527 

Bile 531 

Glycogenic  Function  of  the  Liver     .  .  .  .  .  .536 

Diabetes  .........       538 

The  Liver  and  Fat  Metabolism          .  .  .  .  .  .541 

CHAPTER    XXXVI 
THE  ABSORPTION  OF  FOOD  .......       543 

CHAPTER   XXXVII 

THE  MECHANICAL  PROCESSES  OF  DIGESTION         .  .  .  .  .       550 

Mastication      .  .  .  .  .  .  .  .  .550 

Deglutition      .  .  .  .  .  .  .  .  .551 

Movements  of  the  Stomach    .  .  ...  .  .  .553 

Vomiting          .........       556 

Movements  of  the  Intestines  .  .  .  .  .  .  .557 

CHAPTER   XXXVIII 

THE  URINARY  APPARATUS  .......       565 

The  Nerves  of  the  Kidney     .  .  .  .  .  .  .571 

The  Kidney  Oncometer          .  .  .  .  .  .  .571 

The  Functions  of  the  Kidney  .  .  ;  .  .  .572 

Extirpation  of  the  Kidneys    .......       579 

Passage  of  Urine  into  the  Bladder    ......       580 

Micturition      .  580 


XIV  CONTENTS 

CHAPTER   XXXIX 

PAGE 

THE  URINE  .  .  .  .  .  .  .  582 

Urea    ..........       583 

Ammonia         .........       588 

Creatine  and  Creatinine         .  .  .  .  .  .  .589 

Uric  Acid        .  .  .  .  .  .  .  .591 

HippuricAcid  ........       594 

Inorganic  Constituents  of  Urine        ......       595 

Urinary  Deposits     .   .  .  .  .  .  .  .  .       598 

Pathological  Urine     ........       600 

CHAPTER   XL 

THE  SKIN  AND  ITS  APPENDAGES  .  .  .  .  .  .  .604 

CHAPTER   XLI 

GENERAL  METABOLISM       .  .  .  .  .  .  .  .612 

Balance  in  Health       ........       613 

Metabolism  of  Carbohydrates  .  .  .  .  .  .614 

Metabolism  of  Fat     .  .  .  .  .  .  .  .616 

Metabolism  of  Protein  .......       621 

Growth  and  Maintenance      .......       626 

Inanition  or  Starvation          .......       628 

CHAPTER   XLII 
THE  CONSERVATION  OF  ENERGY   .......       630 

CHAPTER   XLIII 
TEMPERATURE         .........       636 

CHAPTER   XLIV 

THE  CENTRAL  NERVOUS  SYSTEM  ....  .  642 

CHAPTER   XLV 
STRUCTURE  OF  THE  SPINAL  CORD  ......       648 

CHAPTER   XLVI 

STRUCTURE  OF  THE  BULB,  PONS,  AND  MID-BRAIN  .  .  .  .661 

The  Cranial  Nerves    .  673 


CONTENTS  XV 

CHAPTER   XLVII 

PAGE 

STRUCTURE  OF  THE  CEREBELLUM  ...          .          •   680 

CHAPTER   XLVIII 

STRUCTURE  OF  THE  CEREBRUM  .......       686 

The  Convolutions        .  .             .             .             .             .             •             .691 

Histology  of  the  Cortex  .            .            .            .                         .            .695 

The  White  Matter      .  .....       698 

CHAPTER   XLIX 

FUNCTIONS  OF  THE  SPINAL  CORD  .  .  .  .  .  .  •       704 

The  Cord  as  an  Organ  of  Conduction  .....       704 

Reflex  Action  of  the  Cord .       709 

Reflex  Action  in  Man  .  .  .711 

The  Principle  of  the  Common  Path  ...  716 

Reaction  Time  .....  .720 

Spinal  Visceral  Reflexes        .  .  ....       721 

CHAPTER   L 

FUNCTIONS  OF  THE  CEREBRUM       .....  .       722 

Removal  of  the  Cerebrum      .......       722 

Localisation  of  Cerebral  Functions    .  .  .  .  .  .725 

Function  and  Myelination      .  .  .  .  .  .  .739 

Association  Fibres  and  Centres          ......       740 

Electrical  Variation    .  .  .  .  .  .  .743 

Sleep  and  Narcosis      ........       744 

CHAPTER    LI 

FUNCTIONS  OF  THE  CEREBELLUM  ......  .       749 

The  Semicircular  Canals         .......       752 

CHAPTER   LII 

THE  PHYSIOLOGY  OF  CONSCIOUS  STATES   .  .  .  .  .  .757 

CHAPTER   LII1 

CUTANEOUS  SENSATIONS      .             .            .             .             .             .  .             .766 

Tactile  End-Organs    .....  .       766 

Localisation  of  Tactile  Sensations     .            .            .            .  .            .770 

Varieties  of  Cutaneous  Sensations    ....  .772 


XVI  CONTENTS 

CHAPTER   LIV 

PAGK 

MOTORIAL   AND    VlSCERAL   SENSATIONS          .                  .                  .                  .  775 

CHAPTER   LV 

TASTE  AND  SMELL  ......  779 

Taste   ..........  779 

Smell   .....            .            .            .            .    -        .  783 

CHAPTER   LVI 

HEARING      .......             ...  788 

Anatomy  of  the  Ear   ........  758 

Physiology  of  Hearing            .....  794 

CHAPTER   LVII 

VOICE  AND  SPEECH             •••...  799 

Anatomy  of  the  Larynx         .....  799 

Movements  of  the  Vocal  Cords          ....  804 

The  Voice       .......            .'            !  806 

Speech  .  .  .  .  .  .  .  m  .807 

Defects  of  Speech       .            .            .            .            .            .  808 


CHAPTER    LVIII 

THE  EYE  AND  VISION        ......  810 

The  Eyeball    .........  811 

The  Eye  as  an  Optical  Instrument    ....  820 

Accommodation          .......  824 

Defects  in  the  Optical  Apparatus      ......  828 

The  Skiascope             ......  831 

Functions  of  the  Iris  ......  832 

Functions  of  the  Retina          ......  834 

The  Ophthalmoscope              .......  836 

The  Perimeter             ........  839 

Visual  Sensations  and  Colour  Vision             ...                         .  841 

Changes  in  the  Retina  during  Activity         .  .  .  .  .847 

Movements  of  the  Eyeballs   ......  849 

Nervous  Paths  in  the  Optic  Nerves  ....  .853 

Visual  Judgments      .....  854 


CONTENTS  XV11 

CHAPTER    LIX 

PAQK 

REPRODUCTION,  DEVELOPMENT,  GROWTH  AND  DEATH     ....       858 

The  New-born  Child  and  its  Development  .....       862 

The  Male  Reproductive  Organs         .  .  .  .  .  .863 

The  Female  Reproductive  Organs    .  .  .       867 

The  Physiology  of  the  Reproductive  Organs  ....       872 

Spermatogenesis ........       872 

Oogenesis  .  .  .  .  .  .  .873 

Menstruation        ........       873 

Maturation  of  the  Ovum  ......       875 

Internal  Secretions  of  Ovary  and  Testis  .  .  .  .878 

Fertilisation    .........       881 

Segmentation  .  .  .  .  .  ...  .883 

The  Decidua  and  the  Foetal  Membranes      ...  .887 

The  Foetal  Circulation  .......       891 

Parturition       .........       893 

Death  ..........       895 

INDEX  897 


COLOURED  PLATES 

VARIETIES  OF  COLOURLESS  CORPUSCLES  ....  to  face  page  456 

PLATE  or  ABSORPTION  SPECTRA  .  .  .  .  .  ,,         ,,  466 

SIMULTANEOUS  AND  SUCCESSIVE  CONTRAST          .  .  .  ,,         ,,  845 


FAHRENHEIT 
and 

MEASUREMENTS. 

CENTIGRADE 

SCALES. 

LENGTH. 

A  grain  equals  about  1*16  gram., 
a  Troy  oz.  about  31  grams., 

F. 

500" 

C. 

260° 

10  "edmetresl      -  ^lf1^ 

and  1  cwt.  about  50  Kilogrms. 

401 

205 

1000  millimetres  J  ^or  l  yard  and  3*  ^ 

CAPACITY. 

392 

200 

383 

374 

195 
190 

1  decimetre    "|            g.937  mches 

1,000,000  cubic  centimetres  /     metre. 

356 
347 
338 
329 

180 
175 
170 
165 

1  cubic  decimetre         ^ 
or                        V  =  1  litre. 
1000  cubic  centimetres      J 

320 

160 

1  centimetre  \      =  '3937  or  about 

OR, 

311 

155 

10  millimetres  J        (nearly  \  inch). 

ONE  LITRE  =  1  pt.  15  oz.  1  dr.  40. 

302 

284 

150 
140 

1  millimetre           =  nearly  ,V  mch- 

(For  simplicity,  Litre  is  used  to  signify 

275 

135 

1  cubic  decimetre,  a  little  less  than  1 

266 

130 

English  quart.) 

248 

120 

ONE  METRE  =  39-37079  inches. 

Decilitre  (100  c.c.)            =  3£  oz. 

239 
230 
212 
203 
194 

115 
110 

100 
95 
90 

(It  is  the  ten-millionth  part  of  a  quarter 
of  the  meridian  of  the  earth.) 
1  Decimetre     =     4  in. 
1  Centimetre    =     T^  in. 
1  Millimetre     —      L  in 

Centilitre  (10  c.c.)            =  2*  dr. 
Millilitre  (1  c.c.)              =  17  m. 
Decalitre                            =  2|  gals. 
Hectolitre                          =  22  gals. 
Kilolitre  (cubic  metre)  -  27£  bushels. 

176 

80 

Decametre        ~~     32-80  feet 

A  cubic  inch  =  16-38  c.c.  ;  a  cubic  foot 

167 
140 
122 

75 
60 
50 

Hectometre      =     109-36  yds. 
Kilometre         =    0-62  mile. 

=  28-315  cubic  dec.,   and  a  gallon  = 
4-54  litres. 

113 

45 
40  '54 

One  foot     =     3-047  Decimetres. 

CONVERSION    SCALE. 

104 

40 

One  yard     =     0~91  of  a  Metre. 

To  convert  GRAMMES  to  OUNCES  avoir- 

100 

37-8 

One  mile     =     1-60  Kilometre. 

dupois,  multiply  by  20  and  divide  by  567. 
To  convert  KILOGRAMMES  to  POUNDS, 

98-5 

369 

WEIGHT 

multiply  by  1000  and  divide  by  454. 
To  convert  LITRES  to  GALLONS,  mul- 

86 

77 

30 

25 

(One  gramme  is  the  weight  of  a  cubic 
centimetre  of  water  at  4°  C.  at  Paris.) 

tiply  by  22  and  divide  by  100. 
To  convert  LITRES  to  PINTS,  multiply 
by  88  and  divide  by  50. 

50 
41 
32 
23 

10 
5 
0 
-   5 

1  gramme           "\ 
10  decigrammes    I      =  15-432349  grs. 
100  centigrammes  j       (or  nearly  150. 
1000  milligrammes  J 

To  convert  MILLIMETRES  to  INCHES, 
multiply  by  10  and  divide  by  254. 
To  convert  METRES  to  YARDS,  multi- 
ply by  70  and  divide  by  64. 

+  5 
-    4 
-13 

-15 
-20 
-25 

1  decigramme    ^      =      th 
10  centigrammes  V     tn™i»  grain 
100  milligrammes  J 

SURFACE   MEASUREMENT. 

1  square  metre  =  about  1550  sq.  inches 
(or  10,000  sq.  centimetres,  or  10-75  sq.ft.) 

-22 

-30 

-40 
76 

-40 
-60 

1  centigramme  )      =  rather  more 

1  sq.  foot   =     „      930    „             „ 

ENERGY   MEASURE 

1     deg.  F.  =  -54°  C. 

1  milligramme          =  rather  more 

1  kilogrammetre  =  about  7*24  ft.  pounds. 

1-8     „         =    1°C. 

than  jj-jlfl  grain. 

1  foot  pound        =     „      -1381  kgm. 

Freezing  point  0°  C. 

=    32°  F. 

OR, 

1  foot  ton             =     „      310  kgms. 

Boiling  point  100°  C. 
=     212°  F. 

1  Decagramme  —  2  dr.  34  gr. 
1  Hectogrm.      =  3£  oz.  (Avoir.) 
1  Kilogrm          —  2  Ib.  3  oz.  2  dr.  (Avoir. 

HEAT    EQUIVALENT. 

1  kilocalorie  =  425-5  kilogrammetres. 

To   convert    de- 
grees  F.    into   de- 
grees C.,  subtract 

ENGLISH    MEASURES. 

32,    and    multiply 

ty  §. 

Apothecaries  Weight. 

Avoirdupois  Weight. 

7000  grains     -     1  Ib 

To    convert    de- 

Or 

16  oz.              =     1  Ib. 

grees    C.    into    de- 

28 Ibs.             =     1  quarter. 

grees  F.,  multiply 
by  f  ,  and  add  82°. 

437-5  grains     ^     1  oz. 

4  quarters    =     1  cwt. 
20  cwt.            =     1  ton. 

Measure  of  1  decimetre,  or  10  centimetres,  or  100  millimetres. 


10 


HANDBOOK  OF  PHYSIOLOGY 


CHAPTEE    I 

INTRODUCTORY 

via  the  science  that  treats  of  living  things,  and  it  is  divided 
into  two  main  branches,  which  are  called  respectively  Morphology 
and  Physiology.  Morphology  is  the  part  of  the  science  that  deals 
with  the  form  or  structure  of  living  things,  and  with  the  problems 
of  their  origin  and  distribution.  Physiology,  on  the  other  hand, 
treats  of  their  functions,  that  is,  the  manner  in  which  their  individual 
parts  carry  out  the  processes  of  life.  To  take  an  instance:  the  eye 
and  the  liver  are  two  familiar  examples  of  what  are  called  organs ; 
the  morphologist  or  anatomist  studies  the  structure  of  these  organs, 
their  shape,  their  size,  the  tissues  of  which  they  are  composed,  their 
position  in  the  body,  and  the  variations  in  their  structure  met  with 
in  different  parts  of  the  animal  kingdom.  The  physiologist  studies 
their  uses,  and  seeks  to  explain  how  the  eye  fulfils  the  function  of 
vision,  and  how  the  liver  forms  bile,  and  ministers  to  the  needs  of 
the  body  in  other  ways. 

Each  of  these  two  great  branches  of  biological  science  can  be 
further  subdivided  according  as  to  whether  it  deals  with  the  animal 
or  the  vegetable  kingdom;  thus  we  get  vegetable  physiology  and 
animal  physiology.  Human  physiology  is  a  large  and  important 
branch  of  animal  physiology,  and  to  the  student  of  medicine  is 
obviously  the  portion  of  the  science  that  should  interest  him  most. 
In  order  to  understand  morbid  or  pathological  processes  it  is  neces- 
sary that  the  normal  or  physiological  functions  should  be  learnt  first. 
Physiology  is  not  a  study  which  can  be  put  aside  and  forgotten  when 
a  certain  examination  has  been  passed ;  it  has  a  most  direct  and 
intimate  bearing  in  its  application  to  the  scientific  and  successful 
investigation  of  disease.  It  will  be  my  endeavour  throughout  the 
subsequent  pages  of  this  book  to  point  out  from  time  to  time  the 
practical  relationships  between  physiology  and  pathology. 


2  INTRODUCTORY  [CH.  1. 

Human  physiology  will  be  our  chief  theme,  but  it  is  not  a  portion 
of  the  great  science  that  can  be  studied  independently  of  its  other 
portions.  Thus,  many  of  the  experiments  upon  which  our  knowledge 
of  human  physiology  rests  have  been  performed  principally  on  certain 
of  the  lower  animals.  In  order  to  obtain  a  wide  view  of  vital  pro- 
cesses it  will  be  occasionally  necessary  to  go  still  further  afield,  and 
call  the  science  of  vegetable  physiology  to  our  assistance. 

The  study  of  physiology  must  go  hand  in  hand  with  the  study  of 
its  sister  science  anatomy,  but  the  sciences  of  chemistry  and  physics 
must  also  be  considered.  Indeed,  physiology  has  been  sometimes 
defined  as  the  application  of  the  laws  of  chemistry  and  physics  to 
life.  That  is  to  say,  the  same  laws  that  regulate  the  behaviour  of 
the  mineral  or  inorganic  world  are  also  to  be  found  operating  in  the 
region  of  organic  beings.  If  we  wish  for  an  example  of  this  we  may 
again  go  to  the  eye ;  the  branch  of  physics  called  optics  teaches  us, 
among  other  things,  the  manner  in  which  images  of  objects  are  pro- 
duced by  lenses;  these  same  laws  regulate  the  formation  of  the 
images  of  external  objects  upon  the  sensitive  layer  of  the  back  of  the 
eye  by  the  series  of  lenses  in  the  front  of  that  organ.  An  example 
of  the  application  of  chemical  laws  to  living  processes  is  seen  in 
digestion ;  the  food  contains  certain  chemical  substances  which  are 
acted  on  in  a  chemical  way  by  the  various  digestive  juices  in  order  to 
render  them  of  service  to  the  organism. 

The  question  arises,  however,  is  there  anything  else  ?  Are  there 
any  other  laws  than  those  of  physics  and  chemistry  to  be  reckoned 
with  ?  Is  there,  for  instance,  such  a  thing  as  "  vital  force  "  ?  It 
may  be  frankly  admitted  that  physiologists  at  present  are  not  able  to 
explain  all  vital  phenomena  by  the  laws  of  the  physical  world ;  but 
as  knowledge  increases  it  is  more  and  more  abundantly  shown  that 
the  supposition  of  any  special  or  vital  force  is  unnecessary ;  and  it 
should  be  distinctly  recognised  that  when,  in  future  pages,  it  is 
necessary  to  allude  to  vital  action,  it  is  not  because  we  believe  in  any 
specific  vital  energy,  but  merely  because  the  phrase  is  a  convenient 
one  for  expressing  something  that  we  do  not  fully  understand,  some- 
thing that  cannot  at  present  be  brought  into  line  with  the  physical 
and  chemical  forces  that  operate  in  the  inorganic  world. 

But  just  as  there  is  no  hard-and-fast  line  between  physiology 
and  its  allies  pathology,  anatomy,  physics,  and  chemistry,  so  also 
there  is  no  absolute  separation  between  its  three  great  divisions; 
physical,  chemical,  and  so-called  vital  processes  have  to  be  considered 
together. 

Physiology  is  a  comparatively  young  science.  Though  Harvey 
more  than  three  hundred  years  ago  laid  the  foundation  of  our  science 
by  his  discovery  of  the  circulation  of  the  blood,  it  is  only  during  the 
last  sixty  or  seventy  years  that  active  growth  has  occurred.  The 


CH.  I.]  INTRODUCTORY  3 

reasons  for  this  recent  progress  come  under  two  headings:  those 
relating  to  observation  and  those  relating  to  experiment. 

The  method  of  observation  consists  in  accurately  noting  things 
as  they  occur  in  nature ;  in  other  words,  the  knowledge  of  anatomy 
must  be  accurate  before  correct  deductions  as  to  function  are  possible. 
The  instrument  by  which  such  correct  observations  can  be  made  is, 
par  excellence,  from  the  physiologist's  standpoint,  the  microscope,  and 
it  is  the  extended  use  of  the  microscope,  and  the  knowledge  of  minute 
anatomy  resulting  from  that  use,  which  has  formed  one  of  the  greatest 
stimuli  to  the  successful  progress  of  physiology  during  recent  times. 

But  important  as  observation  is,  it  is  not  the  most  important 
method;  the  method  of  experiment  is  still  more  essential.  This 
consists,  not  in  being  content  with  mere  reasonings  from  structures  or 
occurrences  seen  in  nature,  but  in  producing  artificially  changed 
relationships  between  the  structures,  and  thus  causing  new  combina- 
tions that  if  one  had  waited  for  Nature  herself  to  produce  might  have 
been  waited  for  indefinitely.  Anatomy  is  important,  but  mere 
anatomy  has  often  led  people  astray  when  they  have  tried  to  reason 
how  an  organ  works  from  its  structure  only.  Experiment  is  much 
more  important ;  that  is,  one  tests  one's  theories  by  seeing  whether 
the  occurrences  actually  take  place  as  one  supposes ;  and  thus  the 
deductions  are  confirmed  or  corrected.  It  is  the  universal  use  of  this 
method  that  has  made  physiology  what  it  is.  Instead  of  sitting  down 
and  trying  to  reason  out  how  the  living  machine  works,  physiologists 
have  actually  tried  the  experiment,  and  so  learnt  much  more  than 
could  possibly  have  been  gained  by  mere  cogitation.  Many  experi- 
ments involve  the  use  of  living  animals,  but  the  discovery  of  anaes- 
thetics, which  renders  such  experiments  painless,  has  got  rid  of  any 
objection  to  experiments  on  the  score  of  pain. 

The  adult  body  consists  of  a  great  number  of  different  parts ;  and 
each  part  has  its  own  special  work  to  do.  Such  parts  of  the  body  are 
called  organs.  Each  organ  does  not  only  its  own  special  work,  but 
acts  in  harmony  with  other  organs.  This  relationship  between  the 
organs  enables  us  to  group  them  together  into  what  are  termed 
systems.  Thus,  we  have  the  circulatory  system,  that  is,  the  group  of 
organs  (heart,  arteries,  veins,  etc.)  concerned  in  the  circulation  of  the 
blood;  the  respiratory  system,  that  is,  the  group  of  organs  (air 
passages,  lungs,  etc.)  concerned  in  the  act  of  breathing ;  the  digestive 
system,  which  deals  with  the  digestion  of  food ;  the  excretory  system, 
with  the  getting  rid  of  waste  products ;  the  muscular  system,  with 
movement ;  and  the  skeletal  system,  with  the  support  of  the  softer  parts 
of  the  body.  Over  and  above  all  these  is  the  nervous  system  (brain, 
spinal  cord,  nerves),  the  great  master  system  of  the  body  which  pre- 
sides over,  controls,  and  regulates  the  functions  of  the  other  systems. 

If  we  proceed  to  make  an  anatomical  analysis,  and  take  any 


INTRODUCTORY 


[CH.  I. 


organ,  we  see  that  it  consists  of  various  textures,  or,  as  they  are 
called,  elementary  tissues.  Just  as  one's  garments  are  made  up  of 
textures  (cloth,  lining,  buttons,  etc.),  so  each  organ  is  composed  of 
corresponding  tissues.  The  elementary  tissues  come  under  the 
following  four  headings: — 

1.  Epithelial  tissues.  3.  Muscular  tissues. 

2.  Connective  tissues.  4.  Nervous  tissues. 

Each  of  these  is  again  divisible  into  subgroups. 

If  we  continue  our  anatomical  analysis  still  further,  we  find 
that  the  individual  tissues  are  built  up  of 
structures  which  require  the  microscope  for 
their  accurate  study.  Just  as  the  textures 
of  a  garment  are  made  up  of  threads  of 
various  kinds,  so  also  in  many  of  the  animal 
tissues  we  find  threads  or  fibres,  as  they  are 
called.  But  more  important  than  the  threads 
are  little  masses  of  living  material.  Just  as 
the  wall  of  a  house  is  made  up  of  bricks 
united  by  cement,  so  the  body  walls  are  built 
of  extremely  minute  living  bricks,  united 
together  by  different  amounts  of  cementing 
material.  Each  one  of  these  living  units  is 
called  a  cell. 

Some  of  the  tissues  already  enumerated 
consist  of  cells  with  only  very  little  cement 
material  binding  them  together;  this,  for 
instance,  is  seen  in  the  epithelial  tissues; 

but  in  other  tissues,  particularly  the  connective  tissues,  which  are 
not  so  eminently  living  as  the  rest,  the  amount  of  cement  or  inter- 
cellular material  is  much  greater,  and  in  this  it  is  that  the  fibres 
are  developed  that  confer  the  necessary  strength  upon  these  binding 
tissues. 

If,  instead  of  going  to  the  adult  animal,  we  look  at  the  animal 
in  its  earliest  stage  of  development,  the  ovum,  we  find  that  it  con- 
sists of  a  single  little  mass  of  living  material,  a  single  cell.  As 
development  progresses  it  becomes  an  adherent  mass  of  cells.  In  the 
later  stages  of  development  various  tissues  become  differentiated 
from  each  other  by  the  cells  becoming  grouped  in  different  ways,  by 
alterations  in  the  shape  of  the  cells,  by  deposition  of  intercellular 
matter  between  the  cells,  and  by  chemical  changes  in  the  living 
matter  of  the  cells  themselves.  Thus  in  some  situations  the  cells  are 
grouped  into  the  various  epithelial  linings ;  in  others  the  cells  become 
elongated  and  form  muscular  fibres;  and  in  others,  as  in  the  con- 
nective tissues,  there  is  a  preponderating  amount  of  intercellular 


Space  con- 
taining 
liquid. 


Protoplasm. 


' — '  Nucleus. 


—     Cell-wall. 


Fm.  1.— Vegetable  cells. 


CH.  I.]  INTRODUCTORY  5 

material  which  may  become  permeated  with  fibres,  or  be  the  seat  of 
the  deposition  of  calcareous  salts,  as  in  bone.  Instances  of  chemical 
changes  in  the  cells  themselves  are  seen  on  the  surface  of  the  body, 
where  the  superficial  layers  of  the  epidermis  become  horny ;  in  the 
mucous  glands,  where  they  become  filled  with  mucin,  and  in  adipose 
tissue,  where  they  become  charged  with  fat. 

The  term  cell  was  first  used  by  botanists ;  in  the  popular  sense 
of  the  word  a  cell  is  a  space  surrounded  by  a  wall,  as  the  cell  of  a 
prison,  or  the  cell  of  a  honeycomb.  In  the  vegetable  cell  there  is  a 
wall  made  of  the  starch-like  material  called  cellulose ;  within  this  is 
the  living  matter,  and  a  number  of  large  spaces  or  vacuoles  filled 
with  a  watery  fluid.  The  use  of  the  term  cell  by  botanists  was 
therefore  completely  justified. 

But  the  animal  cell  is  different ;  as  a  rule,  it  has  no  obvious  cell- 
wall,  and  vacuoles  are  not  conspicuous.  It  is  just  a  little  naked 
lump  of  living  material.  This  living  material  is  jelly-like  in  con- 
sistency, possessing  the  power  of  movement,  and  the  name  proto- 
plasm has  been  bestowed  on  it. 

Somewhere  in  the  protoplasm  of  all  cells,  generally  near  the  middle 
in  animal  cells,  is  a  roundish  structure  of  more  solid  consistency  than 
the  rest  of  the  protoplasm,  called  the  nucleus. 

An  animal  cell  may  therefore  be  defined  as  a  mass  of  protoplasm 
containing  a  nucleus. 

The  simplest  animals,  such  as  amoebae,  consist  of  one  cell  only; 
the  simplest  plants,  such  as  bacteria,  torulaa,  etc.,  consist  of  one 
cell  only. 


FIG.  2. — Amoebae;  unicellular  animals.  Fm.   3. — Cells  of   tb.e  yeast 

plant  in  process  of  bud- 
ding ;  unicellular  plants. 

These  organisms  are  called  unicellular.  In  the  progress  of  their 
life  history  the  cell  divides  into  two ;  and  the  two  new  cells  separate 
and  become  independent  organisms,  to  repeat  the  process  later  on. 

The  higher  animals  and  plants  are  always  unicellular  to  start 
with,  but  on  dividing  and  subdividing  the  resulting  cells  stick 
together  and  subsequently  become  differentiated  and  altered  in  the 
manner  already  indicated.  In  spite  of  these  changes,  the  variety 
of  which  produces  the  great  complexity  of  the  adult  organism, 


6  INTRODUCTORY  [CH.  I. 

there  are  certain  cells  which  still  retain  their  primitive  structure ; 
notable  among  these  are  the  white  corpuscles  of  the  blood. 


FIG.  4.— Human  colourless  blood-corpuscle,  showing  its  successive  changes  of  outline  within 
ten  minutes  when  kept  moist  on  a  warm  stage.    (Schofield.) 

It  would  appear  at  first  sight  an  easy  problem  to  distinguish 
between  a  living  thing,  and  one  which  is  not  living.  The  principal 
signs  of  life  are  the  following : — 

1.  Irritability ;  that  is  the  property  of  responding  by  some  change 
under  the  influence  of  an  external  agent  or  stimulus.    The  most  obvious 
of  these  changes  is  movement  (amoeboid  movement,  ciliary  movement, 
muscular  movement,  etc.). 

2.  Power  of  assimilation,  that  is,  ability  to  convert  into  protoplasm 
the  nutrient  material  or  food  which  is  ingested. 

3.  Power  of  growth ;  this  is  a  natural  consequence  of  the  power 
of  assimilation. 

4.  Power  of  reproduction ;  this  is  a  variety  of  growth. 

5.  Power  to  excrete ;  to  give  out  waste  materials,  the  products  of 
other  activities. 

It  should,  however,  be  recognised  that  certain  of  these  five  char- 
acteristics may  be  absent  or  latent,  and  yet  the  object  may  be  living. 
For  instance,  power  of  movement  is  absent  in  many  vegetable  struc- 
tures ;  certain  seeds  and  spores  can  be  dried  and  kept  for  many  years 
in  an  apparently  dead  condition,  and  yet  will  sprout  and  grow  when 
placed  in  appropriate  surroundings. 

Of  all  the  signs  of  life,  those  numbered  2  and  5  in  the  foregoing 
list  are  the  most  essential.  Living  material  is  in  a  continual  state 
of  unstable  chemical  equilibrium,  building  itself  up  on  the  one  hand, 
breaking  down  on  the  other ;  the  term  used  for  the  sum  total  of  these 
intra-molecular  rearrangements  is  metabolism.  The  chemical  sub- 
stances in  the  protoplasm  which  are  the  most  important  from  this 
point  of  view  are  the  complex  nitrogenous  compounds  called  Proteins. 
So  far  as  is  at  present  known,  protein  material  is  never  absent  from 
living  substance,  and  is  never  present  in  any  thing  else  but  that 
which  is  alive  or  has  been  formed  by  the  agency  of  living  cells.  It 
may  therefore  be  stated  that  Protein  Metabolism  is  the  most  essential 
characteristic  of  vitality. 


CHAPTEK   II 


THE   ANIMAL   CELL 

AN  animal  cell  is  usually  of  microscopic  dimensions,  in  the  human 
body  varying  from  ^-J-^  to  ^Vo  °f  an  incn  ^n  diameter. 
It  consists  of — 

1.  Protoplasm.     This  makes  up  the  main  substance  of  the  cell. 

2.  Nucleus:   a  vesicular  body  within  the  protoplasm,  generally 
situated  near  the  centre  of  the  cell. 

3.  Centrosome  and  attraction  sphere:  these  are  contained  within 
the  protoplasm,  near  the  nucleus. 

These  three  portions  demand  separate  study. 

Protoplasm. 

Protoplasm  is  a  soft  jelly-like  material;  it  usually  contains 
minute  particles  or  granules  floating  in  it  which  are  more  solid  in 
consistency,  or  globules  (vacuoles)  containing  a  watery  fluid  may 
be  present.  There  is  considerable  difference 
of  opinion  between  histologists  as  to  whether, 
apart  from  this,  protoplasm  exhibits  any 
structure  or  is  a  homogeneous  jelly.  With 
high  powers  of  the  microscope  it  can,  how- 
ever, be  demonstrated  that  in  many  cells  the 
protoplasm  can  be  differentiated  into  two 
parts,  a  fine  network  of  fibrillae  in  which 
the  more  fluid  and  apparently  structureless 
portion  of  the  protoplasm  is  contained. 
This  view  of  the  structure  of  protoplasm  is 
shown  diagrammatically  in  the  accompanying 
figure  (fig.  5). 

This  theory  of  protoplasmic  structure 
was  advanced  by  Leydig,  and  has  in  more 
recent  years  been  adopted  by  Schafer,  who 
speaks  of  the  network  or  spongework  as  the 
reticulum  or  spongioplasm,  and  the  more  fluid  portion  in  its 
meshes  as  the  enchylema  or  hyaloplasm.  Biitschli,  on  the  other 


FIG.  5.— Diagram  of  an  animal 
cell  consisting  of  fibrillated 
protoplasm,  containing  a 
nucleus. 


8  THE  ANIMAL  CELL  [CH.  II. 

hand,  regards  the  spongioplasm  as  the  optical  effect  of  a  honeycomb 
or  froth -like  structure,  whereas  other  observers  regard  all  such 
appearances  as  artifacts,  that  is,  as  produced  artificially  by  methods 
of  fixing  and  staining.  Hardy,  in  particular,  has  shown  that  a  film 
of  any  colloidal  substance  such  as  gelatin  will,  when  it  "sets," 
present  the  appearance  of  a  network,  and  he  regards  it  as  probable 
that  the  network  seen  in  cells  may  be  due  to  a  similar  setting 
or  coagulation  of  the  protoplasm  which  occurs  either  when  the  cell 
dies  or  is  fixed  by  hardening  reagents.  Schafer,  however,  has  quite 
recently  been  successful  in  obtaining  instantaneous  photographs 
of  white  blood-corpuscles  in  the  living  condition  entirely  untreated 
by  any  reagents,  and  these  distinctly  show  the  presence  of  a  fine 
fibriilar  network  in  the  greater  extent  of  their  protoplasm.  The 
spongioplasm-hyaloplasm  theory  is  therefore  now  in  a  safer  position 
than  it  occupied  previously,  and  the  adoption  of  this  view  renders 
more  intelligible,  as  we  shall  see  later,  the  phenomena  of  proto- 
plasmic movement. 

If  we  adopt  this  hypothesis,  the  granules  seen  in  protoplasm  may 
be  in  part  thickened  portions  of  the  spongioplasm,  but  there  is  no 
doubt  that  the  majority  of  them  are  freely  floating  in  the  protoplasm. 
Some  of  these  are  fatty  in  nature  (staining  black  with  osmic  acid), 
some  are  composed  of  the  substance  called  glycogen  or  animal  starch 
(staining  reddish-brown  with  iodine),  and  sometimes  in  a  few 
unicellular  animals  they  consist  of  inorganic  (calcareous)  matter. 
But  by  far  the  most  constant  and  abundant  of  the  granules  are,  like 
the  main  substance  of  the  protoplasm,  protein  or  albuminous  in 
composition;  by  some  observers  these  protein  granules  are  regarded 
as  essential  constituents  of  the  protoplasm.  Substances  stored 
within  the  protoplasm,  such  as  pigment  granules,  fat  globules, 
fluid  in  vacuoles,  and  glycogen,  are  spoken  of  as  cell-contents  or 
paraplasm. 

The  chemical  structure  of  protoplasm  can  only  be  investigated 
after  the  protoplasm  has  been  killed.  The  substances  it  yields  are 
(1)  Water ;  at  least  three-quarters  of  the  weight,  often  more,  consist 
of  water.  (2)  Proteins.  These  are  the  most  constant  and  abundant 
of  the  solids.  A  protein  or  albuminous  substance  consists  of  carbon, 
hydrogen,  nitrogen,  oxygen,  with  sulphur  and  phosphorus  in  small 
quantities  only.  In  nuclein,  a  complex  material  found  in  the  nuclei 
of  cells,  phosphorus  is  more  abundant.  The  protein  obtained  in 
greatest  abundance  in  the  cell  protoplasm  is  called  a  nucleo-protein  ; 
that  is  to  say,  it  is  a  compound  containing  varying  amounts  of  this 
material  nuclein  with  protein.  White  of  egg  is  a  familiar  instance 
of  an  albuminous  substance  or  protein,  and  the  fact  (which  is  also 
familiar)  that  this  sets  into  a  solid  on  boiling  will  serve  as  a  reminder 
that  the  greater  number  of  the  proteins  found  in  nature  have  a 


CH.  II.] 


THE  NUCLEUS 


similar  tendency  to  coagulate  under  the  influence  of  heat  and  other 
agencies.  (3)  Lipoids.  These  are  so  called  because  they  resemble 
fats  in  their  solubilities ;  they  are  present  usually  only  in  small 
quantities,  and  those  which  most  constantly  occur  are  phosphorised 
fats  (such  as  lecithin)  and  cholesterin,  a  monatomic  alcohol.  (4)  In- 
organic salts,  especially  phosphates  and  chlorides  of  calcium,  sodium, 
and  potassium. 

The  Nucleus. 

In  form  the  nucleus  is  generally  round  or  oval,  but  it  may  have 
in  some  cases  an  irregular  shape,  and  in  other  cases  there  may  be 
more  than  one  nucleus  in  a  cell. 

The  nucleus  exercises  a  controlling  influence  over  the  nutrition 
and  subdivision  of  the  cell ;  any  portion  of  a  cell  cut  off  from  the 
nucleus  undergoes  degenerative  changes. 

A  nucleus  consists  of  four  parts — 

1.  The  nuclear  membrane,  which  encloses  it. 

2.  A  network  of  fibres  in  appearance  like  the  spongioplasm  of  the 

protoplasm,  but  on  a  larger  scale ;  that  is  to  say,  the  threads 
of  which  it  is  composed  are  much  coarser  and  much  more 
readily  seen.  The  name  chromoplasm  has  been  given  to 
this  network. 

3.  The  nuclear  sap   or   matrix,   a    semi-fluid   and   homogeneous 

substance  which  occupies  the  interstices  of  the  spongework 
of  chromoplasm. 

4.  Nucleoli ;  these  are  of  two  principal  varieties ;  some  are  knots 

or  thickened  portions  of  the  network  (pseudo-nucleoli),  and 
others,  the  true  nucleoli,  lie  in  the  nuclear  sap. 

These  four  parts  of  the  .  nucleus  are  represented  in  tha  next 
diagram. 


Node  of  network 


Node  of  network 


— k~  Nuclear  membrane. 
Nucleolus. 

' Nuclear  matrix. 

Nuclear  network. 


FK;.  G. — The  nucleus — diagrammatic.    (Waldeyer.) 


Iii  the  investigation  of  microscopic  objects,  a  histologist  is  nearly 
always  obliged  to  use  staining  agents ;  the  extremely  thin  objects  he 
examines  are  so  transparent  that,  without  such  stains,  much  of  the 


10  THE  ANIMAL  CELL  [CH.  II. 

structure  would  be  invisible.  If  such  dyes  as  haematoxylin  or 
safranin  are  employed,  it  is  the  nucleus  which  becomes  most  deeply 
stained,  and  thus  stands  out  on  the  lighter  background  of  the 
protoplasm. 

But  the  whole  nucleus  does  not  stain  equally  deeply ;  it  is  the 
chromoplasmic  filaments  and  the  nucleoli  which  have  most  affinity  for 
the  stain,  while  the  nuclear  sap  is  comparatively  unaffected.  Hence 
the  terms  chromatin  and  achromatin  originally  introduced  by  Fleming. 
The  membrane,  the  network,  and  the  nucleoli  are  composed  of  chro- 
matic substance  or  chromatin ;  it  is  so  called  not  because  it  has  any 
colour  in  the  natural  state,  but  because  it  has  an  affinity  for  colours 
artificially  added  to  it.  For  a  corresponding  reason,  achromatin  or 
achromatic  substance  is  the  name  given  to  the 
substances  which  make  up  the  nuclear  sap. 

Balbiani  showed  that  the  chromoplasmic  filaments  are 
apparently  transversely  marked  into  alternate  dark  and  light 
bands ;  this  is  due  to  the  existence  of  minute  highly  refracting 
particles  imbedded  in  regular  series  in  a  clear  homogeneous 
and  unstainable  matrix  (see  fig.  7).  The  term  chromatin  should 
properly  be  restricted  to  these  particles.  These  particles  have 
special  affinity  for  basic  dyes,  such  as  methylene  blue  and 
safranin. 

Coming  next  to  the  chemical  composition  of  the 
nucleus,  it  is  found  to  consist  principally  of  protein 
°ma*  and  protein-like   substances.     The   nuclei   of   cells 
ment,  greatly  magni-  may  \)Q   obtained   by   subjecting  the   cells   to   the 

tied.    (Oarnoy.)  *  p         i  •«    •    -i  i    •       •    •  it  j       i 

action  of  artificial  gastric  juice;  the  protoplasm  is 
nearly  entirely  dissolved,  but  the  nuclei  resist  the  solvent  action  of 
the  juice.  No  doubt  the  nuclei  contain  several  chemical  compounds, 
but  the  only  one  of  which  we  have  any  accurate  knowledge  has 
been  termed  nuclein,  and  this  is  identical  with  the  substance  called 
chromatin  by  histologists.  It  is  soluble  in  alkalis,,  but  precipitated 
by  acids;  it  is  different  from  a  simple  protein,  as  it  contains  in  addi- 
tion to  carbon,  nitrogen,  oxygen,  hydrogen,  and  sulphur,  a  large 
quantity  (7  to  8  per  cent,  or  even  more)  of  phosphorus  in  its 
molecule.  In  many  cases  nucleins  contain  iron  also. 


The  Attraction  Sphere. 

In  addition  to  the  nucleus  and  protoplasm,  all  living  cells 
contain  another  structure,  namely,  a  minute  particle  called  a 
"  centrosome"  which  has  an  attractive  influence  on  protoplasmic 
fibrils  and  granules  in  its  neighbourhood,  the  whole  appear- 
ance produced  being  called  an  attraction  sphere  (fig.  8). 

It   is  most  prominent   in  cells  which  are  dividing  or   about  to 


CH.  II.] 


PROTOPLASMIC   MOVEMENT 


11 


divide.     The  centrosome,   and  then   the   attraction   sphere,  become 
double  (fig.  9).     In  all  probability  the  centrosome  gives  the  primary 


FIG.  8. — A  cell  (semi-diagrammatic) 
showing  its  attraction  sphere. 
In  this,  as  in  most  cases,  the 
attraction  sphere  lies  near  the 
nucleus.  (Schafer.) 


FIG.  9. — Ovum  of  the  worm  Ascaris, 
showing  a  twin  attraction  sphere. 
The  nucleus  with  its  contorted 
filament  of  chromoplasm  is  repre- 
sented, but  the  protoplasm  of 
the  cell  is  not  filled  in.  (v. 
Beneden.) 


impulse  to  cell-division.     Some  cells,  for  instance,  the  giant  cells  of 
red  marrow,  contain  numerous  centrosomes. 


Protoplasmic  Movement. 

A  cell  possesses  the  power  of  breathing,  that  is,  taking  in  oxygen ; 
of  nutrition,  of  building  itself  up  from  food  materials ;  and  of  excre- 
tion, or  the  getting  rid  of  waste  material.  But  the  most  obvious 
characteristic  of  most  cells  is  their  power  of  movement. 

When  an  amoeba  is  observed  with  a  high  power  of  the  micro- 
scope, it  is  found  to  consist  of  an  irregular  mass  of  protoplasm  con- 
taining one  or  more  nuclei,  the  proto- 
plasm itself  being  more  or  less  granular 
and  vacuolated.  If  watched  for  a  minute 
or  two,  an  irregular  projection  is  seen  to 
be  gradually  thrust  out  from  the  main 
body  and  retracted;  a  second  mass  is 
then  protruded  in  another  direction,  and 
gradually  the  whole  protoplasmic  sub- 
stance is,  as  it  were,  drawn  into  it.  The 
Amoeba  thus  comes  to  occupy  a  new  position,  and  when  this  is 
repeated  several  times  we  have  locomotion  in  a  definite  direction, 
together  with  a  continual  change  of  form.  These  movements,  when 
observed  in  other  cells,  such  as  the  colourless  blood-corpuscles  of 
higher  animals  (fig.  11),  in  the  branched  cells  of  the  cornea  and 
elsewhere,  are  hence  termed  amoeboid.  The  projections  which  are 
alternately  protruded  and  retracted  are  called  pseudopodia. 


FIG.  10. — Amoebae. 


12 


THE  ANIMAL  CELL 


[GIL  II. 


A  streaming  movement  is  not  infrequently  seen  in  certain  of 
the  protozoa,  in  which  the  mass  of  protoplasm  extends  long  and 
fine  processes,  themselves  very  little  movable,  but  upon  the  surface 


FIG    11.— Human  colourless  blood-corpuscle,  showing  its  successive  changes  of  outline  within  ten 
minutes  when  kept  moist  on  a  warm  stage.    (Schofield.) 

of  which  freely-moving  or  streaming  granules  are  seen.  A  gliding 
movement  has  also  been  noticed  in  certain  animal  cells ;  the  motile 
part  of  the  cell  is  composed  of  protoplasm  bounding  a  central  mass ; 
by  means  of  the  free  movement  of  this  layer,  the  cell  may  be 
observed  to  move  along. 


FIG.  12.— (A)    Young  vegetable  cells,  showing  cell-cavity  entirely  filled  with  granular  protoplasm 

enclosing  a  large  oval  nucleus,  with  one  or  more  nucleoli. 

(B)   Older  cells  from  same  plant,  showing  distinct  cellulose-wall  and  vacuolation  of  proto- 
plasm. 

In  vegetable  cells  the  protoplasmic  movement  can  be  well  seen 
in  the  hairs  of  the  stinging-nettle  and  Tradescantia  and  the  cells  of 

Vallisneria  and  Chara ;  it  is  marked 
by  the  movement  of  the  granules 
nearly  always  imbedded  in  it.  For 
example,  if  part  of  a  hair  of  Trade- 
scantia (fig.  13)  is  viewed  under  a 
high  magnifying  power,  streams  of 
protoplasm  containing  crowds  of 
granules  hurrying  along,  like  the 
foot-passengers  in  a  busy  street, 
are  seen  flowing  steadily  in  definite 
directions,  some  coursing  round  the 
film  which  lines  the  interior  of 
the  cell-wall,  and  others  flowing 
towards  or  away  from  the  irregular 
mass  in  the  centre  of  the  cell-cavity.  Many  of  these  streams  of 
protoplasm  run  together  into  larger  ones  and  are  lost  in  the 


FIG.  13. — Cell  of  Tradescantia  drawn  at  suc- 
cessive intervals  of  two  minutes. — The  cell- 
contents  consist  of  a  central  mass  connected 
by  many  irregular  processes  to  a  peripheral 
Him,  the  whole  forming  a  yacuolated  mass 
of  protoplasm,  which  is  continually  changing 
its  shape.  (Schofield.) 


en.  n. ] 


IRRITABILITY  OF  PROTOPLASM 


13 


central  mass,  and  thus  ceaseless  variations  of  form  are  produced. 
The  movement  of  the  protoplasmic  granules  to  or  from  the  peri- 
phery is  called  circulation,  whereas  the  movement  of  the  protoplasm 
round  the  interior  of  the  cell  is  called  rotation. 

The  first  account  of  the  movement  of  protoplasm  was  given  by 
Kdsel  in  1755,  as  occurring  in  a  small 
Proteus,  probably  a  large  freshwater 
amoeba.  His  description  was  followed 
twenty  years  later  by  Corti's  demonstra- 
tion of  the  rotation  of  the  cell  sap  in 
Characese,  and  in  the  earlier  part  of  last 
century  by  Meyer  in  Yallisneria,  1827, 
and  by  Eobert  Brown,  1831,  in  "  Staminal 
Hairs  of  Tradescantia."  Then  came  Du- 
jardin's  description  of  the  granular  stream- 
ing in  the  pseudopodia  of  Ehizopods; 
movements  in  other  animal  cells  were 
described  somewhat  later  (Planarian  eggs, 
v.  Siebold,  1841 ;  colourless  blood-cor- 
puscles, Wharton  Jones,  1846). 

There  is  no  doubt  that  protoplasmic 
movement  is  essentially  the  same  thing 
in  both  animal  and  vegetable  cells.  But 
in  vegetable  cells  the  cell-wall  obliges 
the  movement  to  occur  in  the  interior, 
while  in  the  naked  animal  cells  the  move- 
ment results  in  an  external  change  of 
form. 

Although  the  movements  of  amoeboid  cells  may  be  loosely  de- 
scribed as  spontaneous,  yet  they  are  produced  and  increased  under 
the  action  of  external  agencies  which  excite  them,  and  which  are 
therefore  called  stimuli,  and  if  the  movement  has  ceased  for  the  time, 
as  is  the  case  if  the  temperature  is  lowered  beyond  a  certain  point, 
movement  may  be  set  up  by  raising  the  temperature.  Again,  contact 
with  foreign  bodies,  gentle  pressure,  certain  salts,  and  electricity, 
produce  or  increase  the  movement  in  the  amoeba.  The  protoplasm 
is,  therefore,  sensitive  or  irritable  to  stimuli,  and  shows  its  irritability 
by  movement  or  contraction  of  its  mass.  The  effects  of  some  of 
these  stimuli  may  be  thus  further  detailed : — 

a.  Changes  of  temperature. — Moderate  heat  acts  as  a  stimulant : 
the  movement  stops  when  the  temperature  is  lowered  near  the 
freezing-point  or  raised  above  45°  C.  (113°  F.);  between  these  two 
points  the  movements  increase  in  activity ;  the  optimum  temperature 
is  about  37°  to  38°  C.  Though  cold  stops  the  movement  of  proto- 
plasm, exposure  to  a  temperature  even  below  0°  C.  does  not  prevent 


FIG.  14.— Cells  from  the  staminal 
hairs  of  Tradescantia.  A,  fresli 
in  water ;  B,  the  same  cell  after 
slight  electrical  stimulation ; 
a,  ft,  region  of  stimulation ; 
c,  d,  clumps  and  knobs  of  con- 
tracted protoplasm.  (Kiihne.) 


14  THE   ANIMAL   CELL  [CH.  II. 

its  reappearance  if  the  temperature  is  raised;  on  the  other  hand, 
prolonged  exposure  to  a  temperature  of  42°-45°  C.  altogether  kills  the 
protoplasm  and  causes  it  to  enter  into  a  condition  of  heat  rigor. 
This  is  due  to  the  coagulation  of  the  proteins  present. 

b.  Chemical  stimuli. — Distilled  water  first  stimulates  then  stops 
amoeboid  movement,  for  by  imbibition  it  causes  great  swelling  and 
finally  bursting  of  the  cells.  In  some  cases,  however  (myxomycetes), 
protoplasm  can  be  almost  entirely  dried  up,  but  remains  capable  of 
renewing  its  movement  when  again  moistened.  Dilute  salt  solution 
and  very  dilute  alkalis  stimulate  the  movements  temporarily.  Acids 
or  strong  alkalis  permanently  stop  the  movements :  ether,  chloroform, 
veratrine  and  quinine  also  stop  it  for  a  time. 

Movement  is  suspended  in  an  atmosphere  of  hydrogen  or  carbonic 
acid,  and  resumed  on  the  admission  of  air  or  oxygen ;  complete  with- 
drawal of  oxygen  will  after  a  time  kill  protoplasm. 

c.  Electrical. — Weak  currents  stimulate  the 

movement,   while    strong    currents    cause    the 

cells  to  assume  a  spherical  form  and  to  become 

motionless. 

The  amosboid  movements  of  the  colourless 

corpuscles  of   the  blood  may  be   readily  seen 

FIG.  15.-An  ameboid  cor-      ^6n    a    dr°P,  °f .  bl°°d    fr°m    the  fing6r  is  mixed 

puscie  of  the  newt  killed    with   salt   solution,   and  examined  on  a  warm 

by  instantaneous  apph-         ,  «ji      ,1  •  TO  t  i  • 

cation  of  steam,  show-    stage  with  the  microscope.     If  a  pseudopodium 

the  pswdopodfarai(Af ter    °f  sucn  a  corpuscle  is   observed  under  a  high 

schafer,  "  Quain's  Ana-    power,  it  will  be  seen  to  consist  of  hyaloplasm, 

which  has  flowed  out  of  its  spongy  home,  the 

reticulum.     Later,  however,  a  portion  of  the  reticular  part  of   the 

protoplasm  may  enter  the  pseudopodium.     The  cells  may  be  fixed 

by  a  jet  of  steam  allowed  to  play  for  a  moment   on  the   surface 

of  the  cover  glass.     Fig.  15  illustrates  one  fixed  in  this  way. 

If,  therefore,  we  adopt  Schiifer's  views  on  the  structure  of 
protoplasm  we  see  that  the  essential  act  in  the  protrusion  of  a 
pseudopodium  is  the  flowing  of  the  hyaloplasm  out  of  the  spongio- 
plasm; the  retraction  of  the  pseudopodium  is  a  return  of  the 
hyaloplasm  to  the  spongioplasm.  The  spongioplasm  has  an  irregular 
arrangement  with  openings  in  all  directions,  so  that  the  contractility 
of  undifferentiated  cells  may  exhibit  itself  towards  any  point  of  the 
compass. 

The  relation  of  cells  to  various  forms  of  stimulus  has  been  recently  very 
extensively  studied.  Various  forms  of  unicellular  organisms  have  been  used  in 
these  experiments,  and  the  stimuli  employed  have  been  chemical,  thermal,  light, 
electric  currents,  and  so  forth.  If  the  cell  moves  towards  the  source  of  attraction, 
the  term  positive  taxis  is  employed ;  if  it  is  repelled,  negative  taxis.  The  words, 
chemo-taxis,  thermo-taxis,  photo-taxis,  galvano-taxis,  etc.,  indicate  the  kind  of 
stimulus!  nvestigated. 


CH.  II. J  CELL  DIVISION  15 

Cell  Division. 

A  cell  multiplies  by  dividing  into  two;  each  remains  awhile 
in  the  non-dividing  condition,  but  later  it  grows  and  subdivides,  and 
the  process  may  be  repeated  indefinitely. 

The  supreme  importance  of  the  cell,  the  growth  of  the  body  from 
cells,  and  the  fact  that  cells  are  the  living  units  of  the  organism, 
were  first  established  in  the  vegetable  world  by  Schleiden,  and 
extended  to  the  animal  kingdom  by  Theodor  Schwann.  The  ideas 
of  physiologists  depending  on  this  idea  are  grouped  together  as 
cellular  physiology,  which  under  the  guidance  of  Virchow  was  ex- 
tended to  pathology  also:  Virchow  expressed  the  doctrine  now  so 
familiar  as  to  be  almost  a  truism  in  the  terse  phrase  omnis  cellula  e 
cellula  (every  cell  from  a  cell). 

The  division  of  a  cell  is  preceded  by  division  of  its  nucleus. 
Nuclear  division  may  be  either  (1)  simple  or  direct,  which  consists  in 
the  simple  exact  division  of  the  nucleus  into  two  equal  parts  by  con- 
striction in  the  centre,  which  may  have  been  preceded  by  division  of 
the  nucleolus ;  or  (2)  indirect,  which  consists  in  a  series  of  changes 
which  goes  on  in  the  arrangement  of  the  nuclear  reticulum,  resulting 
in  the  exact  division  of  the  chromatic  fibres  into  two  parts,  which 
form  the  chromoplasm  of  the  daughter  nuclei. 

The  changes  in  the  nucleus  during  indirect  division  constitute 
karyokinesis  (Kapvov,  a  kernel),  or  mitosis  OU/TO?,  a  thread),  and 
direct  division  is  called  amitotic  or  akinetic  (Kivya-is,  movement).  It 
is  now  believed  that  the  mitotic  nuclear  division  is  all  but,  though 
not  quite,  universal.  Somewhat  different  accounts  of  the  stages  of 
the  nuclear  division  have  been  given  by  different  authorities,  accord- 
ing to  the  kind  of  cell  in  which  the  nuclear  changes  have  been 
studied ;  but,  speaking  generally,  the  process  may  be  divided  into  the 
following  stages : — 

1.  The  non-dividing  nucleus  (fig.  16). 


Node  of  network  — ^    ,.   . .....     ,    ,^ 

_.„*-.  Nuclear  membrane. 

.Nucleolus. 

Node  of  network l-^^^^p^xfC^T^-^- Nuclear  matrix. 

( Nuclear  network. 

FIG.  16.— The  non-dividing  nucleus.    (Waldeyer.) 

2.  The   spirem   or  skein  stage :    the  nucleoli   dissolve,   and   the 
nuclear  filaments  form  loops  which  run  from  one  pole  of  the  nucleus 


16 


THE  ANIMAL   CELL 


[CH.  II. 


to  the  other  (fig.  17).  In  some  cells  there  is  at  first  one  long, 
much  twisted  thread,  which  subsequently  breaks  up  into  segments. 
The  loops  are  called  chromosomes. 

3.  Each  loop   becomes  less  convo- 
luted and  splits  longitudinally  into  two 
sister     threads,    and     the    achromatic 
spindle  appears  (fig.  18,  A  and  B). 

4.  The  equatorial  stage;  monaster. 
The  nucleus  has  now  two  poles,  those 
of  the  spindle ;  and  at  each  pole  there 
is    a    polar    corpuscle    or    centrosome. 
The  division  of  the  centrosome  of  the 
original  cell,  and  then  of  the  attraction 
sphere  into  two,  usually  precedes  the 

commencement  of  changes  in  the  nucleus ;  the  two  attraction  spheres 
become  prominent  in  cell  division,  and  the  connecting  achromatic 


FIG.  17.— Early  condition  of  the  skein 
stage  vie  wed  at  the  polar  end.  l.c.f., 
Looped  chromatic  filament ;  i.f.,  irre- 
gular filament.  (Rabl.) 


Achromatic  spindle  — --x?-— 


FIG.  18. — Later  condition  of  the  skein  stage  in  karyokinesis.  A,  The  chromosomes  become  less  cor- 
voluted  and  the  achromatic  spindle  appears.  B,  The  chropnosomes  split  into  two  and  the  ac'h^o. 
matic  spindle  becomes  longitudinal.  (Waldeyer.) 

spindle  is  probably  also  formed  from  them  or  from  the  achromatic 
material  of  the  nucleus. 

At    this    stage    the    nuclear  Pole  of  spmni 


Outer  granular 

zone. 


— .  Split  fibres. 


Inner  clear  zone. 


- Polar  corpuscle. 


FIG.  19. — Monaster  stage  of  karyokinesis. 
(Waldeyer.) 


membrane  is  lost,  and  thus  cell 
protoplasm  and  nuclear  sap 
become  continuous;  the  proto- 
plasmic granules  are  arranged 
radially  from  the  polar  corpuscles. 
The  star-like  arrangement  of 
these  granules  is  much  better 
marked  in  embryonic  cells,  indeed 
the  lines  present  very  much  the 
appearance  of  fibrils  (see  fig.  20). 
The  V -snaPed  chromosomes 
sink  to  the  equator  of  the 
spindle,  and  arrange  themselves 
from  it. 


so    as   to    project    horizontally 


CH.  II.] 


KARYOKINESIS 


17 


Polar  circle 


Medullary 


In  cells  which  are  the  result  of  the  sexual  process,  the  number 
of  chromosomes  is  always  even,  an  equal  number  being  contributed 
by  each  sex. 

The  number  of  chromosomes  varies  with  the  species  from  four 
to  twenty-four;   in  man   the 
number  is  sixteen. 

5.  The  stage  of  metakinesis. 
The   sister   threads   separate, 
one    set  going   towards    one 
pole,   and   the   other   to    the 
other    pole    of    the    spindle 
(fig.  21):  these  form  the  two 
daughter  nuclei.    The  chromo- 
somes are  probably  pulled  into 
their  new  position  by  the  con- 
traction of  the  spindle  fibres 
attached  to  them. 

6.  Each  daughter  nucleus 
goes   backwards  through  the 
same  series  of  changes;   the 

diaster  or  double  star  is  followed  by  the  dispirem  or  double  skein, 
until  at  last  two  resting  nuclei  are  obtained  (fig.  22). 

A  new  membrane  forms  around  each  daughter  nucleus,  the  spindle 
atrophies,  and  the  attraction  sphere  becomes  less  prominent.  The 


Attraction 
sphere 


Pole-body 


Antipodal  zone 


FIG.  20. — Ovum  of  the  worm  Ascaris  in  process  of  divi- 
sion. The  attraction  spheres  are  at  opposite  ends 
of  the  ovum  ;  at  the  equator  of  the  spindle  which 
unites  them,  four  chromosomes  are  seen.  The  proto- 
plasm of  the  ovum,  except  in  the  equatorial  zone  of 
the  cell,  is  arranged  in  lines  radiating  from  the  centre 
(centrosome)  of  the  attraction  sphere.  (Waldeyer.) 


. . Fine  uniting 

filaments. 


Fio.  21. — Metakinesis.    A,  Early  stage.     B,  Later  stage,    c,  Latest  stage — formation  of  diaster.     A  and 
B  show  how  the  sister  threads  disentangle  themselves  from  one  another.    (Waldeyer.) 

division  of  the  protoplasm  into  two  parts  around  the  nuclei  begins 
in  the  diaster  stage,  and  is  complete  in  the  stage  represented  in 
fig.  22. 

The  karyokinetic  process  has  been  watched  in  all  its  stages  by 
more  than  one  observer.  The  time  occupied  varies  from  half  an  hour 
to  three  hours ;  the  details,  however,  must  be  studied  in  hardened 
and  appropriately  stained  specimens.  They  are  most  readily  seen 
in  cells  with  large  nuclei,  such  as  occur  in  the  epidermis  of 

B 


18 

amphibians,  in  the 
of  plants. 


THE  ANIMAL  CELL  [CH.  II. 

cells  of  certain  worms,  or  in  the  growing  tips 


Remains  of  spindle. 


Line  of  separation  of  the 

two  cells. 
Antipole     of     daughter 

nucleus. 


Lighter  substance  of  the 

nucleus. 


Cell  protoplasm. 
--  Hilus. 


Fie.  22.— Final  stages  of  karyokinesis.    In  the  lower  daughter  nucleus  the  changes  are  still  more 
advanced  than  in  the  upper.    (Waldeyer.) 

The  phases  may  be  summarised  in  a  tabular  way  as  follows : — 

1.  Resting    condition    of   mother    nucleus 

(fig.  16). 
f  2.  Close  skein  of  fine  convoluted  filaments 

(fig.  17). 

|  3.  Open  skein  of  thicker  filaments.    Spindle 
[        appears  (fig.  18  A). 

4.  Movement  of    V-shaped    chromosomes 

to  middle  of  nucleus,  and  each  splits 
into  two  sister  threads  (fig.  18  B). 

5.  Stellate  arrangement  of  V  filaments  at 

equator  of  spindle  (fig.  19). 

6.  Separation  of  cleft  filaments  and  move- 

ment along  fibres  of  spindle  (fig.  21  A 
and  B). 

7.  Conveyance  of  V  filaments  towards  poles 

of  spindle  (fig.  21  c). 
r  8.  Open  skein  in  daughter  nuclei. 
1 9.  Close  skein  in  daughter  nuclei  (fig.  22). 
.     10.  Resting  condition    of   daughter    nuclei 
(fig.  22). 

The  Ovum. 

The  ovary  (see  Chapter  LIX.)  is  an  organ  which  produces  ova. 
An  ovum  is  a  simple  animal  cell ;  its  parts  are  seen  in  the  next  diagram. 

It  is  enclosed  in  a  membrane  called  the  zona  pellucida.  The  body 
of  the  cell  is  composed  of  protoplasm  loaded  with  granules  of  food 
material,  called  the  yolk  or  vitellus.  The  nucleus  and  nucleolus  are 
sometimes  still  called  by  their  old  names,  germinal  vesicle  and 
germinal  spot  respectively.  The  attraction  sphere  is  not  shown  in  the 
diagram. 

The  ovum  first  discharges  from  its  interior  a  portion  of  its 
nucleus,  which  forms  two  little  globules  upon  it  called  the  polar 
globules. 


NETWORK  OR  RETICULUM  . 

SKEIN  OR  SPIREM 
CLEAVAGE  .... 

STAR  OR  MONASTER   . 
DIVERGENCE  OR  METAKINESIS 

DOUBLE  STAR  OR  Di ASTER 

DOUBLE  SKEIN  OR  DISPIREM 
NETWORK  OR  RETICULUM  . 


CH.  IL] 


THE  OVUM 


19 


Fertilisation  then  occurs ;  that  is  to  say,  the  head  or  nucleus  of 
a  male  cell  called  a  spermatozoon  penetrates  into  the  ovum,  and 
becomes  fused  with  the  remains  of  the  female  nucleus. 


Nucleus  or  germinal  vesicle. 
~,v^ Nucleolus  or  germinal  spot. 

Space   left  by  retraction  of 
protoplasm. 

Protoplasm  containing  yolk 
spherules. 


Zona  pellucida. 


FIG.  23.— Representation  of  a  human  ovum.    (Cadiat.) 

Cell  division  or  segmentation  then  begins,  and  the  early  stages 
are  represented  in  the  next  figure. 


FIG.  24.— Diagram  of  an  ovum  (a)  undergoing  segmentation.  In  (b)  it  has  divided  into  two,  in  (c)  into 
four;  and  in  (d)  the  process  has  resulted  in  the  production  of  the  so-called  "mulberry-mass." 
(Frey.) 

Fluid  discharged  from  the  cells  accumulates  within  the  interior 
of  the  mulberry  mass  seen  in  fig.  24  d,  and  later,  if  a  section  is  cut 
through  it,  the  cells  will  be  found  arranged  in  three  layers. 

The  outermost  layer  is  called  the  epiblast.  The  middle  layer  is 
called  the  mesoblast.  The  innermost  layer  is  called  the  hypoblast. 

From  these  three  layers  the  growth  of  the  rest  of  the  body  occurs, 
nutritive  material  being  derived  from  the  mother  in  mammals  by 
means  of  an  organ  called  the  placenta. 

The  epiblast  forms  the  epidermis,  the  outermost  layer  of  the 
adult.  It  also  forms  the  nervous/system. 

The  hypoblast,  the  innermost  layer  of  the  embryo,  forms  the 
lining  epithelium  of  the  alimentary  (except  that  of  the  mouth  and 
anus,  which  are  involutions  from  the  epiblast)  and  respiratory  tracts, 
that  is,  the  innermost  layer  Of  the  adult.  It  also  forms  the  cellular 
elements  in  the  large  digestive  glands,  such  as  the  liver  and  pancreas, 
which  are  originally,  like  the  lungs,  outgrowths  from  the  primitive 
digestive  tube. 

The  mesoblast  forms  the  remainder,  that  is,  the  great  bulk  of  the 
body,  including  the  muscular,  osseous,  and  other  connective  tissues  ; 
the  circulatory  and  urino-genital  system* 


CHAPTER  III 

EPITHELIUM 

WE  have  seen  in  the  introductory  chapter  that  the  elementary 
tissues  of  which  the  organs  of  the  body  are  built  up  may  be  arranged 
into  four  groups :  epithelial,  connective,  muscular,  and  nervous.  The 
first  of  these,  the  epithelial  tissues,  follows  naturally  on  a  study  of 
the  animal  cell,  as  an  epithelium  may  be  defined  as  a  tissue  com- 


Fio.  25.— From  a  section  of  the  lung  of  a  cat,  stained  with  silver  nitrate.  N.  Alveoli  or  air-cells, 
lined  with  large  flat,  nucleated  cells,  with  some  smaller  polyhedral  nucleated  cells.  (Klein  and 
Noble  Smith.) 

posed  entirely  of  cells  united  by  a  minimal  amount  of  cementing 
material.  As  a  rule,  an  epithelium  is  spread  out  as  a  membrane, 
covering  a  surface  or  lining  the  cavity  of  a  hollow  organ. 

Epithelia  may  be  grouped  into  two  great  classes,  each  of  which 
may  be  again  subdivided  according  to  the  shape  and  arrangement  of 
the  cells  of  which  it  is  composed. 

20 


GIL  IIL] 


EPITHELIUM 


21 


CLASS  1. — Simple  epithelium;  that  is,  an  epithelium  consisting 
of  only  one  layer  of  cells.     Its  subgroups  are  :— 

a.  Pavement  epithelium.     This  consists  of  a  layer  of  thin  cells 
arranged  in  the  form  of  an  accurately  fitting  mosaic ;  this  is  typically 
seen  in  the  epithelium  that  lines  the  air-sacs  of  the  lungs  (fig.  25). 
The  endothelium  found  in  the  interior  of 
the  blood  and  lymph  vessels  and  serous 
sacs   is   very   similar   in   structure,  but 
differs  from  other  epithelia  in  being  the 
only  one  of  mesoblastic  origin  (fig.  26). 

b.  ^Cubical  and  columnar  epithelium. 
Here  the  cells,  as  their  names  imply,  are 
thicker.     Cubical  epithelium  is  found  in 
the  alveoli  of  the  thyroid,  in  the  tubules 
of  the  testis,  and  in  the  ducts  of  many 
glands.     Columnar  epithelium  lines  the 
alimentary  canal   from  the  stomach   to 
the  anus. 

The  four  figures  (figs.  27-30)  present 
the  very  typical  columnar  cells,  each 
with  a  bright  striated  border,  which 
are  found  lining  the  intestine.  Fig.  28 
shows  how  they  are  arranged  on  the 
surface  of  a  villus,  one  of  the  numerous 
little  projections  found  in  the  small  in- 
testine. The  gaps  seen  there  are  due  to 
the  formation  of  what  are  called  goblet 
cells.  In  some  of  the  columnar  cells  a 
formation  of  granules  occurs ;  these  con- 
sist of  a  substance  called  mucigen ;  these 
run  together  and  are  discharged  from  the 
cell  as  a  brightly  refracting  globule  of 
mucin,  leaving  the  cell  with  open  mouth 
like  a  goblet,  the  nucleus  being  sur- 
rounded by  the  remains  of  the  protoplasm  in  the  narrow  stem 
(fig.  30).  This  transformation  is  a  normal  process  continually  going 
on  throughout  life,  the  discharged  mucin  being  the  chief  constituent 
of  phlegm  or  mucus.  The  cells  themselves  may  recover  their  original 
shape  after  discharge  and  repeat  the  process  later  on. 

c.  Ciliated  epithelium  ;  this  form  of  epithelium  presents  so  many 
points  of   physiological  interest,  that   a   separate   section   will   be 
devoted  to  it  later  in  this  chapter. 

CLASS  2. — Compound  ^Epithelium;   that   is,  an  epithelium   con- 
sisting of  more  than  one  layer  of  cells.     It  contains  two  subgroups, 
a.  Transitional  epithelium  found  lining  the  bladder  and  ureters. 


FIG.  26. — Surface  view  of  an  artery  from 
the  mesentery  of  a  frog,  ensheathed 
in  a  peri  vascular  lymphatic  vessel, 
a,  The  artery,  with  its  circular 
muscular  coat  (media)  indicated  by 
broad  transverse  markings,  with 
an  indication  of  the  adventitia  out- 
side. I,  Lymphatic  vessel ;  its  Avail 
is  a  simple  endothelial  membrane. 
(Klein  and  Noble  Smith.) 


22 


EPITHELIUM 


[CH.  III. 


It  consists  of  three  or  four  layers  of  large  cells,  the  most  typical  of 
which  are  pear-shaped  (fig.  31). 


FIG.  27. — Columnar  epithelium  cells  of  the  rabbit's 
intestine.  The  cells  have  been  isolated  after 
maceration  in  very  weak  chromic  acid.  The 
cells  are  much  vacuolated,  arid  one  of  them 
has  a  fat  globule  near  its  attached  end.  The 
striated  border  (sir.")  is  well  seen,  and  the 
bright  disc  separating  it  from  the  cell  proto- 
plasm, n,  nucleus  with  intra-nuclear  net- 
work; a,  a  thinned-out  winglike  projection 
of  the  cell  which  probably  fitted  between  two 
adjacent  cells.  (Schafer.) 


FIG.  28.— Vertical  section  of  an  intestinal  villus 
of  a  cat.  a,  The  striated  border  of  the  epi- 
thelium ;  b,  columnar  epithelium ;  c,  goblet 
cells  ;  d,  central  lymph-vessel ;  c,  unstriped 
muscular  fibres ;  /,  adenoid  stroma  of  the 
villus  in  which  are  contained  lymph-cor- 
puscles. (Klein.) 


FIG.  29. — A  row  of  columnar  cells  from  the 
rabbit's  intestine.  Smaller  cells  are  seen 
between  the  epithelium  cells ;  these  are 
lymph-corpuscles.  (Schiifer.) 


FIG.  30.— Goblet  cells.    (Klein.) 


FIG.  31.— Epithelium  of  the  bladder,  a,  One  of  the  cells  of 
the  first  row ;  b,  a  cell  of  the  second  row  ;  c,  cells  in  situ, 
of  first,  second,  and  deepest  layers.  (Obersteiner.) 

&.  Stratified  epithelium.     Here  the  cells  are  arranged  in  numerous 
layers.     It  is  found  composing  the  epidermis,  and  the  linings  of  the 


CH.  III.] 


CILIATED    EPITHELIUM 


23 


various  orifices  of  the  body.  It  lines  the  upper  end  of  the  alimentary 
canal  from  the  mouth  to  the  point  where  the  oesophagus  or  gullet 
enters  the  stomach.  The  deepest  layers  are  columnar  or  cubical  in 
shape,  and  the  surface  layers  are  composed  of  flattened  scales,  their 


Fio.  32.— Vertical  section  of  the  stratified  epithelium  of  the  rabbit's  cornea,  a,  Anterior  epithelium, 
showing  the  different  shapes  of  the  cells  at  various  depths  from  the  free  surface ;  &,  a  portion  of  the 
substance  of  cornea.  (Klein.) 

protoplasm  being  replaced  by  horny  material  or  keratin.  Covering 
the  front  of  the  cornea  of  the  eye  is  a  typical  form  of  stratified 
epithelium  (fig.  32),  but  the  number  of  layers  is  not  so  great  as  it  is 
in  the  majority  of  such  epithelia. 


Ciliated  Epithelium. 

The  cells  of  ciliated  epithelium  are  generally  of  columnar  shape 
(fig.  33),  but  they  may  occasionally  be  spheroidal  (fig.  34). 


FIG.  33.— Ciliated  epithelium  from  the  human 
trachea,  a,  Large  fully-formed  cell ;  6, 
shorter  cell ;  c,  developing  cells  with  more 
than  one  nucleus.  (Cadiat.) 


Fia.  34.— Spheroidal  ciliated 
cells  from  the  mouth  of 
the  frog,  x  800  diame- 
ters. (Sharpey.) 


Each  cell  is  surmounted  by  a  bunch  of  fine  tapering  filaments. 
They  were  originally  called  cilia  because  of  their  resemblance  in  shape 
to  eyelashes.  They  differ  from  eyelashes  in  being  extremely  small, 


24 


EPITHELIUM 


[CH.  IIL 


and  in  not  being  stiff;    they  are  in  fact  composed  of   protoplasm. 

During  life  these  move   to   and   fro,  and  so  produce  a  current  of 

fluid  over  the  surface  they  cover. 
Like  columnar  cells,  they  may 
form  goblet  cells  and  discharge 
mucin. 

In  the  larger  ciliated  cells,  it 
will  be  seen  that  the  border  on 
which  the  cilia  are  set  is  bright, 
and  composed  of  little  knobs,  to 
each  of  which  a  cilium  is  at- 
tached ;  in  some  cases  the  knobs  are 
prolonged  into 

the    Cell 


.    35.  —  Ciliated    epithelium    of    the    human 

trachea.     a,  Layer  of  longitudinally  arranged  •.                          c  , 

elastic  fibres;    b,    basement    membrane;    c,  plaSHl     as     Ella- 

deepest    cells,  circular    in    form;    d>    inter-  ma^fc,    ^^  vr^f 

mediate  elongated  cells;   e,  outermost  layer  mt;Llljb    Ol  1 

of  cells  fully  developed   and    bearing  cilia,  let  8      (fig.       36). 

According      to 

some  observers  these  rootlets  are  outgrowths  from 
the  multiplied  centrosome  of  the  cell. 

The  bunch  of  cilia  is  homologous  with  the 
striated  border  of  columnar  cells. 

Ciliated  epithelium  is  found  in  the  human 
body,  (1)  lining  the  air  passages,  but  not  in  the 
alveoli  of  the  lungs  ;  these  are  lined  by  pavement 
epithelium  ;  (2)  in  the  Fallopian  tubes  and  upper 
part  of  the  uterus  ;  (3)  in  the  ducts  of  the  testis 
known  as  the  vasa  efferentia  and  coni  vasculosi  ; 
here  the  cilia  are  the  longest  found  in  the  body  ; 
(4)  in  the  ventricles  of  the  brain  and  central 
canal  of  the  spinal  cord  ;  (5)  the  tail  of  a  sperma- 
tozoon may  also  be  regarded  as  a  long  cilium. 

In  other  animals  cilia  are  found  in  other 
parts;  for  instance,  in  the  frog  the  mouth  and 
gullet  are  lined  by  ciliated  cells  ;  in  the  tadpole, 
the  whole  surface  of  the  body  and  especially  the 
gills  are  covered  with  cilia.  Among  the  inverte- 
brates one  finds  many  protozoa  completely  covered 
with  cilia  ;  in  many  embryos  the  cilia  are  arranged 
in  definite  bands  round  the  body  ;  in  the  rotifers 
or  wheel  animalcules,  a  ring  of  cilia  round  the  Flo-  36._ciliated  cell  from 
mouth  gives  the  name  to  this  particular  group. 
The  gills  of  many  animals  are  covered  with 
cilia;  and  the  cells  of  portions  of  the  kidney  tubules  in  some 
animals  are  ciliated. 


the  intestine  of  a  mol- 
lusc.   (Engelmann.) 


CM.  III.]  CILIAKY   MOTION  25 

Ciliary  Motion. 

Ciliary  motion  reminds  one  of  amoeboid  movement,  but  it  is  much 
more  rapid,  and  more  orderly.  It  consists  of  a  rhythmical  movement 
of  the  cilia,  a  bending  over,  followed  by  a  lessening  of  the  curvature, 
repeated  with  great  frequency. 

When  living  ciliated  epithelium,  e.g.,  from  the  gill  of  a  mussel,  or 
from  the  mouth  of  the  frog,  is  examined  under  the  microscope  in  a 
drop  of  0'9  per  cent,  solution  of  common  salt  (normal  saline  solution), 
the  cilia  are  seen  to  be  in  constant  rapid  motion,  each  cilium  being 
fixed  at  one  end,  and  swinging  or  lashing  to  and  fro.  The  general 
impression  given  to  the  eye  of  the  observer  is  very  similar  to  that 
produced  by  waves  in  a  field  of  corn,  or  swiftly  running  and  rippling 
water,  and  the  result  of  their  movement  is  to  produce  a  continuous 
current  in  a  definite  direction,  and  this  direction  is  the  same  on  the 
same  surface,  being  usually  in  the  case  of  a  cavity  towards  the 
external  orifice. 

There  is  not  only  rhythmicality  in  the  movement  of  a  single 
cilium,  but  each  acts  in  harmony  with  its  fellows  in  the  same  cell, 
and  on  neighbouring  cells. 

The  uses  of  cilia  can  from  the  above  be  almost  guessed ;  in  the 
respiratory  passages  they  create  a  current  of  mucus  with  entangled 
dust  towards  the  throat ;  in  the  Fallopian  tube  or  oviduct  they  assist 
the  ovum  on  its  way  to  the  uterus ;  in  the  gullet  of  the  frog  they  act 
downwards  and  assist  swallowing ;  in  the  ciliated  protozoa  they  are 
locomotive  organs.  Over  the  gills  of  marine  animals  they  keep  up  a 
fresh  supply  of  water,  and  in  the  case  of  the  rotifers,  which  are  fixed 
animals,  the  current  of  water  brings  food  to  the  mouth. 

Ciliary  motion  is  independent  of  the  will,  and  of  the  influence 
of  the  nervous  system.  It  may  continue  for  many  hours  after 
death  or  removal  from  the  body,  provided  the  portion  of  tissue  under 
examination  be  kept  moist.  Its  independence  of  the  nervous  system 
is  shown  also  in  its  occurrence  in  the  lowest  invertebrate  animals, 
which  are  unprovided  with  anything  analogous  to  a  nervous  system. 
The  vapour  of  ether  or  chloroform  and  carbon  dioxide  arrest  the 
motion,  but  it  is  renewed  on  the  discontinuance  of  the  application. 
The  movement  ceases  when  the  cilia  are  deprived  of  oxygen,  although 
it  may  continue  for  a  time  in  the  absence  of  free  oxygen,  but  is 
revived  on  the  admission  of  this  gas.  The  contact  of  various  sub- 
stances, e.g.,  bile,  strong  acids,  and  alkalis,  will  stop  the  motion 
altogether ;  but  this  depends  on  destruction  of  the  delicate  substance 
of  which  the  cilia  are  composed.  Temperatures  above  45 D  C.  and  near 
0°  C.  stop  the  movement,  whereas  moderate  heat  and  dilute  alkalis 
are  favourable  to  the  action,  and  revive  the  movement  after  temporary 
cessation.  The  exact  explanation  of  ciliary  movement  is  not  known ; 


26 


EPITHELIUM 


[CH.  m. 


whatever  may  be  the  precise  cause,  the  movement  must  depend  upon 
some  changes  going  on  in  the  cell  to  which  the  cilia  are  attached,  as 
when  the  latter  are  cut  off  from  the  cell  the  movement  ceases,  and 
when  severed  so  that  a  portion  of  the  cilia  are  left  attached  to  the 
cell,  the  attached  and  not  the  severed  portions  continue  the  move- 
ment. It  has  been  suggested  by  Engelmann  that  the  contractile  part 
of  the  protoplasm  is  only  on  the  concave  side  of  a  curved  cilium,  and 
that  when  this  contracts  the  cilium  is  brought  downwards ;  when 
relaxation  occurs,  the  cilium  rebounds  by  the  elastic  recoil  of  the 
convex  border. 

Schafer  has  suggested  that  the  flow  of  hyaloplasm  backwards  and 
forwards  will  explain  ciliary  as  it  will  amoeboid  movement.  In  an 
amoeboid  cell,  the  spongioplasm  is  irregular  in  arrangement,  hence  an 
outflow  of  hyaloplasm  from  it  can  occur  in  any  direction.  But  in 
the  curved  projection  called  a  cilium,  the  hyaloplasm  can  obviously 
flow  in  only  one  direction  into  the  cilium  and  back  again.  The  flow 
of  hyaloplasm  into  the  cilium  will  raise  the  pressure  there  and  cause 
it  to  straighten  ;  a  movement  in  the  reverse  direction  will  cause  the 
cilium  to  curve. 

The  action  of  dilute  alkalis  and  acids  on  cilia  is  interesting. 
Dilute  acids  stop  ciliary  motion ;  and  cilia,  if  allowed  to  act  in  salt 
solution  for  a  time,  get  more  and  more  languid,  and  finally  cease 
acting;  in  popular  language  they  become  fatigued.  Now  we  shall 
find  in  muscle  that  fatigue  is  largely  due  to  the  accumulation  of  the 
acid  products  of  muscular  activity ;  remove  the  sarco-lactic  acid  and 
fatigue  passes  off.  It  is  probable  that  the  same  occurs  in  other 
contractile  tissues;  the  cilia  gradually  stop,  due  to  acid  products  of 
their  activity  collecting  around  them;  when  these  are  neutralised 
with  dilute  alkali  the  cilia  resume  activity. 

Nutrition  of  Epithelium. 

Epithelium  has  no  blood-vessels; 
it  is  nourished  by  lymph.  When  the 
blood  is  circulating  through  the  thin- 
walled  small  blood-vessels  in  the 
tissues  beneath  the  epithelium,  some 
of  its  fluid  constituents  escape.  This 
fluid  is  called  lymph ;  it  penetrates  to 
FIG.  37.-jagged  ceiis  from  the  middle  au  p^fa  Of  the  cellular  elements  of 

tissues  and  nourishes  them.  In  the 
thicker  varieties  of  epithelium,  the 
presence  of  the  irregular  minute  channels  between  the  cells  (fig.  37) 
enables  the  lymph  to  soak  more  readily  between  the  cells  than  it 
would  otherwise  be  able  to  do.  Epithelium  is  also  destitute  of 


vertical  section  of  the  gum  of  a  new- 

born  infant.    (Klein.) 


CH.  III.]  CHEMISTRY  OF   EPITHELIUM  27 

nerves  as  a  rule.  But  in  stratified  epithelium,  particularly  that 
covering  the  cornea  at  the  front  of  the  eye  and  in  the  deeper  layers 
of  the  epidermis,  a  plexus  of  nerve- fibrils  is  found. 

Chemistry  of  Epithelium. 

There  is  not  much  to  add  to  what  has  been  already  stated  con- 
cerning cells ;  protoplasm  and  nucleus  have  the  same  chemical  com- 
position as  has  been  already  mentioned  in  Chapter  II.  Two  new 
substances  have,  however,  been  mentioned  in  the  foregoing  chapter — 
namely,  mucin  and  keratin. 

Mucin. — This  is  a  widely  distributed  substance  occurring  in 
epithelial  cells  or  shed  out  by  them  (see  goblet  cells,  fig.  30).  It  also 
forms  the  chief  constituent  of  the  cementing  substance  between 
epithelial  cells.  We  shall  again  meet  with  it  in  the  intercellular 
substance  of  the  connective  tissues.  The  mucins  obtained  from 
different  sources  varies  somewhat  in  composition  and  reactions,  but 
they  all  agree  in  the  following  points : — 

(a)  Physical  character :  viscid  and  tenacious. 

(b)  Precipitability  from  solutions  by  acetic  acid.     They  all  dis- 

solve in  dilute  alkalis,  such  as  lime-water. 

(c)  They  are   all   compounds  of   protein,   with   a   carbohydrate 

material;  by  treatment  with  mineral  acid  this  is  hydro! ysed 
into  a  reducing  but  non-fermentable  sugar-like  substance. 
The  substance  mucin,  when  it  is  formed  within  cells  (goblet  cells, 
cells  of  mucous  glands),  is  preceded  in  the  cells  by  granules  of  a  sub- 
stance which  is  not  mucin,  but  is  readily  changed  into  mucin.     This 
precursor,  or  mother-substance  of  mucin,  is  called  mucigen  or  mucinogen. 
Keratin,  or  horny  material,  is  the  substance  found  in  the  surface 
layers  of  the  epidermis,  in  hairs,  nails,  hoofs,  and  horns.     It  is  very 
insoluble,  and   chiefly  differs  from  other  proteins  in  its  high  per- 
centage of  sulphur. 

The  silver  nitrate  reaction  of  cementing  substance.  The  principal 
chemical  reaction  which  is  employed  by  histologists  for  demonstrat- 
ing the  cement  or  intercellular  substance  which  binds  epithelial  cells 
together  was  formerly  supposed  to  be  due  to  the  formation  of  a 
silver-protein  compound  -which  was  reduced  by  sunlight.  Macallum 
has  conclusively  shown  that  this  is  not  the  case,  but  that  it  is  an 
inorganic  reaction.  Cementing  material  is  specially  rich  in  chlorides 
(mainly  sodium  chloride) ;  the  addition  of  silver  nitrate  leads  to  the 
formation  of  silver  chloride,  and  it  is  this  which  is  reduced  by  light. 
The  silver  reaction  obtained  in  other  tissues  is  similarly  explained : 
in  fact  silver  nitrate  is  a  micro-chemical  reagent  for  detecting  the 
localities  in  the  body  where  chlorides  occur.  According  to  Mac- 
allum the  nuclei  of  all  cells  are  entirely  free  from  chlorides. 


CHAPTER  IV 

THE-  CONNECTIVE   TISSUES 

THE  connective  tissues  are  the  following : — 

1.  Areolar  tissue.  6.  Jelly-like  tissue. 

2.  Fibrous  tissue.  7.  Cartilage. 

3.  Elastic  tissue.  8.  Bone  and  dentine. 

4.  Adipose  tissue.  9.  Blood. 

5.  Retiform  and  lymphoid  tissues. 

At  first  sight  these  numerous  tissues  appear  to  form  a  very 
heterogeneous  group,  including  the  most  solid  tissues  of  the  body 
(bone,  dentine)  and  the  most  fluid  (blood). 

But  on  examining  a  little  more  deeply,  one  finds  that  the  group- 
ing of  these  apparently  different  tissues  together  depends  on  a  number 
of  valid  reasons,  which  may  be  briefly  stated  as  follows : — 

1.  They  all  resemble  each  other  in  origin.     All  are  formed  from 

the  mesoblast,  the  middle  layer  of  the  embryo. 

2.  They  resemble  each  other  structurally;   that  is   to   say,  the 

cellular  element  is  at  a  minimum,  and  the  intercellular 
material  at  a  maximum. 

3.  They  resemble  each  other  functionally ;  they  form  the  skeleton, 

and  act  as  binding,  supporting,  or  connecting  tissues  to  the 
softer  and  more  vital  tissues. 

An  apology  is  sometimes  made  for  calling  the  blood  a  tissue, 
because  one's  preconceived  idea  of  a  tissue  or  texture  is  that  it  must 
be  something  of  a  solid  nature.  But  all  the  tissues  contain  water. 
Muscular  tissue  contains,  for  instance,  at  least  three-quarters^ of  its 
weight  as  water.  Blood,  after  all,  is  not  much  more  liquid  than 
muscle.  Blood,  moreover,  contains  cellular  elements  analogous  to  the 
cells  of  other  tissues,  but  separated  by  large  quantities  of  a  fluid 
intercellular  material  called  blood-plasma. 

Blood  is  also  mesoblastic,  and  thus  the  two  first  characteristics  of 
a  connective  tissue  are  present.  It  does  not  fulfil  the  third  condition 
by  contributing  to  the  support  of  the  body  as  part  of  the  skeleton, 
but  it  does  so  in  another  sense,  and  serves  to  support  the  body  by 
conveying  nutriment  to  all  parts. 


en. 


AREOLAR   TISSUE 


29 


Areolar  Tissue. 

This  is  a  very  typical  connective  tissue.  It  has  a  wide  distribu- 
tion, and  constitutes  the  subcutaneous,  subserous,  and  submucous 
tissues.  It  forms  sheaths  (fasciae)  for  muscles,  nerves,  blood-vessels, 
glands,  and  internal  organs,  binding  them  in  position  and  penetrat- 
ing into  their  interior,  supports  and  connects  their  individual  parts. 


Fio.  38. — Loose  areolar  tissue  from  the  subcutaneous  tissue  of  the  cat.  x  300.  Tliis  shows  the  two 
varieties  of  iibres,  and  two  of  the  varieties  of  connective-tissue"corpuscles,  namely,  the  lamellar 
cells  or  fibroblasts,  and  a  wander  cell.  1,  Lamellar  cell;  2,  wander  cell;  3,  elastic  fibres;  4, 
bundles  of  white  fibres.  (After  Szymonowicz.) 

On  microscopic  examination  it  is  soon  that  this  typical  connective 
tissue  consists  of  four  different  kinds  of  material,  or,  as  they  may  be 
termed,  histological  elements.  They  are : — 

(a)  Cells,  or  connective-tissue  corpuscles. 

(b)  A  homogeneous  matrix,  ground   substance,  or  intercellular 

material. 

(c)  White  fibres  )  r™  .,    ,  .    ,, 

(d)  Yellow  or  elastic  fibres  }  These  are  dePoslted  m  fche  matnx' 

In  considering  these  four  histological  elements  we  may  first  take 
the  fibres,  because  they  are  the  most  obvious  and  abundant  of  the 
structures  observable. 

The  white  fibres.  These  are  exquisitely  fine  fibres  collected  into 
bundles  which  have  a  wavy  outline.  The  bundles  run  in  different 
directions,  forming  an  irregular  network,  the  meshes  between  which 
are  called  areolce ;  hence  the  name  areolar. 

They  are  composed  of  the  chemical  substance  called  collagen.  On 
boiling  they  yield  gelatin;  some  chemists  regard  collagen  as  the 
anhydride  of  gelatin ;  but  whether  this  is  so  or  not,  the  gelatin  is 
undoubtedly  derived  from  the  collagen.  Gelatin  is  a  protein  though 


30 


THE   CONNECTIVE   TISSUES 


[CH.  IV. 


it  has  certain  characters  which  distinguish  it  from  most  members  of 
the  large  protein  family.  Its  most  characteristic  property  is  its 
power  of  jellying  or  gelatinising ;  that  is,  it  is  soluble  in  hot  water, 
and  on  cooling  the  solution  it  sets  into  a  jelly. 

The  yellow  or  elastic  fibres.     These  are  seen  readily  after  the  white 
fibres  are  rendered  almost  invisible  by  treatment  with  dilute  acetic 


FIG.  39.— 


,  39.— Horizontal  preparation  of  the  cornea  of 
frog,  stained  with  gold  chloride ;  showing  the 
network  of  branched  corneal  corpuscles.  The 
ground  substance  is  completely  colourless, 
x  400.  (Klein.) 


Fio.  40. — Ramified  pigment 
cells,  from  the  tissue  of 
the  choroid  coat  of  the 
eye.  x  350.  a,  Cell  with 
pigment ;  6,  colourless 
fusiform  cells.  (Kolli- 
ker.) 


acid,  or  after  staining  with  such  dyes  as  magenta  and  orcein,  for  which 
elastic  fibres  have  a  great  affinity.  They  are  bigger  than  the  white 
fibres,  have  a  distinct  outline,  and  a  straight  course ;  they  run  singly, 
branch,  and  join  neighbouring  fibres. 

The  material  of  which  the  elastic  fibres  are  composed  is  called 
elastin,  another  somewhat  exceptional  protein.  It  is  unaltered,  as 
we  have  seen,  by  dilute  acid.  It  also  resists  the  action  of  very 
strong  acid,  and  is  not  affected  by  boiling  water. 

Connective-tissue  corpuscles.  These  are  the  cells  of  connective 
tissue :  the  following  are  the  varieties  most  frequently  seen. 

1.  Lamellar  cells  (fig.  38).     These  are  branched,  and  the  branches 

of  neighbouring  cells  may  unite  as  in  the  cornea  (fig.  39) ; 
they  were  formerly  called  fibroblasts  from  the  mistaken 
idea  that  they  gave  rise  to  the  formation  of  fibres. 

2.  Pigment  cells.     These  are  lamellar  cells  laden  with  a  brown 

or  black  pigment.  They  are  seen  in  the  subcutaneous 
tissues  of  many  animals,  e.g.,  the  frog,  and  in  the  choroid 
coat  of  the  eyeball  (fig.  40). 

3.  Mast-cells.     These  are  usually  unbranched,  and  their  proto- 

plasm is  crowded  with  albuminous  granules  which  are 
stained  deeply  by  gentian-violet  and  other  basic  dyes. 


CH.  IV.] 


AEEOLAR   TISSUE 


31 


They  are  most  abundant  in  the  neighbourhood  of  blood- 
vessels (fig.  41).  The  name  was  given  to  them  by  Ehrlich, 
who  erroneously  believed  that  they  multiplied  on  a  rich 
diet.  Certain  cells  called  clasmatocytes  by  Eanvicr  are  very 
like  the  mast-cells,  but  their  protoplasm  branches. 


FIG.  41.— Subcutaneous  areolar  tissue  of  the  rat,  showing  a  small  blood-vessel,  with  numerous  mast- 
cells  in  the  neighbourhood,  also  two  fat-cells,  x  540.  1,  Small  blood-vessel ;  2,  mast-cell;  3, 
fat-cell.  (After  Szymonowicz.) 

4.   Wander  cells.    White  blood-corpuscles  which  have  emigrated 
from  the  neighbouriag  blood-vessels. 

The  ground-substance.     This   is   represented   in   fig.   38   by   the 
shaded  background. 

It  may  be  readily  demonstrated  in  a  silver  nitrate  preparation 
(fig.  42);  for  the  intercellular  material  has  the  same  property  of 
reducing  silver  salts  in  the  sun- 
light that  the  cement-material  of 
epithelium  has  (see  p.  27).  It 
becomes  in  consequence  dark 
brown,  with  the  exception  of  the 
spaces  occupied  by  the  corpuscles. 

The  spaces  intercommunicate 
like  the  cells,  and  being  consider- 
ably larger  than  the  cells  form  a 
ramifying  network  of  irregular 
channels,  which  were  first  termed 

by     V.     RecklinghaUSen     the      Soft      FIG.  42.— Ground-substance  of  connective  tissue, 
Tfri'nriTr'hff'n     r»r    lifflA    im'r>A    ^armla  stained  by  silver  nitrate.    The  cell  spaces  are 

j^anaLcnen,  or  nttie  juice  canals.         left  white.  (After  schafer.) 
Areolar   tissue  is  certainly  pro- 
vided with  blood-vessels,  but  the  tissue  elements  are,  as  in  all  tissues, 
provided  with  nutriment  by  the  exudation  from  the  blood  called 


32 


THE   CONNECTIVE   TISSUES 


[CII.  IV. 


lymph.     The  Soft  Kandlchen  enable  the  lymph  to  penetrate  to  every 
part  of  the  areolar  tissue. 

Fibrous  Tissue. 

This  is  a  kind  of  connective  tissue  in  which  the  white  fibres  pre- 
dominate ;  it  is  found  in  tendons  and  ligaments,  in  the  periosteum, 

dura  mater,  true  skin,  the  sclerotic 
coat  of  the  eye,  and  in  the  thicker 
fasciae  and  aponeuroses  of  muscle. 
The  tissue  is  one  of  great 
strength;  this  is  conferred  upon 
it  by  the  arrangement  of  the 
fibres,  the  bundles  of  which  run 
parallel,  union  here,  as  elsewhere, 
giving  strength.  The  cells  in 
tendons  (fig.  43)  are  forced  to 
take  up  a  similar  orderly  arrange- 
ment, and  are  arranged  in  long 
chains  in  the  ground-substance 
separating  the  bundles  of  fibres, 
and  are  more  or  less  regularly 
quadrilateral  with  large  round 
nuclei  containing  nucleoli,  which 
are  generally  placed  so  as  to  be 
nearly  contiguous  in  two  cells. 
The  cell  spaces  in  which  the  cells  lie  are  in  arrangement  like  the 
cells ;  they  can  be  brought  into  relief  by  staining  with  silver  nitrate 
(see  fig.  44). 


Fio.  43.— Caudal  tendon  of  young  rat,  showing  the 
arrangement,  form,  and  structure  of  the  tendon 
cells.  The  bundles  of  white  fibres  between 
which  they  lie  have  been  rendered  transparent 
and  indistinct  by  the  application  of  acetic 
acid,  x  300.  (Klein.) 


Fio.  44. — Cell  spaces  of  tendon,  brought  into  view  by  treatment  with  silver  nitrate. 
(After  Schafer.) 


Elastic  Tissue. 

This  is  a  form  of  connective  tissue  in  which  the  yellow  or  elastic 
fibres  predominate.  The  yellow  fibres  are  larger  than  those  found  in 
areolar  tissue  (see  fig.  45),  and  are  bound  into  bundles  by  areolar 


CH.  IV.] 


ADIPOSE   TISSUE 


33 


tissue.  It  is  found  in  the  ligamentum  nuchae  of  the  ox,  horse,  and 
many  other  animals ;  in  the  ligamenta  subflava  of  man ;  in  the 
arteries  and  veins,  constituting  the  fenestrated  coat  of  Henle ;  in  the 
lungs  and  trachea ;  in  the  stylo-hyoid,  thyro-hyoid,  and  cricothyroid 
ligaments ;  and  in  the  true  vocal  cords. 

Elastic  tissue,  being  extensible  and  elastic  (i.e.,  recoiling  after  it 
has  been  stretched),  has  a  most  important  use  in  assisting  muscular 


FIG.  46.— Transverse  section 
of  a  portion  of  lig.  nuchse, 
showing  the  angular  out- 
line of  the  fibres.  (After 
Stohr.) 

FIG.  45. — Elastic  fibres  from  the 
ligamenta  subflava.  x  200. 
(Sharpey.) 

tissue  in  a  mechanical  way,  and  so  lessening  the  wear  and  tear  of  such 
an  important  tissue  as  muscle.  Thus,  in  the  ligamenta  subflava  of  the 
human  vertebral  column  it  assists  in  the  maintenance  of  the  erect 
posture;  in  the  ligamentum  nuchae  in  the  neck  of  quadrupeds  it 
assists  in  the  raising  of  the  head  and  in  keeping  it  in  that  position. 
In  the  arterial  walls,  and  in  the  air  tubes  and  lungs,  it  has  a  similar 
important  action,  as  we  shall  see  when  discussing  the  subjects  of  the 
circulation  and  respiration. 


Adipose  Tissue. 

In  almost  all  regions  of  the  human  body  a  larger  or  smaller  quantity 
of  adipose  or  fatty  tissue  is  present;  the  chief  exceptions  are  the 
subcutaneous  tissue  of  the  eyelids,  penis  and  scrotum,  the  nymphse, 
and  the  cavity  of  the  cranium. 

Adipose  tissue  is  developed  in  connection  with  areolar  tissue,  and 
forms  in  its  meshes  little  masses  of  unequal  size  and  irregular  shape, 
to  which  the  term  lobules  is  applied. 


34  THE  CONNECTIVE  TISSUES  [CH.  IY. 

Under  the  microscope  each  lobule  is  found  to  consist  of  little 
vesicles  or  cells  which  present  dark,  sharply-defined  edges  when 
viewed  with  transmitted  light:  they  are  about  ^^  or  -^J-g-  of  an 
inch  in  diameter;  each  consists  of  a  structureless  and  colourless 
membrane  or  bag  formed  of  the  remains  of  the  original  protoplasm 
of  the  cell,  filled  with  fatty  matter,  which  is  liquid  during  life,  but 
is  in  part  solidified  (or  sometimes  crystallised)  after  death.  A 
nucleus  is  always  present  in  some  part  or  other  of  the  cell  proto- 
plasm, but  it  is  not  easily  visible  unless  the  tissue  is  stained. 

The  oily  matter  contained  in  the  cells  is  composed  of  the  com- 
pounds of  fatty  acids  with  glycerin,  which  are  named  olein,  stearin, 
and  palmitin.  On  the  addition  of  osmic  acid,  fat-cells  are  stained 
black;  this  is  due  to  the  olein  present,  which  reduces  the  osmium 
tetroxide  to  a  lower  oxide,  which  has  a  black  colour.  Fat  is 
stained  deep  yellow  by  Sudan  III.  and  red  by  Scharlach  R 

Fat-cells  are  developed  from  connective-tissue  corpuscles;  these 
colls  may  be  found  exhibiting  every  intermediate  gradation  between 

an  ordinary  corpuscle  and  a  mature  fat- 
cell.  The  process  of  development  is  as 
follows:  a  few  small  drops  of  oil  make 
their  appearance  in  the  protoplasm,  and 
by  their  confluence  a  larger  drop  is 
produced:  this  gradually  increases  in  size 
at  the  expense  of  the  original  protoplasm 
of  the  cell,  which  becomes  correspondingly 
diminished  in  quantity  till  in  the  mature 
cell  it  only  forms  a  thin  film,  with  a 
,FIO.  47.— Fat-ceiis  from  the  flattened  nucleus  imbedded  in  its  substance 

omentum  of  a  rat.    (Klein.)  /r>  .^  ,     .  L_. 

(figs.  41  and  47). 

A  large  number  of  blood-vessels  are  found  in  adipose  tissue,  which 
subdivide  until  each  lobule  of  fat  contains  a  fine  meshwork  of  capil- 
laries enshea thing  each  individual  fat-cell. 

Among  the  uses  of  adipose  tissue  these  are  the  chief : — 

a.  It   serves  as  a  store  of  combustible  matter  which  may  be 
reabsorbed  into  the  blood  when  occasion  requires,  and,  being  used 
up  in  the  metabolism  of  the  tissues,  helps  to  preserve  the  heat  of 
the  body. 

b.  The  fat  which  is  situated  beneath  the  skin  must,  by  its  want 
of  conducting  power,  assist  in  preventing  undue  waste  of  the  heat 
of  the  body  by  escape  from  the  surface. 

c.  As  a  packing  material,  fat  serves  very  admirably  to  fill  up 
spaces,  to  form  a  soft  and  yielding  yet  elastic  material  wherewith  to 
wrap  tender  and  delicate  structures,  or  form  a  bed  with  like  qualities 
on  which  such  structures  may  lie,  not  endangered  by  pressure.     As 
examples  of  situations  in  which  fat  serves  such  purposes  may  be 


CH-  IV.] 


RETIFORM   TISSUE 


35 


mentioned  the  palms  of  the  hands,  the  soles  of  the  feet,  and  the 
orbits. 

Retiform  Tissue. 

Ketiforni  or  reticular  tissue  is  a  kind  of  connective  tissue  in  which 
the  ground-substance  is  of  more  fluid  consistency  than  elsewhere. 


FIG.  48. — Retiform  tissue  from  a  lymphatic  gland,  from  a  section  which  has  been  treated  with  dilute 

potash.    (Schafer.) 

There  are  few  or  no  elastic  fibres  in  it,  and  the  white  fibres  run  in 
very  fine  bundles  forming  a  close  network.  The  bundles  are  covered 
and  concealed  by  flattened  con- 
nective-tissue corpuscles.  When 
these  are  dissolved  by  dilute  potash, 
the  fibres  are  plainly  seen  (fig.  48). 

The  statement  has  been  made  that  the 
fibres  of  retiform  tissue  are  chemically 
different  from  those  of  areolar  tissue,  in 
spite  of  the  fact  that  they  are  indistin- 
guishable microscopically,  and  in  many 
places  continuous  with  each  other.  Mrs 
Rosenheim  has  conclusively  proved  that 
chemical  differences  do  not  exist  between 
the  two  groups  of  fibres  ;  both  are  made 
of  collagen,  and  the  substance  termed 
reticulin  by  Siegfried  is  an  artifact ;  it  is 
merely  collagen  which  has  been  rendered 
resistant  and  insoluble  by  the  reagents 
(alcohol,  ether)  used  in  its  preparation. 


Adenoid  or  Lymphoid  Tissue. 

This  is  retiform  tissue  in  which 
the  meshes  of  the  network  are 
largely  occupied  by  lymph  cor- 
puscles. These  are  in  certain  foci 
actively  multiplying ;  they  get  into  the  lymph  stream,  which  washes 
them  into  the  blood,  where  they  become  the  variety  of  colourless 


FIG.  49.— Part  of  a  section  of  a  lymphatic  gland, 
from  which  the  corpuscles  have  been  for  the 
most  part  removed,  showing  the  supporting 
retiform  tissue.  (Klein  and  Noble  Smith.) 


36  THE  CONNECTIVE  TISSUES  [CH.  IV. 

corpuscles  called  lymphocytes.  It  is  found  in  the  lymphatic  glands, 
the  thymus,  the  tonsils,  in  the  follicular  glands  of  the  tongue,  in  Peyer's 
patches,  and  in  the  solitary  glands  of  the  intestines,  in  the  Malpighian 
corpuscles  of  the  spleen,  and  under  the  epithelium  of  many  mucous 
membranes. 

Jelly-like  Connective  Tissue. 

We  have  now  considered  connective  tissues  in  which  fibres  of  one 
or  the  other  kind  predominate,  and  some  in  which  the  cells  are  in 
preponderance.  We  come  lastly  to  a  form  of  connective  tissue  in 
which  the  ground -substance  is  in  excess  of  the  other  histological 
elements.  This  is  called  jelly-like  connective  tissue.  The  cells  and 
fibres  scattered  through  it  are  few  and  far  between.  It  is  found 
largely  in  the  embryo,  notably  in  the  Whartonian  jelly,  which  sur- 
rounds and  protects  the  blood-vessels  of  the  umbilical  cord.  In  the 
adult  it  is  found  in  the  vitreous  humour  of  the  eye. 

The  occurrence  of  large  quantities  of  ground-substance  in  such 
tissues  has  enabled  physiologists  to  examine  its  chemical  nature. 
Its  chief  constituents  are  water,  and  one  or  more  varieties  of  mucin- 
like  substances  termed  mucoids  and  mineral  salts  (especially  sodium 
chloride). 


CHAPTEE  V 

THE  CONNECTIVE   TISSUES   (continued) 

CARTILAGE,  BONE,  TEETH,  BLOOD 

Cartilage. 

CARTILAGE  is  popularly  termed  gristle.  It  may  be  divided  into  two 
chiof  kinds :  Hyaline  cartilage  ;  here  the  matrix  or  ground-substance 
is  clear  and  free  from  fibres :  Fibro-cartilage  ;  here  the  matrix  is  per- 


Fio.  50. — Section  of  articular  cartilage,    a,  Group  of  two  cells  ;  b,  group  of  four  cells  ;  d,  protoplasm  of 
cell  with  e,  fatty  granules ;  c,  nucleus.    (After  Schiifer.) 

vaded  with  connective-tissue  fibres;  when  these  are  of  the  white 
variety,  the  tissue  is  white  fibro-cartilage ;  when  they  are  of  the  yellow 
or  elastic  variety,  the  tissue  is  yellow  or  elastic  fibro-cartilage. 

87 


38 


THE   CONNECTIVE   TISSUES 


[CH.  V. 


Hyaline  Cartilage  is  found  in  the  following  places : — 

1.  Covering  the  articular  ends  of  bones ;  here  it  is  called  articular 
cartilage  (fig.  50). 

2.  Forming  the  rib-cartilages ;  here  it  is  called  costal  cartilage. 

3.  The  cartilages  of  the  nose,  of  the  windpipe,  of  the  external 
auditory  meatus,  and  the  greater  number  of  the  laryngeal  cartilages. 

4.  Temporary  cartilage:   rods  of   cartilage   which   prefigure    the 
majority  of  the  bones  in  process  of  development. 

Hyaline  cartilage  in  many  situations  (costal,  laryngeal,  tracheal) 
shows  a  tendency  to  become  calcified  late  in  life. 

On  boiling,  the  ground-substance  of  cartilage  yields  a  material 
called  chondrin.  This  resembles  gelatin  very  closely,  and  the  differ- 
ences in  its  reactions  are  due  to  the  fact  that  chondrin  is  not  a 
chemical  individual,  but  a  mixture  of  gelatin  with  varying  amounts 
of  mucoid  substances. 

White  Pibro-Cartilage  occurs — 

1.  As  inter-articular  fibro-cartilage — e.g.,  the  semilunar  cartilages 
of  the  knee-joint. 

2.  As  circumferential  or  marginal  cartilage,  as  on  the  edges  of  the 
acetabulum  and  glenoid  cavity. 

3.  As  connecting  cartilage — e.g.,  the  inter- vertebral  discs. 


SSI— .  Cells  of  car- 
tilage. 


....  Fibrous 
matrix. 


FIG.  51.— White  fibro-cartilage.    (Cadiat.) 


FIG.  52.— Yellow  or  elastic  fibro-cartilage. 
(Cadiat.) 


White  fibro-cartilage  (fig.  51)  is  composed  of  cells  and  a  matrix. 
The  latter  is  permeated  by  fibres  of  the  white  variety. 

In  this  kind  of  fibro-cartilage  it  is  not  unusual  to  find  portions  so 


Oil.  V.] 


CARTILAGE 


39 


densely  fibrous  that  no  cells  can  be  seen ;  but  in  other  parts  con- 
tinuous with  these,  cartilage-cells  are  freely  distributed. 

Yellow  or  Elastic  Pibro-Cartilage  is  found  in  the  pinna  of  the 
external  ear,  in  the  epiglottis  and  cornicula  laryngis,  and  in  the 
Eustachian  tube. 

The  cells  in  this  variety  of  cartilage  are  rounded  or  oval,  with 
well-marked  nuclei  and  nucleoli  (fig.  52).  The  matrix  in  which  they 
are  seated  is  pervaded  in  all  directions  by  fine  elastic  fibres,  which 
form  an  intricate  interlacement  about  the  cells :  a  small  and  variable 
quantity  of  non-fibrillated  hyaline  intercellular  substance  is  present 
around  the  cells. 

Development  of  Cartilage. — Like  other  connective  tissues,  car- 
tilage originates  from  mesoblast ;  the  cells  are  unbranched,  and  the 


••Illlllllillllllillllllllllll 


-c 


d 


Illlllllllllllllllilllllllllllllllllllllpp 

Fio.  53.— Plan  of  multiplication  of  cells  in  cartilage.  a,  Cell  in  its  capsule ;  b,  divided  into  two, 
each  with  a  capsule  ;  c,  primary  capsule  disappeared,  secondary  capsules  coherent  with  matrix  ; 
d,  tertiary  division  ;  e,  secondary  capsules  disappeared,  tertiary  coherent  with  matrix. 
(After  Sharpey.) 

disposition  of  the  cells  in  fully  formed  cartilage  in  groups  of  two, 
four,  etc.,  is  due  to  the  fact  that  each  group  has  originated  from  the 
division,  of  a  single  cell,  first  into  two,  each  of  these  again  into  two, 
and  so  on.  This  process  of  cell  division  is  accompanied  with  the 
usual  karyokinetic  changes. 

Each  cell  deposits  on  its  exterior  a  sheath  or  capsule ;  on  division 
each  of  the  daughter-cells  deposits  a  new  capsule  within  this,  and 
the  process  may  be  repeated  (see  fig.  53). 


40  THE    CONNECTIVE   TISSUES  [CH.  V. 

Thus  the  cells  get  more  and  more  separated.  The  fused  capsules 
form  a  very  large  part  of  the  matrix,  and  indications  of  their  previous 
existence  may  sometimes  be  seen  in  fully  formed  cartilage  by  the 
presence  of  faint  concentric  lines  around  the  cells. 

In  a  variety  of  cartilage  found  in  the  ears  of  rats  and  mice,  called 
cellular  cartilage,  the  cells  never  multiply  to  any  great  extent,  and 
they  are  only  separated  by  their  thickened  capsules. 

But  in  most  cartilages  the  cell-capsules  will  not  explain  the 
origin  of  the  whole  matrix,  for  intercellular  material  accumulates 
outside  the  capsules  and  still  further  separates  the  cells. 

By  certain  methods  of  double  staining,  this  twofold  manner 
of  formation  may  be  shown  very  markedly.  We  have  seen  that 
chondrin  obtained  by  boiling  cartilage  is  really  a  mixture  of  two 
substances ;  one  is  a  mucoid  material,  and  comes  from  the  capsules  ; 
the  other  is  gelatin,  which  comes  from  the  rest  of  the  ground - 
substance  which  is  collagenous.  In  hyaline  cartilage,  however,  the 
collagen  does  not  become  precipitated  to  form  fibres,  but  in  white 
fibro-cartilage  it  does.  In  yellow  fibro-cartilage  the  matrix  is  per- 
vaded by  a  deposit  of  elastin,  which  results  in  the  formation  of  a 
network  of  elastic  fibres. 

Bone. 

Bone  contains  nearly  50  per  cent,  of  water ;  the  solid  material  is 
composed  of  earthy  and  animal  matter  in  the  proportion  of  about  67 
per  cent,  of  the  former  to  33  per  cent,  of  the  latter.  The  earthy 
matter  is  composed  chiefly  of  calcium  phosphate,  but  besides  this, 
there  is  a  small  quantity  (about  11  of  the  67  per  cent.)  of  calcium 
carbonate,  calcium  fluoride,  and  magnesium  phosphate. 

The  animal  matter  is  chiefly  collagen,  which  is  converted  into 
gelatin  by  boiling. 

The  animal  and  earthy  constituents  of  bone  are  so  intimately 
blended  and  incorporated  the  one  with  the  other,  that  it  is  only  by 
severe  measures,  as  for  instance  by  a  white  heat  in  one  case  and  by 
the  action  of  concentrated  acids  in  the  other,  that  they  can  be 
separated.  Their  close  union,  too,  is  further  shown  by  the  fact  that 
when  by  acids  the  earthy  matter  is  dissolved  out,  or  on  the  other 
hand  when  the  animal  part  is  burnt  out,  the  shape  of  the  bone  is 
alike  preserved. 

The  proportion  between  these  two  constituents  of  bone  varies 
slightly  in  different  bones  in  the  same  individual  and  in  the  same 
bone  at  different  ages. 

To  the  naked  eye  there  appear  two  kinds  of  structure  in  different 
bones,  and  in  different  parts  of  the  same  bone,  namely,  the  dense  or 
compact,  and  the  spongy  or  cancellous  tissue.  Thus,  in  making  a 
longitudinal  section  of  a  long  bone,  as  the  humerus  or  femur,  the 


CH.  V.] 


BONE 


41 


articular  extremities  are  found  capped  on  their  surface  by  a  thin 
shell  of  compact  bone,  while  their  interior  is  made  up  of  the  spongy 
or  cancellous  tissue.  The  shaft,  on  the  other  hand,  is  formed  almost 
entirely  of  a  thick  layer  of  the  compact  bone,  and  this  surrounds  a 
central  canal,  the  medullary  cavity — so  called  from  its  containing  the 
medulla  or  marrow. 

In  the  flat  bones,  as  the  parietal  bone  or  the  scapula,  the  can- 
cellous structure  (diploe)  lies  between  two  layers  of  the  compact 
tissue,  and  in  the  short  and  irregular  bones,  as  those  of  the  carpus 
and  tarsus,  the  cancellous  tissue  fills  the  interior,  while  a  thin  shell 
of  compact  bone  forms  the  outside. 

Marrow. — There  are  two  distinct  varieties  of  marrow — the  red 
and  yellow. 

Red  marrow  is  the  connective  tissue  which  occupies  the  spaces  in 
the  cancellous  tissue ;  it  is  highly  vascular,  and  thus  maintains  the 


o 


Fir..  54. — Cells  of  the  red  marrow  of  the  guinea-pig,  highly  magnified,  o,  A  large  cell,  the  nucleus  of 
which  appears  to  be  partly  divided  into  three  by  constrictions  ;'  ?;,  a  cell,  the  nucleus  of  which 
shows  an  appearance  of  being  constricted  into  a  number  of  smaller  nuclei ;  c,  a  so-called  giant  cell 
or  myeloplaxe,  with  many  nuclei ;  d,  a  smaller  myeloplaxe,  with  three  nuclei ;  e — i,  proper  cells  of 
the  marrow.  (E.  A.  Schafer.) 

nutrition  of  the  spongy  bone,  the  interstices  of  which  it  fills.  It 
contains  a  few  fat-cells  and  a  large  number  of  marrow-cells.  The 
marrow-cells  are  amoeboid,  and  resemble  large  leucocytes;  the 
granules  of  some  of  these  cells  stain  readily  with  acid  and  neutral 
dyes,  but  a  considerable  number  have  coarse  granules  which  stain 
readily  with  basic  dyes  like  methylene  blue.  Among  the  cells  are 
some  smaller  nucleated  cells  of  the  same  tint  as  coloured  blood- 
corpuscles.  These  are  termed  erythrdblasts.  From  them  the  coloured 
corpuscles  of  the  blood  are  developed.  There  are  also  a  few  large 
cells  with  many  nuclei,  termed  giant  cells  or  myeloplaxes  (fig.  54). 

Yellow  marrow  fills  the  medullary  cavity  of  long  bones,  and  con- 
sists chiefly  of  fat-cells  with  numerous  blood-vessels;  many  of  its 
cells  also  are  the  colourless  marrow-cells  just  mentioned. 


42 


THE   CONNECTIVE  TISSUES 


[CH.  V. 


Periosteum  and  Nutrient  Blood-vessels. — The  surfaces  of 
bones,  except  the  part  covered  with  articular  cartilage,  are  clothed 
by  a  tough,  fibrous  membrane,  the  periosteum ;  and  it  is  from  the 
blood-vessels  which  are  distributed  in  this  membrane,  that  the  bones, 
especially  their  more  compact  tissue,  are  in  great  part  supplied  with 
nourishment ;  minute  branches  from  the  periostea!  vessels  enter  the 
little  foramina  on  the  surface  of  the  bone,  and  find  their  way  to  the 
Haversian  canals,  to  be  immediately  described.  The  long  bones  are 
supplied  also  by  a  proper  nutrient  artery  which,  entering  at  some 
part  of  the  shaft  so  as  to  reach  the  medullary  cavity,  breaks  up  into 
branches  for  the  supply  of  the  marrow,  from  which  again  small 
vessels  are  distributed  to  the  interior  of  the  bone.  Other  small 
blood-vessels  pierce  the  articular  extremities  for  the  supply  of  the 
cancellous  tissue. 

Microscopic  Structure  of  Bone. — Notwithstanding  the  differ- 
ences of  arrangement  just  mentioned,  the  structure  of  all  bone  is 
found  under  the  microscope  to  be  essentially  the  same. 


Fia.  55.— Transverse  section  of  compact  bony  tissue  (of  humerus).  Three  of  the  Haversian  canals  are 
seen,  with  their  concentric  rings ;  also  the  lacunae,  with  the  canaliculi  extending  from  them  across 
the  direction  of  the  lamellae.  The  Haversian  apertures  were  filled  with  air  and  debris  in  grinding 
down  the  section,  and  therefore  appear  black  in  the  figure,  which  represents  the  object  as  viewed 
with  transmitted  light.  The  Haversian  systems  are  so  closely  packed  in  this  section,  that  scarcely 
any  interstitial  lamellae  are  visible,  x  150.  (Sharpey.) 

Examined  with  a  rather  high  power  its  substance  is  found  to 
contain  a  multitude  of  small  irregular  spaces,  approximately  fusi- 
form in  shape,  called  lacunce,  with  very  minute  canals  or  canaliculi 
leading  from  them,  and  anastomosing  with  similar  little  prolonga- 
tions from  other  lacunae  (fig.  55).  In  very  thin  layers  of  bone,  no 


CH.  V.] 


BONE 


43 


other  canals  but  these  may  be  visible  ;  but  on  making  a  transverse 
section  of  the  compact  tissue  as  of  a  long  bone,  e.g.,  the  humerus  or 
ulna,  the  arrangement  shown  in  fig.  55  can  be  seen. 

The  bone  is  mapped  out  into  small  circular  districts,  at  or  about 
the  centre  of  each  of  which  is  a  hole,  around  which  is  an  appearance 
as  of  concentric  layers;  the  lacunce  and  canaliculi  follow  the  same 
concentric  plan  of  distribution  around  the  small  hole  in  the  centre, 
with  which  indeed  they  communicate. 

On  making  a  longitudinal  section,  the  central  holes  are  found  to 
be  simply  the  cut  extremities  of  small  canals  which  run  lengthwise 
through  the  bone,  anastomosing  with  each  other  by  lateral  branches 
(fig.  56);  these  canals  are  called  Haversian  canals,  after  the  name 


FIG.  56. — Longitudinal  section  from  the  human  ulna, 
showing  Haversian  canals,  lacunae,  and  canali- 
culi. (Rollett.) 


FIG.  57. — Bone-corpuscles  with  their  processes 
as  seen  in  a  thin  section  of  human  bone. 
(Eollett.) 


of  the  physician,  Clopton   Havers,  who   first  accurately  described 
them.     They  are  occupied  by  blood-vessels. 

The  lacunae  are  occupied  by  branched  cells,  which  are  called 
lone-cells,  or  lone- corpuscles  (fig.  57) ;  these  closely  resemble  ordinary 
branched  connective- tissue  corpuscles.  Bone  is  thus  essentially  con- 
nective tissue,  the  ground-substance  of  which  is  impregnated  with 
lime  salts.  The  bone-corpuscles  with  their  processes,  occupying  the 
lacunae  and  canaliculi,  correspond  exactly  to  the  connective- tissue 
corpuscles  lying  in  branched  spaces.  The  connection  of  the  lacunae  by 
the  canaliculi  allows  the  nutrient  lymph  to  pass  from  place  to  place, 


44 


THE   CONNECTIVE   TISSUES 


[CH.  Y. 


Lamellae  of  Compact  Bone. — In  the  shaft  of  a  long  bone  three 
distinct  sets  of  lamellae  can  be  clearly  recognised. 

1.  Circumferential  lamellae;    these    are    concentrically   arranged 
just  beneath  the  periosteum,  and  around  the  medullary  cavity. 

2.  Haver sian  lamellae ;  these  are  concentrically  arranged  around 
the  Haversian  canals  to  the  number  of  six  to  eighteen  around  each. 

3.  Interstitial  lamellae;  these  connect  the  systems  of  Haversian 
lamellae,  filling  the  spaces  between  them,  and  consequently  attaining 
their  greatest  development  where  the  Haversian  systems  are  few,  and 
vice  versd. 

The  ultimate  structure  of  the  lamellae  is  fibrous.     If  a  thin  film 
be  peeled  off  the  surface  of  a  bone,  from  which  the  earthy  matter  has 


FIG.  58.— Thin  layer  peeled 
off  from  a  softened  bone. 
This  figure,  which  is  in- 
tended to  represent  the 
reticular  structure  of  a 
lamella,  gives  a  better 
idea  of  the  object  when 
held  rather  farther  off 
than  usual  from  the  'eye. 
x  400.  (Sharpey.) 


FIG.  59. — Lamellae  torn  off  from  a  decalcified  human 
parietal  bone  at  some  depth  from  the  surface. 

a,  a,   Lamellae,   showing  intercrossing  fibres  ; 

b,  darker  part,  where  several  lamellae  are  super- 
posed ;  c,  perforating  fibres.  Apertures,  through 
which  perforating  fibres  had  passed,  are  seen 
especially  in  the  lower  part,  a,  a,  of  the  figure. 
(Allen  Thomson.) 


been  removed  by  acid,  and  examined  with  a  high  power  of  the  micro- 
scope, it  will  be  found  composed  of  very  slender  fibres  decussating 
obliquely,  but  coalescing  at  the  points  of  intersection,  as  if  here  the 
fibres  were  fused  rather  than  woven  together  (fig.  58).  These  are 
called  the  intercrossing  fibres  of  Sharpey  ;  they  correspond  to  the  white 
fibres  of  connective  tissue,  and  form  the  source  of  the  gelatin  obtained 
by  boiling  bone. 

In  many  cases,  as  in  the  parietal  bone,  the  lamellae  are  perforated 
by  tapering  fibres  called  the  perforating  fibres  of  Sharpey,  resembling 
in  character  the  ordinary  white  or  more  rarely  the  elastic  fibres, 


OH.  V.]  OSSIFICATION  45 

which  bolt  the  neighbouring  lamellae  together,  and  may  be  drawn  out 
when  the  latter  are  torn  asunder  (fig.  59).  These  perforating  fibres 
originate  from  ingrowing  processes  of  the  periosteum,  and  in  the  adult 
still  retain  their  connection  with  it. 

Development  of  Bone. — From  the  point  of  view  of  their  develop- 
ment, all  bones  may  be  subdivided  into  two  classes : — 

(a.)  Those  which  are  ossified  directly  or  from  the  first  in  a  fibrous 
membrane  afterwards  called  the  periosteum — e.g.,  the  bones  forming 
the  vault  of  the  skull,  parietal,  frontal,  and  a  certain  portion  of  the 
occipital  bones. 

(b.)  Those  whose  form,  previous  to  ossification,  is  laid  down  in 
hyaline  cartilage — e.g.,  humerus,  femur. 

The  process  of  development,  pure  and  simple,  may  be  best  studied 
in  bones  which  are  not  preceded  by  cartilage;  and  without  a  know- 
ledge of  this  process  (ossification  in  membrane),  it  is  impossible  to 
understand  the  more  complex  series  of  changes  through  which  such 
a  structure  as  the  cartilaginous  femur  of  the  f oetus  passes  in '  its 
transformation  into  the  bony  femur  of  the  adult  (ossification  in 
cartilage). 

Ossification  in  Membrane. — The  membrane,  afterwards  forming 
the  periosteum,  from  which  such  a  bone  as  the  parietal  is  developed, 
consists  of  two  layers — an  external  fibrous,  and  an  internal  cellular  or 
osteogenetic. 

The  external  layer  is  made  up  of  ordinary  fibrous  tissue.  The 
internal  layer  consists  of  a  network  of  fine  fibrils  with  a  large  number 
of  nucleated  cells  (osteoblasts),  some  of  which  are  oval,  others  drawn 
out  into  long  branched  processes:  it  is  more  richly  supplied  with 
capillaries  than  the  outer  layer.  It  is  this  portion  of  the  periosteum 
which  is  immediately  concerned  in  the  formation  of  bone. 

In  such  a  bone  as  the  parietal,  ossification  is  preceded  by  an  in- 
crease in  the  vascularity  of  this  membrane,  and  then  spicules,  starting 
from  a  centre  of  ossification  near  the  centre  of  the  future  bone,  shoot 
out  in  all  directions  towards  the  periphery.  These  primary  bone 
spicules  consist  of  fibres  which  are  termed  osteogenetic  fibres;  they 
are  composed  of  a  soft,  transparent  substance  called  osteogen,  around 
and  between  which  calcareous  granules  are  deposited.  The  fibres  in 
their  precalcified  state  are  likened  to  bundles  of  white  fibrous  tissue, 
to  which  they  are  similar  in  chemical  composition,  but  from  which 
they  differ  in  being  stiffer  and  less  wavy.  The  deposited  granules 
after  a  time  become  so  numerous  as  to  imprison  the  fibres,  and  bony 
spiculae  result.  By  the  junction  of  the  osteogenetic  fibres  and  their 
resulting  bony  spicules  a  meshwork  of  bone  is  formed.  The  osteo- 
genetic fibres,  which  become  indistinct  as  calcification  proceeds,  persist 
in  the  lamellae  of  adult  bone  as  the  intercrossing  fibres  of  Sharpey. 
The  osteoblasts,  being  in  part  retained  within  the  bony  layers  thus 


46  THE  CONNECTIVE  TISSUES  [CH.  v- 

produced,  form  bone  corpuscles.  On  the  bony  trabeculse  first  formed, 
layers  of  osteoblastic  cells  from  the  osteogenetic  layer  of  the  perios- 
teum repeat  the  process  just  described ;  and  as  this  occurs  in  several 
thicknesses,  and  also  at  the  edges  of  the  spicules  previously  formed, 
the  bone  increases,  both  in  thickness,  length  and  breadth.  The  pro- 
cess is  not  completed  by  the  time  the  child  is  born ;  hence  the  fonta- 
nelles  or  still  soft  places  on  the  heads  of  infants.  Fig.  60  represents 
a  small  piece  of  the  growing  edge  of  a  parietal  bone. 


FIG.  60.— Part  of  the  growing  edge  of  the  developing  parietal  bone  of  a  foetal  cat.  sp,  Bony  spicules  with 
some  of  the  osteoblasts  imbedded  in  them,  producing  the  lacuna1 ;  of,  osteogenetic  fibres  prolonging 
the  spicules  with  osteoblasts  (ostj  between  them  and  applied  to  them.  (Schafer.) 

The  bulk  of  the  primitive  spongy  bone  is  in  time  converted  into 
compact  bony  tissue,  with  Haversian  systems.  Those  portions  in  the 
interior  not  converted  into  bone  become  filled  with  the  red  marrow 
of  the  cancellous  tissue. 

Ossification  in  Cartilage. — Under  this  heading,  taking  the  femur 
or  any  other  long  bone  as  an  example,  we  have  to  consider  the  process 
by  which  the  solid  cartilaginous  rod  which  represents  the  bone  in  the 
foetus  is  converted  into  the  hollow  cylinder  of  compact  bone  with 
expanded  ends  formed  of  cancellous  tissue  of  which  the  adult  bone  is 
made  up.  We  must  bear  in  mind  the  fact  that  this  foetal  cartila- 
ginous femur  is  many  times  smaller  than  even  the  medullary  cavity 
of  the  shaft  of  the  mature  bone,  and,  therefore,  that  not  a  trace  of  the,- 


cm.  v.] 


OSSIFICATION 


47 


l.m 


original  cartilage  can  be  present  in  the  femur  of  the  adult.  Its  pur- 
pose is  indeed  purely  temporary;  and,  after  its  calcification,  it  is 
gradually  and  entirely  absorbed. 

The  cartilaginous  rod  which 
forms  the  precursor  of  a  festal 
long  bone  is  sheathed  in  a  mem- 
brane termed  the  perichondrium, 
which  exactly  resembles  the  peri- 
osteum just  described. 

Between  the  cartilaginous  pre- 
figurement  of  which  the  foetal 
long  bone  consists  and  the  adult 
bone  there  are  several  inter- 
mediate stages. 

The  process  may,  however,  be 
most  conveniently  described  as 
occurring  in  three  principal 
stages. 

The  first  stage  consists  of  two 
sets  of  changes,  one  in  the  carti- 
lage, the  other  under  the  peri- 
chondrium. These  take  place 
side  by  side.  In  the  cartilage 
the  cells  in  the  middle  *  become 
enlarged  and  separated  from  one 
another.  The  cartilage-cells  on 
each  side  get  arranged  in  rows  in 
the  direction  of  the  extremities 
of  the  cartilaginous  rod.  If  at 
this  stage  one  cuts  the  little  em- 
bryonic bone  with  a  knife,  the 
knife  encounters  resistance,  and 
there  is  a  sensation  of  grittiness. 
This  is  due  to  the  fact  that  cal- 
careous particles  are  deposited  in 
the  matrix;  and  in  consequence 
of  this  the  matrix  stains  differ- 
ently with  histological  reagents 
from  the  unaltered  matrix. 
Simultaneously  with  this,  the 
periosteal  tissue  is  forming  layer 


//u 


*  This  is  the  case  in  nearly  all  the 
long  bones,  but  in  the  terminal  pha- 
langes the  change  occurs  first,  not  in 
the  middle  but  at  their  distal  extremities. 


FIG.  61.— Section  of  two  foetal  phalanges;  the  carti- 
lage-celis  in  the  centre  of  B  are  enlarged  and 
separated  from  one  another  by  calcified  matrix. 
im,  Layer  of  bone  deposited  under  the  perios- 
teum ;  o,  layer  of  osteoblasts  by  which  this 
layer  was  formed.  The  rows  of  cartilage-cells 
are  seen  on  each  side  of  the  centre  of  calcifica- 
tion. In  A,  the  terminal  phalanx,  the  changes 
begin  at  the  tip.  (After  Dixey.) 


48 


THE   CONNECTIVE   TISSUES 


[CH.  V. 


after  layer  of  true  bone;  this  is  formed  exactly  in  the  same  way 
as  in  such  a  bone  as  the  parietal ;  by  the  agency  of  the  osteoblasts, 
osteogenetic  fibres,  and  then  spicules  of  bone,  are  formed  by  deposit 
of  calcareous  matter.  As  the  layers  are  formed,  some  of  the  osteo- 
blasts get  walled  in  between  the  layers  and  become  bone-cells. 

In  the  later  part  of  this  stage  the  calcareous  deposit  between  the 
cartilage-cells  cuts  them  off  from  nutrition,  and  they  in  consequence 
waste,  leaving  spaces  that  are  called  the  primary  areolce.  The 
calcareous  deposit  creeps  up  between  the  rows  of  cartilage-cells, 


ir. 


FIG.  (>2. — Ossification  in  cartilage  showing  stage  of  irruption.  The  shrunken  cartilage-cells  are  seen 
in  the  primary  areolae.  At  ir  an  irruption  of  the  subperiosteal  tissue  has  penetrated  the  sub- 
periosteal  bony  crust.  (After  Lawrence.) 

enclosing  them  in  calcified  boxes  containing  one,  two,  or  more  cells 
each.  The  wasting  of  the  cells  leads  here  also  to  the  formation  of 
primary  areolae. 

We  may  roughly  compare  the  two  sets  of  cells  engaged  in  the 
process  to  two  races  of  settlers  in  a  new  country.  The  cartilage-cells 
constitute  one  race,  and  so  successfully  build  for  themselves  calcareous 
homes  as  to  be  completely  boxed  up ;  so  they  waste  and  disappear, 
leaving  only  the  walls  of  their  homes  enclosing  the  spaces  called 
primary  areolse.  The  osteoblasts,  the  other  race  of  cells  under  the 


CH.  V.] 


OSSIFICATION 


49 


^^~5 


perichondrium,  are  forming  layers  of  true  bone  in  that  situation. 
Some,  it  is  true,  get  walled  in  in  the  process,  and  become  bone- 
corpuscles,  but  the  system  of  intercommunicating  lacunae  and 
canaliculi  maintains  their  nutrition. 

These  two  races  are  working  side  by  side,  and  at  first  do  not 
interfere  with  each  other.  But  soon  comes  a  declaration  of  war,  and 
we  enter  upon  the  second  stage  of  ossification,  which  is  very  appro- 
priately called  the  stage  of  irruption  (fig.  62).  Breaches  occur  in  the 
bony  wall  which  the  osteoblasts  have 

built  like  a  girdle  round  the  calcifying  ^  =•  fjf^g&jj^ 
cartilage,  and  through  these  the  peri- 
chondrial  tissue  pours  an  invading  army 
into  the  calcified  cartilage.  This  con- 
sists of  osteoblasts,  the  bone  -  formers ; 
osteoclasts,  or  the  bone  -  destroyers ;  the 
latter  are  large  cells,  similar  to  the  mye- 
loplaxes  found  in  marrow  (fig.  54).  There 
are  also  a  few  fibres,  and  a  store  of 
nutrient  supply  in  the  shape  of  blood- 
vessels. 

Having  got  inside,  the  osteoclasts  set 
to  work  to  demolish  the  homes  of  the 
cartilage-cells,  the  walls  of  the  primary 
areolse,  and  thus  large  spaces  are  formed, 
which  are  called  the  secondary  areolce,  or 
the  medullary  spaces.  On  the  ruins  of 
the  calcified  cartilage,  the  osteoblasts  pro- 
ceed to  deposit  true  bone  in  layers,  just 
as  they  were  wont  to  do  in  their  own 
country,  under  the  periosteum. 

The  third  stage  of  ossification  is  a 
repetition  of  these  two  stages  towards  the 
extremities  of  the  cartilage.  The  carti- 
lage-cells get  flattened  and  arranged  in 
rows;  calcareous  deposit  occurs  around 
these,  and  primary  areolae  result;  then 
follows  the  advance  of  the  subperiosteal 
tissue,  the  demolition  of  the  primary 
secondary  areolae,  and  the  deposit  of  true  bone.  At  the  same  time, 
layer  upon  layer  is  still  being  deposited  beneath  the  periosteum, 
and  these,  from  being  at  first  a  mere  girdle  round  the  waist  of  the 
bone,  now  extend  towards  its  extremities. 

The  next  figure  (fig.  63)  is  a  magnified  view  of  the  line  of  advance. 

The  bone  which  is  first  formed  is  less  regularly  lamellar  than  that 
of  the  adult.  The  lamellae  are  not  deposited  till  after  birth  and 

D 


gi 

fying  cartilage.  Calcified  tra beculse 
are  seen  extending  between  the 
columns  of  cartilage-cells,  c,  Car- 
tilage-cells ;  a,  b,  secondary  areolse. 
x  140.  (Sharpey.) 


areolae,   the    formation   of 


50  THE  CONNECTIVE  TISSUES  [CH.  V. 

their  formation  is  preceded  by  a  considerable  amount  of  absorption. 
To  carry  our  simile  further,  the  osteoblasts  are  not  satisfied  with  the 
rough  constructions  that  they  were  first  able  to  make,  but  having 
exterminated  the  cartilage,  they  destroy  (again  through  the  agency 
of  the  regiment  of  giant  osteoclasts)  their  first  work,  and  build  regular 
lamellae,  leaving  lacunae  for  the  accommodation  of  those  who  desire  to 
retire  from  active  warfare. 

About  this  time,  too,  the  marrow  cavity  is  formed  by  the  absorp- 
tion of  the  bony  tissue  that  originally  occupied  the  centre  of  the 
shaft.  Here  the  osteoclasts  have  again  to  do  the  work,  and,  with  this 
final  act  of  destruction,  all  remains  of  any  calcified  cartilage  of  the 
foetal  bone  entirely  disappear. 

The  formation  of  a  so-called  cartilage  bone  is  thus,  after  all,  a 
formation  of  bone  by  subperiosteal  tissue,  just  as  it  is  in  the  so-called 
membrane  bone. 

After  a  time  the  cartilage  at  the  ends  of  the  shaft  begins  to  ossify 
independently,  and  the  epiphyses  are  formed.  They  are  not  joined 
on  to  the  shaft  till  late  in  life,  so  that  growth  of  the  bone  in  length 
can  continue  till  union  takes  place. 

Bone  grows  in  width  by  the  deposition  of  layers  under  the  perios- 
teum, like  successive  rings  formed  under  the  bark  of  a  growing  tree. 
This  was  shown  long  before  the  histological  details  which  we  have 
described  were  made  out  by  Sharpey.  Silver  rings  were  placed  by 
Duhamel  around  the  bones  of  young  pigeons.  When  killed  later,  the 
rings  were  completely  covered  in  by  bone ;  and  in  the  animals  killed 
last,  were  even  found  in  the  central  cavity.  Another  series  of  experi- 
ments was  performed  upon  pigs.  The  young  animals  were  fed 
alternately  on  ordinary  food  and  food  dyed  by  the  red  pigment 
madder.  The  new  bony  tissue  acts  like  what  dyers  called  a 
"  mordant " :  it  fixes  the  dye,  and  the  rings  of  bone  deposited  during 
the  madder  periods  were  distinctly  red  in  colour. 

The  importance  of  the  periosteum  in  bone  formation  has  always 
been  recognised  by  surgeons.  When  removing  a  piece  of  bone  they 
are  careful,  if  possible,  to  leave  the  periosteum  behind :  this  leads  to 
regeneration  of  the  lost  bone.  If  it  is  absolutely  necessary  to  remove 
the  periosteum,  successful  cases  have  occurred  in  which  the  living 
periosteum  from  an  animal  has  effectively  been  transplanted. 
MacEwen  has  recently  shown  that  minute  fragments  of  living  bone 
are  even  more  efficacious  in  virtue  of  the  bone-cells  they  contain. 

The  Teeth. 

During  the  course  of  his  life,  man,  in  common  with  most  other 
mammals,  is  provided  with  two  sets  of  teeth ;  the  first  set,  called  the 
temporary  or  milk  teeth,  makes  its  appearance  in  infancy,  and  is  in 


CH.  V.] 


THE   TEETH 


51 


the  course  of  a  few  years  shed  and  replaced  by  the  second  or  per- 
manent set. 

The  temporary  or  milk  teeth  are  ten  in  number  in  each  jaw, 
namely,  on  either  side  from  the  middle  line  two  incisors,  one  canine, 
and  two  deciduous  molars,  and  are  replaced  by  ten  permanent  teeth. 
The  number  of  permanent  teeth  in  each  jaw  is,  however,  increased  to 
sixteen  by  the  development  of  three  molars  on  each  side  of  the  jaw, 
which  are  called  the  permanent  or  true  molars. 

The  following  tables  show  the  average  times  of  eruption  of  the 
Temporary  and  Permanent  teeth.  In  both  cases  the  eruption  of  any 
given  tooth  of  the  lower  precedes,  as  a  rule,  that  of  the  corresponding 
tooth  of  the  upper  jaw. 

Temporary  or  Milk  Teeth. 
The  figures  indicate  in  months  the  age  at  which  each  tooth  appears. 


INCISORS. 

DECIDUOUS 
FIRST 
MOLARS. 

CANINES. 

DECIDUOUS 
SECOND 
MOLARS. 

6 

12 

18 

24 

Permanent  Teeth. 

The  age  at  which  each  tooth  is  cut  is  indicated  in  this  table  in  years. 


FIRST 
MOLARS. 

INCIS 
CENTRALS. 

ORS. 
LATERALS. 

BICUSPID 
MOL 

FIRST. 

3  OR  PRE- 
ARS. 

SECOND. 

CANINES. 

SECOND 
MOLARS. 

THIRD 
MOLARS  OR 
WISDOMS. 

6 

7 

8 

9 

10 

11 

12 

17  to  25 

The  times  of  eruption  given  in  the  above  tables  are  only  approxi- 
mate: the  limits  of  normal  variation  are  tolerably  wide.  Certain 
diseases  affecting  the  bony  skeleton,  e.g.  Kickets,  retard  the  eruptive 
period  considerably. 

It  is  important  to  notice  that  it  is  a  molar  which  is  the  first  tooth 
to  be  cut  in  the  permanent  dentition,  not  an  incisor  as  in  the  case  of 
the  temporary  set,  and  also  that  it  appears  behind  the  last  deciduous 
molar  on  each  side. 

The  third  molars,  often  called  Wisdoms,  are  sometimes  unerupted 
through  life  from  want  of  sufficient  jaw  space  and  the  presence  of 
the  other  teeth ;  cases  of  whole  families  in  which  their  absence  is  a 
characteristic  feature  are  occasionally  met  with. 


52  THE   CONNECTIVE   TISSUES  [CH.  V. 

When  the  teeth  are  fully  erupted  it  will  be  observed  that  the  upper 
incisors  and  canines  project  obliquely  over  the  lower  front  teeth,  and 
the  external  cusps  of  the  upper  bicuspids  and  molars  lie  outside  those 
of  the  corresponding  teeth  in  the  lower  jaw.  This  arrangement 
allows  to  some  extent  of  a  scissor-like  action  in  dividing  and  biting 
food  in  the  case  of  incisors ;  and  a  grinding  motion  in  that  of  the 
bicuspids  and  molars  when  the  side  to  side  movements  of  the  lower 
jaw  bring  the  external  cusps  of  the  lower  teeth  into  direct  articula- 
tion with  those  of  the  upper,  and  then  cause  them  to  glide  down  the 
inclined  surfaces  of  the  external  and  up  the  internal  cusps  of  these 
same  upper  teeth  during  the  act  of  mastication. 

The  work  of  the  canine  teeth  in  man  is  similar  to  that  of  his 
incisors.  Besides  being  a  firmly  implanted  tooth  and  one  of  stronger 
substance  than  the  others,  the  canine  tooth  is  important  in  preserving 
the  shape  of  the  angle  of  the  mouth,  and  by  its  shape,  whether 
pointed  or  blunt,  long  or  short,  it  becomes  a  character  tooth  of  the 
dentition  as  a  whole  in  both  males  and  females. 

Another  feature  in  the  fully  developed  and  properly  articulated 
set  of  teeth  is  that  no  two  teeth  oppose  each  other  only,  but  each 
tooth  is  in  opposition  with  two,  except  the  upper  Wisdom,  usually  a 
small  tooth.  This  is  the  result  of  the  greater  width  of  the  upper 
incisors,  which  so  arranges  the  "  bite "  of  the  other  teeth  that  the 
lower  canine  closes  in  front  of  the  upper  one. 

Should  a  tooth  be  lost,  therefore,  it  does  not  follow  that  its  former 
opponent  remaining  in  the  mouth  is  rendered  useless  and  thereby 
liable  to  be  removed  from  the  jaw  by  a  gradual  process  of  extrusion 
commonly  seen  in  teeth  that  have  no  work  to  perform  by  reason  of 
absence  of  antagonists. 

Structure  of  a  Tooth. 

A  tooth  is  generally  described  as  possessing  a  crown,  neck,  and  root. 

The  crown  is  the  portion  which  projects  beyond  the  level  of  the 
gum.  The  neck  is  that  constricted  portion  just  below  the  crown 
which  is  embraced  by  the  free  edges  of  the  gum ;  and  the  root  includes 
all  below  this. 

On  making  longitudinal  and  transverse  sections  through  its  centre 
(figs.  64,  65),  a  tooth  is  found  to  be  composed  of  a  hard  material, 
dentine  or  ivory,  which  is  moulded  around  a  central  cavity  which 
resembles  in  general  shape  the  outline  of  the  tooth  ;  the  cavity  is 
called  the  pulp  cavity  from  its  containing  the  very  vascular  and 
sensitive  pulp. 

The  tooth-pulp  is  composed  of  loose  connective  tissue,  blood-vessels, 
nerves,  and  large  numbers  of  cells  of  varying  shapes ;  on  the  sur- 
face in  close  connection  with  the  dentine  is  a  specialised  layer  of 


CH.  V.] 


STRUCTURE   OF   A   TOOTH 


53 


cells  called  odontoblasts,  which  are  elongated  columnar  cells  with  a 
large  nucleus  at  the  tapering  ends  farthest  from  the  dentine. 


FIG.  64. — A,  longitudinal  section  of  a  human  molar  tooth ;  c,  cement ;  d,  dentine ;  e,  enamel ;  v,  pulp- 
cavity.    (Owen.) 
B,  transverse  section.    The  letters  indicate  the  same  as  in  A. 

The  blood-vessels  and  nerves  enter  the  pulp  through  a  small 
opening  at  the  apical  extremity  of  each  root.     The  nerves  terminate 


Enamel 


Dentine. 


Cement 


Lower  jaw-bone 


Cement. 


FIG.  65.— Premolar  tooth  of  cat  in  situ. 


54  THE   CONNECTIVE   TISSUES  [CH.  V. 

by  branching  into  fine  fibrillre  which  enter  the  dentinal  tubes.  No 
lymphatics  have  been  seen  in  the  pulp. 

A  layer  of  very  hard  calcareous  matter,  the  enamel,  caps  that  part 
of  the  dentine  which  projects  beyond  the  level  of  the  gum ;  while 
sheathing  the  portion  of  dentine  which  is  beneath  the  level  of  the 
gum,  is  a  layer  of  true  bone,  called  the  cement  or  crusta  petrosa. 

At  the  neck  of  the  tooth,  where  the  enamel  and  cement  come  into 
contact,  each  is  reduced  to  an  exceedingly  thin  layer ;  here  the  cement 
overlaps  the  enamel,  and  is  prolonged  over  it.  On  the  surface  of  the 
crown  of  the  tooth,  when  it  first  comes  through  the  jaw,  is  a  thin 
membrane  called  Nasmyth's  membrane,  or  the  cuticle  of  the  tooth. 
The  covering  of  enamel  becomes  thicker  towards  the  crown,  and  the 
cement  towards  the  lower  end  or  apex  of  the  root. 

Dentine  or  Ivory. 

Dentine  closely  resembles  bone  in  chemical  composition.  It  con- 
tains, however,  only  10  per  cent,  of  water.  The  proportion  in  a 
hundred  parts  of  the  solids  is  about  twenty-eight  animal  to  seventy- 
two  of  earthy  matter.  The  former,  like  the  animal  matter  of  bone, 


9  c 

FIG.  66.— Section  of  a  portion  of  the  dentine  and  cement  from  the  middle  of  the  root  of  an  incisor  tooth, 
a,  Dentinal  tubules  ramifying  and  terminating,  some  of  them  in  the  interglobular  spaces  5  and  c ;  d, 
inner  layer  of  the  cement  with  numerous  closely  set  canaliculi ;  e,  outer  layer  of  cement ;  /,  lacunrc ; 
g,  canaliculi.  x  350.  (Kolliker.) 

may  be  converted  into  gelatin  by  boiling.  It  also  contains  a  trace  of 
fat.  The  earthy  matter  is  made  up  chiefly  of  calcium  phosphate,  with 
a  small  portion  of  the  carbonate,  and  traces  of  calcium  fluoride  and 
magnesium  phosphate. 

Under  the  microscope  dentine  is  seen  to  be  finely  channelled 
by  a  multitude  of  delicate  tubes,  which  by  their  inner  ends  com- 
municate with  the  pulp -cavity,  and  by  their  outer  extremities  come 
into  contact  with  the  under  part  of  the  enamel  and  cement,  and 
sometimes  even  penetrate  them  for  a  greater  or  less  distance  (figs.  66, 
68).  The  matrix  in  which  these  tubes  lie  is  composed  of  "  a  reticulum 
of  fine  fibres  of  connective  tissue  modified  by  calcification,  and  where 


CH.  V.] 


ENAMEL 


55 


that  process  is  complete,  entirely  hidden  by  the  densely  deposited  lime 
salts  "  (Mummery). 

The  tubules  of  the  dentine,  the  average  diameter  of  which  at  their 
inner  and  larger  extremity  is  ^Yo  of  an  inch,  contain  fine  pro- 
longations from  the  tooth-pulp  which  are  processes  of  the  odonto- 
blasts,  the  columnar  cells  lining  the  pulp-cavity  together  with  nerve- 
fibrils;  the  relation  of  these  processes  to  the  tubules  in  which  they 
lie  is  precisely  similar  to  that  of  the  processes  of  the  bone-corpuscles 
to  the  canaliculi  of  bone.  The  outer  portion  of  the  dentine,  under- 
lying the  cement,  and  the  enamel  to  a  much  lesser  degree,  forms  a 
more  or  less  distinct  layer  termed  the  granular  or  interglobular  layer 
(fig.  66).  It  is  characterised  by  the  presence  of  a  number  of  irregular 
minute  cavities.  The  explanation  of  these  will  be  seen  when  we 
study  the  development  of  a  tooth. 

Enamel. 

Enamel  is  by  far  the  hardest  tissue  in  the  body ;  it  is  composed  of 
the  same  inorganic  compounds  that  enter  into  the  composition  of 
dentine  and  bone.  According  to  Tomes,  it  contains  no  animal  matter 
at  all,  and  only  2  or  3  per  cent,  of  water.  Gelatin  is  a  characteristic 


FIG.  67. — Enamel  prisms.  A,  fragments  and  single  prisms  of  the  transversely-striated  enamel,  isolated 
by  the  action  of  hydrochloric  acid.  B,  surface  of  a  small  fragment  of  enamel,  showing  the  hexa- 
gonal ends  of  the  fibres  with  darker  centres,  x  350.  (Kcilliker.) 

product  of  connective  tissue,  and  enamel  is  not  a  connective  tissue, 
but  is  epithelial  in  origin. 

Examined  under  the  microscope,  enamel  is  found  composed  of  six- 
sided  prisms  (figs.  67,  68)  5^()()  of  an  inch  in  diameter,  which  are  set 
on  end  on  the  surface  of  the  dentine,  and  fit  into  corresponding 
depressions  in  the  same, 


56 


THE   CONNECTIVE  TISSUES 


[CH.   V. 


Crusta  Petrosa. 

The  crusta  petrosa  or  cement  (fig.  66,  e,d)  is  composed  of  true  bone, 
and  in  it  are  lacunse  (/)  and  canaliculi  (g),  which  sometimes  com- 
municate with  the  outer  finely  branched  ends 
of  the  dentinal  tubules,  and  generally  with  the 
interglobular  spaces.  Its  laminae  are  bolted  to- 
gether by  perforating  fibres  like  those  of  ordi- 
nary bone  (Sharpey's  fibres).  Cement  differs 
from  ordinary  bone  in  possessing  no  Haversian 
canals,  or,  if  at  all,  only  in  the  thickest  part. 
Such  canals  are  more,  often  met  with  in  teeth 
with  the  cement  hypertrophied  than  in  the 
normal  tooth. 


Development  of  the  Teeth. 

The  first  step  in  the  development  of  the 
teeth  consists  in  a  downward  growth  (fig.  69, 
1)  from  the  deeper  layer  of  stratified  epi- 
thelium of  the  mucous  membrane  of  the  mouth, 
which  becomes  thickened  in  the  neighbour- 
hood of  the  maxillae  or  jaws  now  in  the 
course  of  formation.  This  process  passes  down- 
ward into  a  recess  of  the  imperfectly  developed 
tissue  of  the  embryonic  jaw.  The  downward 
epithelial  growth  forms  the  common  enamel  or 
dental  germ,  and  its  position  is  indicated  by  a 
slight  groove  in  the  mucous  membrane  of  the 
jaw.  After  this  there  is  an  increased  develop- 
ment at  certain  points  corresponding  to  the 
situations  of  the  future  milk-teeth.  The  com- 
mon enamel  germ  thus  becomes  extended  by 
further  growth  into  a  number  of  special 
enamel  germs  (fig.  70)  corresponding  to 
each  of  the  milk-teeth,  and  connected  to  the  common  germ  by  a 
narrow  neck  (/).  Each  tooth  is  thus  placed  in  its  own  special 
recess  in  the  embryonic  jaw. 

As  these  changes  proceed,  there  grows  up  from  the  underlying 
connective  tissue  into  each  enamel  germ  (fig.  71,  p),  a  distinct 
vascular  papilla  (dental  papilla),  and  upon  it  the  enamel  germ 
becomes  moulded,  and  presents  the  appearance  of  a  cap  of  two 
layers  of  epithelium  separated  by  an  interval  (fig.  71,  /).  Whilst 
part  of  the  subepithelial  tissue  is  elevated  to  form  the  dental 
papilla,  the  part  which  bounds  the  embryonic  teeth  forms  the  dental 


FIG.  68. — Thin  section  of  the 
enamel,  and  a  part  of  the 
dentine.  a,  Cuticular 
pellicle  of  the  enamel 
(Nasmyth's  membrane) ; 
6,  enamel  columns  with 
fissures  between  them 
and  cross  striae ;  c,  larger 
cavities  in  the  enamel, 
communicating  with  the 
extremities  of  some  of 
the  dentinal  tubules  (d). 
X350.  (Kolliker.) 


CH.  V.] 


DEVELOPMENT   OF   THE    TEETH 


FIG.  69. 


Fin.  70. 


sac   (fig.  71,  s);  and  the  rudiment  of   the  jaw  sends  up  processes 
forming  partitions  between  the  teeth.     In  this  way  small  chambers 
are  produced  in   which   the  dental   sacs  are  contained,   and   thus 
the  sockets  of  the  teeth  are 
formed.     The  papilla  is  com- 
posed of  nucleated  cells  ar- 
ranged   in   a    meshwork   of 
connective  tissue,  the  outer  or 
peripheral  part  being  covered 
with    a    layer   of    columnar 
nucleated  cells  called  odonto- 
blasts. 

These  cells,  either  by 
secretion,  or  as  some  think 
by  direct  transformation  of 
the  outer  part  of  each,  form 
a  layer  of  dentinal  matrix 
on  the  apex  of  the  papilla,  or 
if  the  tooth  has  more  than 
one  cusp,  then  at  the  apex 
of  each  cusp.  This  layer  is 
first  uncalcified  (odontogen), 
but  globules  of  calcareous 
matter  soon  appear  in  it. 
These,  becoming  more  numer- 
ous, blend  into  the  first  cap 
of  dentine.  In  the  mean- 
while the  odontoblasts  have 
formed  a  second  layer  of 
odontogen  within  this  (fig. 
72),  and  this  in  turn  becomes 
calcified;  thus  layer  after 
layer  is  formed,  each  extend- 
ing laterally  further  than  its 
predecessor ;  the  layers  blend 
except  in  some  places;  here 
portions  of  odontogen  remain, 

germ.  FIG.  71.— Ala'terstagej'c,  outline  ot epithelium 
of  gum;  /,  neck  of  enamel  germ;  /,  enamel  organ; 
p,  papilla ;  s,  dental  sac  forming  ;  /  p,  the  enamel 
germ  of  permanent  tooth ;  m,  bone  of  jaw ;  v,  vessels 
cut  across.  (Waldeyer  and  Kolliker.) 


down  into  the  mucous  membrane ;  2,  palatine  pro- 
cess of  jaw  ;  3,  Rete  Malpighi.  FIG.  70.— Here  the 
section  passes  through  one  of  the  special  enamel 
germs  which  is  becoming  flask-shaped ;  c,  tf,  epi- 
thelium of  mouth ;  /,  neck  ;  /,  body  of  special  enamel 


which  in  a  tooth  macerated 

for  histological  purposes  get 

destroyed,  and  appear  as  the 

interglolular  spaces  (fig.  66), 

so  called  because  bounded  by  the  deposit  of  calcareous  salts,  which 

occurs,  as  we  have  already  seen,  in  the  form  of  globules. 

As  the  odontoblasts  retire   towards  the  centre,  depositing  layer 
after  layer  of  dentine,  they  leave  behind  them  long  filaments  of  their 


58 


THE   CONNECTIVE  TISSUES 


[CH.  V. 


protoplasm  around  which  the  calcareous  deposit  is  moulded ;  thus  the 
dentinal  tubules  occupied  by  the  processes  of  the  odontoblasts  are 
formed. 

The  other  cells  of  the  dental  papilla  form  the  cells  of  the  pulp. 


FIQ.  72. — Part  of  section  of  developing  tooth  of  a 
young  rat,  showing  the  mode  of  deposition  of 
the  dentine.  Highly  magnified,  a,  Outer 
layer  of  fully  formed  dentine ;  &,  uncalcified 
matrix  with  one  or  two  nodules  of  calcareous 
matter  near  the  calcified  parts ;  c,  odonto- 
blasts sending  processes  into  the  dentine ; 
d,  pulp;  e,  fusiform  or  wedge-shape  cells 
found  between  odontoblasts ;  /,  stellate  cells 
of  pulp  in  fibrous  connective  tissue.  The 
section  is  stained  with  carmine,  which  colours 
the  uncalcified  matrix  but  not  the  calcified 
part.  (E.  A.  Schiifer.) 

Formation  of  the  enamel. — 
The  portion  of  the  enamel  or 
dental  germ  that  covers  the 
dental  papilla  is  at  this  stage 
called  the  enamel  organ.  This 
consists  of  four  parts  (see  figs. 
73  and  74). 

1.  A  layer  of  columnar  epi- 

thelium cells  in  contact  with  the  dentine.     These  are  called 
the  enamel  cells,  adamantoblasts,  or  ameloHasts. 

2.  Two  or  three  layers  of  smaller  polyhedral  nucleated  cells,  the 

stratum  intermedium  of  Hannover. 

3.  A  matrix  of  non-vascular  jelly-like  tissue  containing  stellate 

cells. 

4.  An  outer  membrane  of  several  layers  of  flattened  epithelium 

cells. 

The  first  three  layers  on  an  enlarged  scale  are  seen  in  fig.  74. 

The  enamel  prisms  are  formed  by  the  agency  of  the  ends  of  the 
adamantoblasts  which  abut  on  the  dental  papilla.  Each  forms  a  fine 
deposit  of  globules  staining  with  osmic  acid  and  resembling  keratin 
in  its  resistance  to  mineral  acid.  At  one  time  it  was  believed  that 
ea,ch  adamantoblast  was  itself  calcified  and  converted  into  an  enainej 


FIG.  73. — Vertical  transverse  section  of  the 
dental  sac,  pulp,  etc.,  of  a  kitten,  a,  Dental 
papilla  or  pulp  ;  &,  the  cap  of  dentine  formed 
upon  the  summit ;  c,  its  covering  of  enamel ; 
d,  inner  layer  of  epithelium  of  the  enamel 
organ ;  e,  gelatinous  tissue  ;  /,  outer  epithe- 
lial layer  of  the  enamel  organ ;  g,  inner  layer, 
and  h,  outer  layer  of  dental  sac.  x  14. 
(Thiersch.) 


CH.  V.] 


DEVELOPMENT   OF   THE   TEETH 


59 


prism,  but  this  view  has  been  disproved  by  recent  research.  The 
layer  of  keratin-like  material  is  outside  the  bodies  of  the  cells,  although 
a  process  of  each  adamantoblast  extends  into  it  as  a  tapering  fibre 
(process  of  Tomes),  and  it  is  usually  produced  simultaneously  with 
the  first  layer  of  uncalcified  dentine:  when  it  undergoes  calcifica- 
tion, the  first  layer  of  enamel  is  complete.  The  adamantoblasts 
then  repeat  the  process,  first  causing  a  deposition  of  keratin-like 
material,  and  this  in  turn  is  calcified,  and  so  on.  During  the  forma- 
tion of  layer  after  layer  of  enamel,  the  adamantoblasts  retire.  By 
the  time  the  enamel  is  approaching  completion  the  other  layers 
of  the  enamel  organ  have  almost  disappeared,  and  they  entirely 


FIG.  74. — Highly  magnified  view  of  a  piece  of  the  enamel  organ  in  a  kitten's  canine,  d,  Superficial 
layer  of  dentine,  e,  Newly  formed  enamel  stained  black  by  osmic  acid.  T,  Tomes'  processes  from 
the  adamantoblasts,  ad. ;  str.  int.,  stratum  intermedium  of  the  enamel  organ,  p,  Branched  cells  of 
the  enamel  pulp.  (After  Rose.) 

disappear  when  the  tooth  emerges  through  the  gum.  But  for  some 
little  time  there  is  a  somewhat  more  persistent  membrane  covering 
the  crown ;  this  is  Nasmyth's  membrane,  or  the  enamel  cuticle ;  this 
is  the  last- formed  keratinous  layer  of  enamel  which  has  remained 
uncalcified. 

As  with  the  dentine,  the  formation  of  enamel  appears  first  on  the 
apex  of  each  cusp. 

The  cement  or  crusta  petrosa  is  formed  from  the  internal  tissue  of 
the  tooth  sac,  the  structure  and  function  of  which  are  identical  with 
those  of  the  osteogenetic  layer  of  the  periosteum ;  or,  in  other 
words,  ossification  in  membrane  occurs  in  it. 

The  outer  layer  or  portion  of  the  membrane  of  the  tooth  sac  forms 
the  dental  periosteum. 


60  THE   CONNECTIVE   TISSUES  [CH.  V. 

This  periosteum,  when  the  tooth  is  fully  formed,  is  not  only  a 
means  of  attachment  of  the  tooth  to  its  socket,  but  also  in  conjunction 
with  the  pulp  is  a  source  of  nourishment  to  it.  Additional  laminae  of 
cement  are  added  to  the  root  from  time  to  time  during  the  life  of 
the  tooth  (as  is  especially  well  seen  in  the  abnormal  condition  called 
an  exostosis),  by  the  process  of  ossification  taking  place  in  the  perios- 
teum. On  the  other  hand,  absorption  of  the  root  (such  as  occurs 
when  the  milk-teeth  are  shed)  is  due  to  the  action  of  the  osteoclasts 
of  the  same  membrane. 

In  this  manner  the  first  set,  or  milk-teeth,  are  formed ;  and  each 
tooth,  as  it  grows,  presses  at  length  on  the  wall  of  the  sac  enclosing 
it,  and,  causing  its  absorption,  is  cut,  to  use  a  familiar  phrase. 

The  temporary  or  milk  teeth  are  later  replaced  by  the  growth  of 
the  permanent  teeth,  which  push  their  way  up  from  beneath  them. 

Each  temporary  tooth  is  replaced  by  a  tooth  of  the  permanent  set 
which  is  developed  from  a  small  sac  which  was  originally  an  offshoot 
from  the  sac  of  the  temporary  tooth  which  precedes  it,  and  called  the 
cavity  of  reserve  (fig.  71,  fp).  Thus  the  temporary  incisors  and 
canines  are  succeeded  by  the  corresponding  permanent  ones,  the 
temporary  first  molar  by  the  first  bicuspid;  the  temporary  second 
molar  develops  two  offshoots,  one  for  the  second  bicuspid,  the  other 
for  the  permanent  first  molar.  The  permanent  second  molar  is  budded 
off  from  the  first  permanent  molar,  and  the  wisdom  from  the  perma- 
nent second  molar. 

The  development  of  the  temporary  teeth  commences  about  the 
sixth  week  of  intra-uterine  life,  after  the  laying  down  of  the  bony 
structure  of  the  jaws.  Their  permanent  successors  begin  to  form 
about  ten  weeks  later.  The  second  permanent  molars  originate  about 
the  third  month  after  birth,  and  the  wisdom  teeth  about  the  third  year. 

The  Blood. 

A  full  consideration  of  the  blood  will  come  later,  so  here  we  shall 
only  rapidly  and  briefly  enumerate  its  principal  characters. 

The  blood  is  a  fluid  which  holds  in  suspension  large  numbers  of 
solid  particles  which  are  called  the  corpuscles.  The  fluid  itself  is 
called  the  plasma  or  liquor  sanguinis.  It  is  a  richly  albuminous  fluid ; 
and  one  of  the  proteins  in  it  is  called  fibrinogen. 

After  blood  is  shed  it  rapidly  becomes  viscous,  and  then  sets  into 
a  jelly.  The  jelly  contracts  and  squeezes  out  of  the  clot  a  straw- 
coloured  fluid  called  serum,  in  which  the  shrunken  clot  then  floats. 

The  formation  of  threads  of  a  solid  protein  called  fibrin  from  the 
soluble  protein  called  fibrinogen  is  the  essential  act  of  coagulation ; 
this,  with  the  corpuscles  it  entangles,  forms  the  clot.  Serum  is  plasma 
minus  the  fibrin  which  it  yields.  The  following  scheme  shows  the 
relationships  of  these  constituents  at  a  glance : — 


CH.  V.]  THE   BLOOD  61 

f  Serum 

-r»i     i  f  Plasma  >  Fibrin  |  nl  , 

^Corpuscles  J Clot 

The  corpuscles  are  of  two  chief  kinds,  the  red  and  the  white. 
The  white  corpuscles  are  typical  amoeboid,  nucleated  cells. 

The  red  corpuscles  are  much  more  numerous  than  the  white, 
averaging  in  man  5,000,000  per  cubic  millimetre,  or  400  to  500  red 
to  each  white  corpuscle.  It  is  these  red  corpuscles  that  give  the  red 
colour  to  the  blood.  They  vary  in  size  and  structure  in  different 
groups  of  the  vertebrates.  In  mammals  they  are  biconcave  (except 
in  the  camel  tribe,  where  they  are  biconvex)  non-nucleated  discs,  in 
man  ^V^  inch  in  diameter ;  during  foetal  life  nucleated  red  corpuscles 
are,  however,  found.  In  birds,  reptiles,  amphibians  and  fishes  they 
are  biconvex  oval  discs  with  a  nucleus:  they  are  largest  in  the 
amphibia.  The  most  important  and  abundant  of  the  constituents 
of  the  red  corpuscles  is  the  pigment  which  is  called  hcemoglobin. 
This  is  a  protein-like  substance,  but  is  remarkable  as  it  contains  a 
small  amount  of  iron  (about  0'4  per  cent.). 

The  blood  during  life  is  in  constant  movement.  It  leaves  the 
heart  by  the  vessels  called  arteries,  and  returns  to  the  heart  by  the 
vessels  called  veins ;  the  terminations  of  the  arteries  and  the  com- 
mencements of  the  veins  are,  in  the  tissues,  connected  by  the  thin- 
walled  microscopic  vessels  called  capillaries.  In  the  capillaries, 
leakage  of  the  blood-plasma  occurs ;  this  exuded  fluid  (lymph)  carries 
nutriment  from  the  blood  to  the  tissue-elements,  and  removes  from 
them  the  waste  products  of  their  activity.  The  lymph  is  collected  by 
lymphatic  vessels,  which  converge  to  the  main  lymphatic,  called  the 
thoracic  duct.  This  opens  into  the  large  veins  near  to  their  entrance 
into  the  heart ;  and  thus  the  lymph  is  returned  to  the  blood. 

But  blood  is  also  a  carrier  of  oxygen,  and  it  is  the  pigment 
haemoglobin  which  is  the  oxygen  carrier ;  in  the  lungs  the  haemoglobin 
combines  with  the  oxygen  of  the  air,  and  forms  a  loose  compound  of 
a  bright  scarlet  colour  called  oxyhcemoglobin.  This  arterial  or  oxy- 
genated blood  is  taken  to  the  heart  and  thence  propelled  by  the 
arteries  all  over  the  body,  where  the  tissues  take  the  respiratory 
oxygen  from  the  oxyhsernoglobin,  and  this  removal  of  oxygen  changes 
the  colour  of  blood  to  the  darker  tint  it  has  in  the  veins.  The 
veins  take  the  blood  (minus  a  large  quantity  of  oxygen  and  plus  a 
large  quantity  of  carbonic  acid  received  in  exchange  from  the  tissues) 
to  the  heart,  which  sends  it  to  the  lungs  to  get  rid  of  its  surplus 
carbonic  acid,  and  replenish  its  store  of  oxygen ;  then  the  same  round 
begins  over  again.  It  should,  however,  be  noted  that  haemoglobin 
is  not  a  carrier  of  carbonic  acid;  that  gas  is  carried  mainly  as 
carbonates  in  the  blood-plasma. 


CHAPTER  VI 

MUSCULAR   TISSUE 

MUSCLE  is  popularly  known  as  flesh.  It  possesses  the  power  of  con- 
traction, and  is,  in  the  higher  animals,  the  tissue  by  which  their 
movements  are  executed.  The  muscles  may  be  divided  from  a 
physiological  standpoint  into  two  great  classes — the  voluntary  muscles, 
those  which  are  under  the  control  of  the  will,  and  the  involuntary 
muscles,  those  which  are  not.  The  contraction  of  the  involuntary 
muscles  is,  however,  controlled  by  the  nervous  system,  only  by  a 
different  part  of  the  nervous  system  from  that  which  controls  the 
activity  of  the  voluntary  muscles. 

When  muscular  tissue  is  examined  with  the  microscope,  it  is 
seen  to  be  made  up  of  small,  elongated,  thread-like  structures,  which 
are  called  muscular  fibres  ;  these  are  bound  into  bundles  by  connective 
tissue,  and  in  the  involuntary  muscles  there  is  in  addition  a  certain 
amount  of  cement  substance,  stainable  by  nitrate  of  silver,  between 
the  fibres. 

The  muscular  fibres  are  not  all  alike;  those  of  the  voluntary 
muscles  are  seen  by  the  microscope  to  be  marked  by  alternate  dark 
and  light  stripings  or  striations ;  these  are  called  transversely  striated 
muscular  fibres.  The  involuntary  fibres  have  not  got  these  markings 
as  a  rule.  There  is  one  important  exception  to  this  rule,  namely,  in 
the  case  of  the  heart,  the  muscular  fibres  of  which  are  involuntary, 
but  transversely  striated.  There  are,  however,  histological  differ- 
ences between  cardiac  muscle  and  the  ordinary  voluntary  striated 
muscles.  The  unstriated  involuntary  muscular  fibres  found  in  the 
walls  of  the  stomach,  intestine,  bladder,  blood-vessels,  uterus,  and 
other  contractile  organs  are  generally  spoken  of  as  plain  muscular 
fibres. 

From  the  histological  standpoint  there  are,  therefore,  three 
varieties  of  muscular  fibres  found  in  the  body  of  the  higher 
animals:  two  of  them  are  transversely  striate'd,  and  one  is  not. 
The  relationship  of  this  histological  classification  to  the  physiological 

02 


CH.  VI.]  VOLUNTARY   MUSCLE  63 

classification  into  voluntary  and  involuntary  is  shown  in  the  follow- 
ing table : — 

1.  Transversely  striated  muscular  fibres  : 

a.  In  skeletal  muscle     .         .         .  VOLUNTARY. 

b.  In  cardiac  muscle  \ 

2.  Plain  muscular  fibres  :  , 

In  blood-vessels,  intestine,  uterus,     |          INVOLUNTARY. 
bladder,  etc.          .         .         .         J 

All  kinds  of  muscular  tissue  are  therefore  composed  of  fibres,  but 
the  fibres  are  essentially  different  from  those  we  have  hitherto  studied 
in  the  connective  tissues.  There  the  fibres  are  developed  in  the 
intercellular  material;  here,  in  muscle,  the  fibres  are  developed 
from  the  cells;  that  is,  the  cells  themselves  become  elongated 
to  form  the  muscular  fibres. 


Voluntary  Muscle. 

The  voluntary  muscles  are  those  which  are  sometimes  called 
skeletal,  constituting  the  whole  of  the  muscular  apparatus  attached  to 
the  bones.* 

The  fibres  vary  in  thickness  and  length  a  good  deal,  but  they 
average  -^$  inch  in  diameter,  and  about  1  inch  in  length.  Each 


FIQ.  75.— A  branched  muscular  fibre  from  the  frog's  tongue.    (Kiilliker.) 

fibre  is  cylindrical  in  shape,  with  rounded  ends ;  many  become  pro- 
longed into  tendon  bundles  by  which  the  muscle  is  attached  to 
bone.  As  a  rule  they  are  unbranched,  but  the  muscle  fibres  of  the 
face  and  tongue  divide  into  numerous  branches  before  being  inserted 
to  the  under  surface  of  the  skin,  or  mucous  membrane  (fig.  75). 
The  fibres  in  these  situations  are  also  finer  than  in  the  majority  of 
the  voluntary  muscles. 

Each  fibre  consists  of  a  sheath,  called  the  sarcolemma,  enclosing 
a  soft  material  called  the  contractile  substance.  The  sarcolemma  is 

*  The  muscular  fibres  of  the  pharynx,  part  of  the  (esophagus,  and  of  the 
muscles  of  the  external  ear,  though  not  under  the  control  of  the  will,  have  the 
same  structure  as  the  voluntary  muscular  fibres. 


64 


MUSCULAR   TISSUE 


[CH.  VI. 


homogeneous,  elastic  in  nature,  and  especially  tough  in  fish  and 
amphibia.  It  may  readily  be  demonstrated  in  a  microscopic  prepara- 
tion of  fresh  muscular  fibres  by  applying  gentle  pressure  to  the  cover 
slip;  the  contractile  substance  is  thereby  ruptured,  leaving  the 
sarcolemma  bridging  the  space  (fig.  76).  To  the  sarcolemma  are 
seen  adhering  some  nuclei. 


FIG.  76. — Muscular  fibre  torn  across,  the 
sarcolemma  still  connecting  the  two 
parts  of  the  fibre.  (Todd  and  Bow- 
man.) 

FIG.  77. — Muscular  fibre  of 
a  mammal  highly  mag- 
nified. The  surface  of 
the  fibre  is  accurately 
focussed.  (Schafer.) 

The  contractile    substance   within    the   sheath  is  made   up   of 

alternate  discs  of  dark  and  light  substance. 

Muscular  fibres  contain  oval  nuclei.     In  mammalian  muscle  these 

are  situated  just  beneath  the  sarcolemma ;  but  in  frog's  muscle  they 

occur  also  in  the  thickness  of  the  mus- 
cular fibre.  The  chromoplasm  of  the 
nucleus  has  generally  a  spiral  arrange- 
ment, and  often  there  is  a  little  granular 
protoplasm  (well  seen  in  the  muscular 
fibres  of  the  diaphragm)  around  the  poles 
of  each  nucleus. 

If  the  surface  of  a  fibre  is  carefully 
focussed  with  a  high  power,  rows  of 
apparent  granules  are  seen  lying  at  the 
boundaries  of  the  light  streaks,  and  fine 
longitudinal  lines  passing  through  the 
dark  streaks  may  be  detected  uniting  the 
apparent  granules  (fig.  77). 

In  specimens  treated  with  dilute  acids 
or  gold  chloride,  the  granules  are  seen  to 
be  connected  side  by  side,  or  transversely 
also.  This  reticulum  (fig.  78),  with  its 
longitudinal  and  transverse  meshes,  is 

composed  of  an  interstitial  substance  lying  between  the  essentially 

contractile  portions  of  the  muscle.     A  muscular  fibre  is  thus  made 


FIG.  78. — Portion  of  muscle-fibre  of 
water-beetle,  showing  network 
very  plainly.  One  of  the  trans- 
verse networks  is  split  off,  and 
some  of  the  longitudinal  bars  are 
shown  broken  oft:  (After  Mel- 
land.) 


CH.  VI.] 


VOLUNTARY  MUSCLE 


65 


FIG.  79. — Transverse  section  through 
muscular  fibres  of  human  tongue. 
The  nuclei  are  deeply  stained, 
situated  at  the  inside  of  the  sar- 
colemma.  Each  muscle  fibre 
shows  "Cohnheim's  areas." 
x  450.  (Klein  and  Noble  Smith.) 


up  of  what  are  called  fibrils  or  sarcostyles ;  and  the  longitudinal 
interstitial  substance  with  cross  networks  comprising  the  reticulun) 
just  referred  to  is  called  sarcoplasm.  By 
the  use  of  certain  reagents,  such  as  osmic 
acid  or  alcohol,  the  fibrils  may  be  com- 
pletely separated  from  one  another. 

A  transverse  section  of  a  muscular 
fibre  (fig.  79)  shows  the  sections  of  these 
fibrils;  the  interstitial  sarcoplasm  is  re- 
presented as  white  in  the  drawing.  The 
angular  fields  separated  by  sarcoplasm  may 
still  be  called  by  their  old  name,  areas  of 
Cohnheim. 

If,  instead  of  focussing  the  surface  of 
a  fibre,  it  is  observed  in  its  depth,  a  fine 
dotted  line  is  seen  bisecting  each  light 
stripe;  this  has  been  variously  termed 
Dobie's  line,  or  Krauses  membrane  (fig. 
80).  At  one  time  this  was  believed  to  be 
an  actual  membrane  continuous  with  the  sarcolemma.  It  is  prob- 
ably very  largely  an  optical  effect,  caused  by  light  being  transmitted 
between  discs  of  different  refrangibility. 

If  cross  membranes  do  exist  they  are  not  very  resistant ;  this  was 
well  shown  by  an  accidental  observation  first  made  by  Kuhne,  and 
subsequently  seen  by  others.  A  minute  thread-worm,  called  the 
Myorectes,  was  observed  crawling  up  the  interior  of  the  contractile 
substance  of  a  muscular  fibre;  it  crawled  without  any  opposition 
from  membranes,  and  the  track  it  left,  closed  up  slowly  behind  it 
without  interfering  with  the  normal  cross-striations  of  the  contractile 
substance.  This  observation  strikingly  illustrates  the  fact  that  the 
contractile  substance  in  a  muscular  fibre  is  fluid,  but  only  semi-fluid, 
for  the  closing  of  the  thread-worm's  track  occurred  slowly  as  a  hole 
always  closes  in  a  viscous  material. 

Another  appearance  which  is  sometimes  seen  is  a  fine  clear  line 
running  across  the  fibre  in  the  middle  of  each  dark  band.  It  is 
called  Hensen's  line  or  disc. 

A  muscular  fibre  may  not  only  be  broken  up  into  fibrils,  but 
under  the  influence  of  some  reagents,  such  as  dilute  hydrochloric 
acid,  it  can  be  broken  up  into  discs,  the  cleavage  occurring  in 
the  centre  of  each  light  stripe.  Bowman,  the  earliest  to  study 
muscular  fibres  with  profitable  results,  concluded  that  the  subdivision 
of  a  fibre  into  fibrils  was  a  phenomenon  of  the  same  kind  as  the  cross 
cleavage  into  discs.  He  considered  that  both  were  artificially  pro- 
duced by  a  separation  in  one  or  the  other  direction  of  particles  of  the 
fibre  he  called  "  sarcous  elements."  The  cleavage  into  discs  is  how- 


66 


MUSCULAR   TISSUE 


[CH.  VI. 


ever  much  rarer  than  the  separation  into  fibrils;  indeed,  indications 
of  the  fibrils  are  seen  in  perfectly  fresh  muscle  before  any  reagent 
has  been  added,  and  this  is  markedly  evident  in  the  wing  muscles  of 
many  insects.  It  is  now  believed  that  cleavage  into  discs  is  a 
purely  artificial  phenomenon. 

Haycraft,  who  has  also  investigated  the  question  of  muscular 
structure,  concludes  that  the  cross-striation  is  entirely  due  to  optical 


B 


FIG.  80. — A.  Portion  of  a  human  muscular  fibre,     x  800. 

magnified;  o,  a,  larger,  and  b,  b,  smaller  collections;  c,  still  smaller;  d,  d,  the  smallest  wliic 
could  be  detached,  possibly  representing  a  single  series  of  sarcous  elements.    (Sharpey.) 


1$.   Separated  bundles  of  fibrils  equally 
,  which 


phenomena.  The  fibrils  are  varicose,  and  where  they  are  en- 
larged different  refractive  effects  will  be  produced  from  those 
caused  by  the  intermediate  narrow  portions.  This  view  he  has 
very  ingeniously  supported  by  taking  negative  casts  of  muscular 
fibres  by  pressing  them  on  to  the  surface  of  collodion  films.  The 
collodion  cast  shows  alternate  dark  and  light  bands  Like  the  muscular 
fibres. 

Most  histologists  have  rejected  this  view,  for  the  behaviour  of  the 
dark  stripes  to  various  micro-chemical  and  staining  reagents,  and  to 
polarised  light,  is  different  from  that  of  the  light  stripes.  The 
difference  is  therefore  not  merely  one  of  diameter,  but  of  chemical 
composition. 

The  rapidity  of  muscular  contraction  seems  to  be  proportional 
to  the  clearness  of  the  cross-striation,  and  insects'  muscles  which  are 


CH.  VI.] 


VOLUNTAKY   MUSCLE 


67 


remarkable  for  perfection  of  mechanism  have  consequently  been 
the  subject  of  many  researches.  In  the  wing  muscles  of  these 
animals  the  sarcostyles  are  separated  by  a  considerable  quantity  of 
interstitial  sarcoplasm,  which  may  be  of  nutritive  importance;  at 
any  rate  it  allows  the  intimate  structure  of  the  individual  sarcostyles 
to  be  worked  out  very  thoroughly.  As  the  result  of  such  work, 
Schiifer  has  arrived  at  the  following  conclusions : — 

Each  sarcostyle  is  subdivided  in  the  middle  of  each  light  stripe  by 
transverse  lines  (membranes  of  Krause)  into  successive  portions, 
which  may  be  termed  sar comer es.  Each  sarcomere  is  occupied  by  a 
portion  of  the  dark  stripe  of  the  whole  fibre;  this  portion  of  the 
dark  stripe  may  be  called  a  sarcous  element*  The  sarcous  element 


K -, 


S.B. 


B 


S.K. 


FIG.  81. — Sarcostyles  from  the  wing-muscles 

of  a  wasp. 

A,    A',   Sarcostyles  showing  degrees  of  con- 
traction. 
11,   A  sarcostyle  extended  with  the  sarcous 

elements  separated  into  two  parts, 
c,  Sarcostyles  moderately  extended  (semidia- 
grammatic).    (E.  A.  Schiifer.) 


FIG.  82. — Diagram  of  a  sarcomere 
in  a  moderately  extended  con- 
dition, A,  and  in  a  contracted 
condition,  B. 

K,  K,  Krause's  membranes ;  ji, 
•plane  of  Hensen ;  S.E., 
poriferous  sarcous  ele- 
ment. (E.  A.  Scliiifer.) 


is  really  double,  and  in  the  stretched  fibre  (fig.  81,  B)  separates  into 
two  at  the  line  of  Hensen.  At  either  end  of  the  sarcous  element  is 
a  clear  interval  separating  it  from  Krause's  membrane;  this  clear 
interval  is  more  evident  in  the  extended  sarcomere  (fig.  81,  B),  and 
diminishes  on  contraction  (fig.  81,  A).  The  cause  of  this  is  to  be  found 
in  the  structure  of  the  sarcous  element.  It  is  pervaded  with  longi- 
tudinal canals  or  pores  open  towards  Krause's  membrane,  but  closed 
at  Hensen's  line.  In  the  contracted  muscle  the  clear  part  of  the 
muscle  substance  passes  into  these  pores,  disappears  from  view  to  a 
great  extent,  swells  up  the  sarcous  element,  widens  it,  and  shortens 
the  sarcomere.  In  the  extended  muscle,  on  the  other  hand,  the  clear 
substance  passes  out  from  the  pores  of  the  sarcous  element,  and  lies 

f  Notice  that  this  expression  has  a  different  meaning  from  what  it  originally 
had  when  used  by  Bowman. 


68  MUSCULAR   TISSUE  [CH.  VI. 

between  it  and  the  membrane  of  Krause ;  this  lengthens  and  narrows 
the  sarcomere.*  This  is  shown  in  the  diagrams  (fig.  82).  It  may 
be  added  that  the  sarcous  element  does  not  lie  free  in  the  middle  of 
the  sarcomere,  but  is  attached  at  the  sides  to  a  fine  enclosing 
envelope,  and  at  either  end  to  Krause's  membrane  by  fine  lines 
running  through  the  clear  substance  (fig.  82,  A). 

This  view  is  interesting,  because  it  brings  into  harmony  amoeboid, 
ciliary,  and  muscular  movement.  In  all  three  instances  we  have 
protoplasm  composed  of  two  materials,  spongioplasm  and  hyaloplasm. 
In  amoeboid  movement  the  irregular  arrangement  of  the  spongioplasm 
allows  the  hyaloplasm  to  flow  in  and  out  of  it  in  any  direction.  In 
ciliary  movement  the  flow  is  limited  by  the  arrangement  of  the 
spongioplasm  to  one  direction ;  hence  the  limitation  of  the  movement 
in  one  direction  (see  p.  26).  In  muscle,  also,  the  definite  arrangement 
of  the  spongioplasm  (represented  by  the  sarcous  element)  in  a  longi- 
tudinal direction  limits  the  movement  of  the  hyaloplasm  (represented 
by  the  clear  substance  of  the  light  stripe),  so  that  it  must  flow  either 
in  or  out  in  that  particular  direction.  The  muscular  fibre  is  made  up 
of  sarcostyles,  and  the  sarcostyle  of  sarcomeres.  The  contraction  of 
the  whole  muscle  is  only  the  sum  total  of  the  contraction  of  all  the 
constituent  sarcomeres. 

In  an  ordinary  muscular  fibre  it  is  stated  that  when  it  contracts, 
not  only  does  it  become  thicker  and  shorter,  but  the  light  stripes 
become  dark  and  the  dark  stripes  light.  This  again  is  only  an  optical 
illusion,  and  is  produced  by  the  alterations  in  the  shape  of  the  sarco- 
styles, affecting  the  sarcoplasm  that  lies  between  them.  When  the 
sarcous  elements  swell  during  contraction,  the  sarcoplasm  accumulates 
opposite  the  membranes  of  Krause,  and  diminishes  in  amount  oppo- 
site the  sarcous  elements;  the  accumulation  of  sarcoplasm  in  the 
previously  light  stripes  makes  them  appear  darker  by  contrast  than 
the  dark  stripes  proper.  This  is  shown  in  fig.  83.  There  is  no  true 
reversal  of  the  stripings  in  the  fibrils  themselves. 

That  this  is  the  case  can  be  seen  very  well  when  a  muscular  fibre 
is  examined  with  polarised  light.  A  polarising  microscope  contains 
a  Mcol's  prism  beneath  the  stage  of  the  microscope  which  polarises 
the  light  passing  through  the  object  placed  on  the  stage.  The  eye- 
piece contains  another  Mcol's  prism,  which  detects  this  fact.  If  the 
two  Nicols  are  parallel,  the  light  passing  through  the  first  passes  also 
through  the  second ;  but  if  the  second  is  at  right  angles  to  the  first, 
the  light  cannot  traverse  it,  and  the  field  appears  dark.  If  an  object 
on  the  microscope  stage  is  doubly  refracting  it  will  appear  bright  in 
this  dark  field ;  if  it  remains  dark  it  is  singly  refracting.  The  sarco- 

*  The  existence  of  open  pores  is  not  admitted  by  all  observers.  These  regard 
the  passage  of  fluid  in  and  out  of  the  sarcous  element  as  due  to  diffusion  through 
its  membrane. 


VOLUNTARY   MUSCLE 


69 


CH.  VI.] 

plasm  is  singly  refracting  or  isotropous;  it  remains  dark  in  the 
dark  field  of  the  polarising  microscope.  The  fibrils  or  sarcostyles 
are  in  great  measure  doubly  re- 
fracting or  anisotropous,  and  ap- 
pear bright  in  the  dark  field  of  the 
polarising  microscope.  The  sarco- 
style,  however,  is  not  wholly  doubly 
refracting;  the  sarcous  elements 


it 


Fin.  83. — Wave  of  contraction  passing  over  a  mus- 
cular fibre  of  water-beetle.  R,  R,  Portions  of 
the  fibre  at  rest ;  c,  contracted  part ;  i,  i,  inter- 
mediate condition.  (Schiifer.) 


FIG.  84.— This  figure  (after  Engelmann)  illus- 
trates the  appearance  of  a  muscular  fibre 
as  examined  in  ordinary  light  (left-hand 
side)  and  in  polarised  light  (right-hand 
side).  In  the  upper  part  of  the  diagram 
the  fibre  is  not  contracted,  in  the  lower 
part  it  is  contracted.  The  dark  bands 
are  seen  to  be  bright  by  polarised  light, 
owing  to  their  being  doubly  refracting  or 
anisotropous;  during  contraction,  fluid 
passes  from  the  singly  refracting  or 
isotropous  light  band  into  the  doubly 
refracting  dark  band,  which,  in  conse- 
quence, becomes  widened  out. 


are  doubly  refracting,  and  the  clear  intervals  are  singly  refracting.    On 
contraction  there  is  no  reversal  of  these  appearances,  though  of  course 
the  relative  thickness  of  the  singly  refracting  intervals  varies  inversely 
with  that  of  the  doubly  refracting  sarcous  elements  (see  fig.  84). 
The  meaning  and  causation  of  the  optical  appearances  of  striated 


70 


MUSCULAR   TISSUE 


[CH.  VI. 


FIG.  85.— Three  muscular  fibres 
running  longitudinally,  and 
two  bundles  of  fibres  in  trans- 
verse section,  M,  from  the 
tongue.  The  capillaries,  c, 
are  injected,  x  150.  (Klein 
and  Noble  Smith.) 


muscle  fibres,  and  the  changes  they  undergo  during  contraction 
have  been  the  subjects  of  numerous  hypotheses.  One  of  two  only  of 
these  theories  have  been  mentioned  in  the 
preceding  paragraphs,  and  it  should  be  recog- 
nised that  even  experts  are  content  to  leave 
the  matter  very  largely  an  open  question  at 
present. 

Blood-vessels  of  Muscle. — The  arteries  break 
up  into  capillaries,  which  run  longitudinally 
in  the  intervening  connective  tissue,  trans- 
verse branches  connecting  them  (fig.  85).  No 
blood-vessels  ever  penetrate  the  sarcolemma. 
The  muscular  fibres  are  thus,  like  other  tissues, 
nourished  by  the  exudation  from  the  blood 
called  lymph. 

The  motor  nerves  of  voluntary  muscle  pierce 
the  sarcolemma,  and  terminate  in  expansions 
called  end-plates,  to  be  described  on  p.  78. 

The  sensory  nerves  of  voluntary  muscle 
terminate  in  structures  known  as  the  neuro-muscular  spindles,  which 
will  be  dealt  with  in  the  chapter  on  Motor ial  Sensations. 

Red  Muscles. 

In  many  animals,  such  as  the  rabbit,  and  some  fishes,  most  of  the 
muscles  are  pale,  but  some  few  (like  the  diaphragm,  crureus,  soleus, 
semi-membranosus,  in  the  rabbit)  are  red.  These  muscles  contract 
more  slowly  than  the  pale  muscles,  and  their  red  tint  is  due  to  haemo- 
globin contained  within  their  contractile  substance. 

In  addition  to  these  physiological  distinctions,  there  are  histo- 
logical  differences  between  them  and  ordinary  striped  muscle,  viz. : — 

1.  Their  muscular  fibres  are  thinner. 

2.  They  have  more  sarcoplasm. 

3.  Longitudinal  striation  is  therefore  more  distinct. 

4.  Transverse  striation  is  more  irregular  than  usual. 

5.  Their  nuclei  are  situated  not  only  under  the  sarcolemma,  but 
also  in  the  thickness  of  the  fibre. 

6.  The  transverse  loops  of  the  capillary  network  are  dilated  into 
little  reservoirs,  far  beyond  the  size  of  ordinary  capillaries. 

Cardiac  Muscle. 

The  muscular  fibres  of  the  heart,  unlike  those  of  other  in- 
voluntary muscles,  are  striated ;  but  although  in  this  respect  they 
resemble  the  skeletal  muscles,  they  have  distinguishing  character- 
istics of  their  own.  The  fibres  which  lie  side  by  side  are  united  at 


CH.  VI.] 


CAKDIAC   AND   PLAIN   MUSCLE 


frequent  intervals  by  short  branches  (fig.  86).  The  fibres  are  smaller 
than  those  of  the  ordinary  striated  muscles,  and  their  transverse 
striation  is  less  distinct.  No  sarcolemma 
can  be  discerned.  Each  fibre  has  only  one 
nucleus  which  is  situated  in  the  middle  of 
its  substance.  At  the  junctions  of  the 
fibres  there  is  a  certain  amount  of  cement- 
ing material,  stainable  by  silver  nitrate. 
This  is  bridged  across  by  fine  fibrils  from 
cell  to  cell. 

The  above  is  a  general  description  of 
the  fibres  in  the  great  mass  of  the  oardiac 
musculature.  But  immediately  beneath 
the  lining  membrane  of  the  ventricles, 
and  in  the  main  connecting  strand  which 
links  the  auricles  to  the  ventricles  (the 
auriculo-ventricular  bundle)  are  found 
peculiar  fibres  known  after  their  discoverer  Fl°-  se.— Muscular  fibre-ceils  from 

„       ,  .     .  ,       „,  the  heart.    (E.  A.  Schafer.) 

as  PurkiTije  s  fibres  ;  these  are  large,  clear, 

quadrangular  cells  with  granular  protoplasm  containing  several  nuclei, 
and  striated  only  on  their  margins.  The  special  meaning  and 
function  of  these  fibres  will  be  described  in  the  chapter  on  the  heart. 


FIG.  87. — Muscular  fibre-cells  from  the  muscular  coat  of  intestine — highly  magnified.     Note  the  longi- 
tudinal striation,  and  in  the  broken  fibre  the  sheath  is  visible. 

Plain  Muscle. 

Plain  muscle  forms  the  proper  muscular  coats  (1.)  of  the  digestive 


72  MUSCULAR   TTSSUE  [CH.  VI. 

canal  from  the  middle  of  the  oasophagus  to  the  internal  sphincter 
ani  ;  (2.)  of  the  ureters  and  urinary  bladder  ;  (3.)  of  the  trachea  and 
bronchi  ;  (4.)  of  the  ducts  of  glands  ;  (5.)  of  the  gall-bladder  ;  (6.)  of 
the  vesicuke  seminales  ;  (7.)  of  the  uterus  and  Fallopian  tubes  ;  (8.)  of 
blood-vessels  and  lymphatics  ;  (9.)  of  the  iris,  and  ciliary  muscle  of  the 
eye.  This  form  of  tissue  also  enters  largely  into  the  composition  (10.) 
of  the  tunica  dartos,  the  contraction  of  which  is  the  principal 
cause  of  the  contraction  of  the  scrotum  on  exposure  to  cold.  It 
occurs  also  in  the  skin  generally,  being  found  surrounding  the  secret- 
ing part  of  the  sweat  glands  and  in  small  bundles  attached  to  the  hair 
follicles  ;  it  also  occurs  in  the  areola  of  the  nipple.  It  is  composed  of 
long,  fusiform  cells  (fig.  87),  which  are  not  as  a  rule  more  than 
^o-  inch  long.  Each  cell  has  an  oval  or  rod-shaped  nucleus.  The 
cell  substance  is  longitudinally  but  not  transversely  striated.  Each 
cell  or  fibre,  as  it  may  also  be  termed,  has  a  delicate  sheath.  The 
fibres  are  united  by  cementing  material,  which  can  be  stained  by  silver 
nitrate,  and  is  bridged  across  by  fine  filaments  passing  from  cell  to  cell 
The  nerves  in  involuntary  muscle  (both  cardiac  and  plain)  do  not 
terminate  in  end  -plates,  but  by  plexuses  or  networks,  which  ramify 
between  and  around  the  muscular  fibres. 

Development  of  Muscular  Fibres. 

All  muscular  fibres  (except  those  of  the  sweat  glands,  which  are 
epiblastic)  originate  from  the  mesoblast.  The  plain 
fibres  are  simply  elongated  cells  in  which  the  nucleus 
becomes  rod-shaped.  In  cardiac  muscle,  the  likeness  to 
the  original  cells  from  which  the  fibres  are  formed  is  not 
altogether  lost,  and  this  is  specially  the  case  for  the 
Purkinje's  fibres  alluded  to  on  the  preceding  page. 

Voluntary  muscular  fibres  are  developed  from  cells 
which  become  elongated,  and  the  nuclei  of  which  mul- 
tiply. In  most  striated  muscle  fibres  the  nuclei  ulti- 
mately take  up  a  position  beneath  the  cell-wall  or 
sarcolemma  which  is  formed  on  the  surface.  Stria- 
tions  appear  first  along  one  side,  and  extend  round  the 
fibre  (fig.  88),  then  they  extend  into  the  centre. 

During  life  new  fibres  appear  to  be  formed  in  part 
by  a  longitudinal  splitting  of  pre-existing  fibres  ;  this 
FIG.  ss.  —  Develop-  is  preceded  by  a  multiplication  of  nuclei  ;  and  in  part 
by  the  lengthening  and  differentiation  of  embryonic 


// 


months.      (Ran-  QQ[\S  (sarcoplasts)  f  ound  between  the  fully  formed  fibres. 
In  plain  muscle,  growth  occurs  in  a  similar  way  : 
this  is  well  illustrated  in  the  enlargement  of  the  uterus  during  preg- 
nancy.    After  parturition  the  fibres  shrink  to  their  original  size,  but 
many  disappear  and  are  removed  by  absorption. 


CHAPTEE  VII 

NEBVE 

NERVOUS  tissue  is  the  material  of  which  the  nervous  system  is  com- 
posed. The  nervous  system  is  composed  of  two  parts,  the  central 
nervous  system,  and  the  peripheral  nervous  system.  The  central  nervous 
system  consists  of  the  brain  and  spinal  cord ;  the  peripheral  nervous 
system  consists  of  the  nerves,  which  conduct  the  impulses  to  and  from 
the  central  nervous  system,  and  thus  bring  the  nerve-centres  into 
relationship  with  other  parts  of  the  body. 

Some  of  the  nerves  conduct  impulses  from  the  nerve-centres  and 
are  called  efferent ;  those  which  conduct  impulses  in  the  opposite 
direction  are  called  afferent.  When  one  wishes  to  move  the  hand,  the 
nervous  impulse  starts  in  the  brain  and  passes  down  the  efferent  or 
motor  nerve-tracts  to  the  muscles  of  the  hand,  which  contract;  when 
one  feels  pain  in  the  hand,  afferent  or  sensory  nerve-tracts  convey  an 
impulse  to  the  brain  which  is  there  interpreted  as  a  sensation.  If  all 
the  nerves  going  to  the  hand  are  cut  through,  all  communication 
with  the  nerve-centres  is  destroyed,  and  the  hand  loses  the  power 
of  moving  under  the  influence  of  the  will,  and  the  brain  receives 
no  impulses  from  the  hand,  or,  as  we  say,  the  hand  has  lost 
sensibility. 

This  distinction  between  efferent  and  afferent  nerves  is  a  physio- 
logical one,  which  we  shall  work  out  more  thoroughly  later  on.  No 
histological  distinction  can  be  made  out  between  motor  and  sensory 
nerves,  and  it  is  histological  structure  which  we  wish  to  dwell  upon 
in  this  chapter. 

Under  the  microscope  nervous  tissue  is  found  to  consist  essen- 
tially of  nerve-cells  and  their  branches.  The  nerve-cells  are  contained 
in  the  brain  and  spinal  cord,  and  in  smaller  collections  of  cells  on 
the  course  of  the  nerves  called  ganglia.  The  part  of  the  nerve- 
centres  containing  cells  is  called  grey  matter. 

Long  branches  of  the  nerve- cells  are  known  as  nerve-fibres. 
These  become  sheathed  in  a  manner  to  be  immediately  described, 
and  are  contained  in  the  nerves,  and  in  the  white  matter  of  brain  and 

73 


74 


NERVE 


[cn.  vn. 


spinal  cord, 
arrangement, 


The  bodies   of   nerve-cells   differ   in   size,  shape,  and 

and  we  shall  discuss  these  fully  when  we  get  to  the 

nerve-centres.     For  the  present  it  will  be  convenient 

to  confine  ourselves  to  the  nerve-fibres  as  they  are 

found  in  a  nerve. 

Nerve-fibres  are  of  two  histological  kinds,  medul- 
lated  and  non-medullated.  Medullated  nerve-fibres 
are  found  in  the  white  matter  of  the  nerve-centres 
and  in  the  nerves  originating  from  the  brain  and 
spinal  cord.  Non-medullated  nerve-fibres  occur  in 
the  sympathetic  nerves. 

The  medullated  or  white  fibres  are  characterised 


Fio.  89.  —  Nerve- 
fibre  stained  with 
osmic  acid.  A, 
node ;  B,  nucleus. 
(Key  and  Ret- 
zius.) 


Fio.  90.— A  node  of  Ranvier 
in  a  medullated  nerve-fibre, 
viewed  from  above.  The 
medullary  sheath  is  in- 
terrupted, and  the  primi- 
tive sheath  thickened. 
Copied  from  Axel  Key  and 
Retzius.  x  750.  (Klein 
and  Noble  Smith.) 


Fio.  91.— Axis  cylinder, 
highly  magnified, 
showing  its  com- 
ponent fibrils.  (M. 
Schultze.) 


by  a  sheath  of  white  colour,  fat-like  in  nature,  and 
stained  black  by  osmic  acid ;  it  is  called  the  medullary 
sheath  or  white  substance  of  Schwann ;  this  sheathes  the 
essential  part  of  the  fibre  which  is  a  process  from  a 
nerve-cell,  and  is  called  the  axis  cylinder.  Outside  the 
medullary  sheath  is  a  thin  homogeneous  membrane  of 
elastic  nature  called  the  primitive  sheath  or  neurilemma. 


CH.  VII.  j 


MEDULLATED   NERVE 


75 


The  axis  cylinder  is  a  soft  transparent  thread  in  the  middle  of  the 
fibre;  it  is  made  up  of  exceedingly  fine  fibrils  (fig.  91)  which  stain 
readily  with  gold  chloride.  The  medullary  sheath  gives  a  character- 
istic double  contour  and  tubular  appearance  to  the  fibre.  It  is  inter- 
rupted at  regular  intervals  known  as  the  nodes  of  Ranvier.  The 
stretch  of  a  nerve -fibre  between  two  nodes  is  called  an  inter-node,  and 
in  the  middle  of  each  inter-node  is  a  nucleus  which  belongs  to  the 
primitive  sheath.  Besides  these  interruptions,  a  variable  number  of 
oblique  clefts  are  also  seen  dividing  the  sheath  into  medullary  seg- 
ments (fig.  89) ;  but  most  if  not  all  of  these  are  produced  artificially 
in  the  preparation  of  the  specimen. 

The  medullary  sheath  also  contains  a  horny  substance  called 
neurokeratin :  the  arrangement  of  this  substance  is  in  the  form  of  a 
network  or  reticulum  holding  the  fatty  matter  of  the  sheath  in  its 
meshes.  The  occurrence  of  horny  matter  in  the  epidermis,  in  the 
development  of  the  enamel  of  teeth,  and  in  nerve,  is  an  interesting 
chemical  reminder  that  all  these  tissues  originate  from  the  same 
embryonic  layer,  the  epiblast.  The  fat-like  matter  consists  largely  of 
cholesterin,  a  monatomic  alcohol,  and  phosphorised  fats,  such  as 
lecithin. 

Near  their  terminations  the  nerve-fibres  branch :  the  branching 
occurs  at  a  node  (fig.  92). 


Fio.  92.— Small  branch  of  a  muscular  nerve  of  the  frog,  near  its  termination,  showing  division  of  the 
fibres— a,  into  two  ;  b,  into  three,     x  350.    (Kiilliker.) 

Staining  with  silver  nitrate  produces  a  peculiar  appearance  at  the 
nodes,  forming  what  is  known  as  the  crosses  of  Ranvier. 

One  limb  of  the  cross  is  produced  by  the  dark  staining  of  cement 
substance  which  occurs  between  the  segments  of  the  neurilemma ;  the 
other  limb  of  the  cross  is  due  to  the  staining  of  a  number  of  minute 
transverse  bands  in  the  axis  cylinder  (Fromann's  lines),  which  is  here 


76 


NERVE 


[CH.  VII. 


not  closely  invested  by  the  medullary  sheath  (fig.  93).     Macallum 
has  shown  that  this  appearance  of  transverse  striping  is  an  artifact 


Fio.  93.— Several  fibres  of  a  bundle  of  medullated  nerve-fibres  acted  upon  by  silver  nitrate  to  show 
behaviour  of  nodes  of  Ranvier,  M,  towards  this  reagent.  The  silver  has  penetrated  at  the  nodes, 
and  has  stained  the  axis-cylinder,  M,  for  a  short  distance.  S,  the  white  substance.  (Klein  and 
Noble  Smith.) 

and  can  be  obtained  in  any  exposed  portion  of  an  axis  cylinder,  that 
is,  wherever  the  silver  nitrate  can  penetrate  to  it. 

The  arrangement  of  the  nerve-fibres  in  a  nerve  is  best  seen  in  a 
transverse  section. 


FIG.  94. — Transverse  section  of  the  sciatic  nerve  of  a  cat  about  x  100. — It  consists  of  bundles 
(funiculi)  of  nerve-fibres  ensheathed  in  a  fibrous  sheath,  epineurium,  A  ;  each  bundle  has  a  special 
sheath  (not  sufficiently  marked  out  from  the  epineurium  in  the  figure)  or  perineurium  B ;  the 
nerve-fibres  N  /  are  separated  from  one  another  by  endoneurium ;  L,  lymph  spaces ;  Ar,  artery ; 
V,  vein ;  F,  fat.  Somewhat  diagrammatic.  (V.  D.  Harris.) 

The  nerve  is  composed  of  a  number  of  bundles  or  funiculi  of  nerve- 
fibres  bound  together  by  connective  tissue.     The  sheath  of  the  whole 


CH.  VII.] 


NON-MEDULLATED   FIBRES 


77 


nerve  is  called  the  epineurium ;  that  of  the  funiculi  the  perineurium ; 
that  which  passes  between  the  fibres  in  a  funiculus,  the  endoneurium 
(fig.  94).  Single  nerve-fibres  passing  to  their  destination  are  sur- 
rounded by  a  prolongation  of  the  perineurium,  known  as  the  Sheath 
of  Henle.  The  nerve  trunks  themselves  receive  nerve-fibres  which 
ramify  and  terminate  as  end-bulbs  in  the 
epineurium. 

The  size  of  the  nerve-fibres  varies ; 
the  largest  fibres  are  found  in  the  spinal 
nerves,  where  they  are  14'4  to  19  /*  in 
diameter.*  Others  mixed  with  these 
measure  1*8  to  3 '6  /UL.  These  small  nerve- 
fibres  are  the  visceral  nerves;  they  pass 
to  collections  of  nerve-cells  called  the 
sympathetic  ganglia,  whence  they  emerge 
as  non-medullated  fibres,  and  are  distri- 
buted to  involuntary  muscle.  They  are  well  seen  in  sections  stained 
by  osmic  acid,  the  black  rings  being  the  stained  medullary  sheaths 
(fig.  95). 

The  non-medullated  fibres  or  fibres  of  Remak  have  no  medullary 
sheath,  and  are  therefore  devoid  of  the  double  contour  of  the  medul- 
lated  fibres,  and  are  unaffected  in  appearance  by  osmic  acid.  They 


FIG.  95.— Section  across  a  nerve 
bundle  in  the  second  thoracic 
anterior  root  of  the  dog-,  stained 
with  osmic  acid.  (Gaskell.) 


FIG.  96.— Grey,  or  non-medullated  nerve-fibres.  A.  From  a  branch  of  the  olfactory  nerve  of  the 
sheep ;  two  dark-bordered  or  white  fibres  from  the  fifth  pair  are  associated  with  the  pale  olfactory 
fibres.  B.  From  the  sympathetic  nerve,  x  450.  (Max  Schultze.) 


consist  of  an  axis  cylinder  covered  by  a  nucleated  sheath. 
branch  frequently. 

*  fj.  —  micro-millimetre  =  iVs^  millimetre. 


They 


NERVE 


[Oil.  VII. 


Termination  of  Nerves  in  Muscle. 


In  the  voluntary  muscles  the  motor  nerve-fibres  have  special 
end-organs  called  end-plates  (fig.  97).  The  fibre  branches  two  or 
three  times,  and  each  branch  goes  to  a  muscular  fibre.  Here  the 


Fio.  97,-End-plates  ;  chloride  of  gold  preparation  to  show  the  axis  cylinders  and  their  linal 
ramihcations  of  fibrillw.     x  170.    (Szymonowicz.) 

neurilemma  becomes  continuous  with  the  sarcolemma,  the  medullary 
sheath  stops  short,  and  the  axis  cylinder   branches  several   times. 


Fio.  98.— Termination  of  medullated 
nerve-fibres  in  tendon  near  the  mus- 
cular insertion.  (Golgi.) 


FIG. 


',3*33 

.— One  of  the  reticulated  end-or"ans 
of  fig.  98,  more  highly  magnified.  «. 
Medullated  nerve -fibre;  b,  reticulated 
end-organ.  (Golgi.) 


This  ramification  is  imbedded  in  a  layer  of  granular  protoplasm  con- 
taining numerous  nuclei.     Considerable   variation    in    shape  of  the 


CH.  Vll.j 


DEVELOPMENT   OF   NKRVE    FIBRES 


79 


end-plates  occurs  in  different  parts  of  the  animal  kingdom.  Some- 
what similar  nerve-endings  are  seen  in  tendon ;  these,  however,  are 
doubtless  sensory  (figs.  98,  99). 

In  the  involuntary  muscles,  the  fibres,  which  are  for  the  most  part 
non-medullated,  form  complicated  plexuses  near  their  termination. 
The  plexus  of  Auerbach  (fig.  100)  between  the  muscular  coats  of  the 
intestine  is  a  typical  case.  Groups  of  nerve-cells  will  be  noticed  at 
the  junctions  of  the  fine  nervous  cords.  From  these  plexuses  fine 
branches  pass  off  and  bifurcate  at  frequent  intervals,  until  at  last 
ultimate  fibrillse  are  reached.  These  subdivisions  of  the  axis  cylinders 
do  not  anastomose  with  one  another,  but  they  come  into  close  relation- 


FIG.  100. — Plexus  of  Auerbach,  between  the  two  layers  of  the  muscular  coat  of  the  intestine.    (Cadiat.) 

ship  with  the  involuntary  muscular  fibres ;  though  some  histologists 
have  stated  that  they  end  in  the  nuclei  of  the  muscular  fibres,  it  is 
now  believed  that  they  do  not  pass  into  their  interior. 

The  terminations  of  sensory  nerves  are  in  some  cases  plexuses, 
in  others  special  end-organs.  We  shall  deal  with  these  in  our  study 
of  sensation. 

Development  of  Nerve-fibres. 

A  nerve-fibre  is  primarily  an  outgrowth  from  a  nerve-cell,  as  is 
shown  in  the  accompanying  diagram  (fig.  101).  A  nerve-cell,  though 
it  may  have  many  branches,  only  gives  off  one  process  which  becomes 
the  axis  cylinder  of  a  nerve-fibre.  This  acquires  a  medullary  sheath 


80 


NEEVE 


[CH.  VII. 


when  it  passes  into  the  white  matter  of  the  brain  or  spinal  cord,  and 
a  primitive  sheath  when  it  leaves  the  nerve-centre  and  gets  into  the 
nerve.  But  at  first  the  axis  cylinder  is  not  sheathed  at  all. 

The  formation  of  the  sheaths  is  still  a  matter  of  doubt,  but  the 
generally  accepted  opinion  is  that  the  primitive  sheath  is  formed  by 
mesoblastic  cells  which  become  flattened  out  and  wrapped  round  the 
fibre  end  to  end.  These  are  separated  at  the  nodes  by  intercellular  or 
cement  substance  stainable  by  silver  nitrate  (fig.  93).  The  medullary 
sheath  is  formed,  according  to  some,  by  a  fatty  change  occurring  in 
the  parts  of  these  same  cells  which  are  nearest  to  the  axis  cylinder, 


FIG.  101.— Mul bipolar  nerve-cell  from  anterior  horn  of  spinal  cord ;  a,  axis  cylinder  process. 

Sclmltze.) 


(Max 


but  it  is  much  more  probable  that  it  is  formed  from  the  peripheral 
layer  of  the  axis  cylinder;  the  presence  of  neurokeratin  in  it 
distinctly  points  to  an  epiblastic  origin.  The  fact  also  that,  in  the 
nerve-centres,  the  medullated  nerve-fibres  have  no  primitive  sheath, 
and  the  phenomena  of  Wallerian  degeneration,  to  be  described  later, 
all  tend  to  confirm  the  same  view. 


CHAPTEK  VIII 

IRRITABILITY  AND   CONTRACTILITY 

Irritability  or  Excitability  is  the  power  which  certain  tissues  possess 
of  responding  by  some  change  (transformation  of  energy)  to  the  action 
of  an  external  agent.  This  external  agent  is  called  a  stimulus. 

Undifferentiated  cells  such  as  white  blood-corpuscles  are  irritable ; 
when  stimuli  are  applied  to  them  they  execute  the  movements  we 
have  learnt  to  call  amoeboid. 

Ciliated  epithelium  cells  and  muscular  fibres  are  irritable ;  they 
also  execute  movements  under  the  influence  of  stimuli. 

Nerves  are  irritable ;  when  they  are  stimulated,  a  change  is  pro- 
duced in  them;  this  change  is  propagated  along  the  nerve,  and  is 
called  a  nervous  impulse ;  there  is  no  change  of  form  in  the  nerve 
visible  to  the  highest  powers  of  the  microscope ;  much  more  delicate 
and  sensitive  instruments  than  a  microscope  must  be  employed  to 
obtain  evidence  of  a  change  in  the  nerve ;  it  is  of  a  molecular  nature*. 
But  the  irritability  of  nerve  is  readily  manifested  by  the  results  the 
nervous  impulse  produces  in  the  organ  to  which  it  goes;  thus  the 
stimulation  of  a  motor  nerve  produces  a  nervous  impulse  in  that  nerve 
which,  when  it  reaches  a  muscle,  causes  the  muscle  to  contract: 
stimulation  of  a  sensory  nerve  produces  a  nervous  impulse  in  that 
nerve  which,  when  it  reaches  the  brain,  causes  a  sensation. 

Secreting  glands  are  irritable ;  when  stimulated  they  secrete. 

The  electrical  organs  found  in  many  fishes  such  as  the  electric  eel, 
and  torpedo  ray,  are  irritable ;  when  they  are  stimulated  they  give 
rise  to  an  electrical  discharge. 

Contractility  is  the  power  that  certain  tissues  -possess  of  respond- 
ing to  a  stimulus  by  change  of  form.  Contractility  and  irritability 
do  not  necessarily  go  together;  thus  both  muscle  and  nerve  are 
irritable,  but  of  the  two,  only  muscle  is  contractile. 

Some  movements  visible  to  the  microscope  are  not  due  to  con- 
tractility ;  thus  granules  in  protoplasm  or  in  a  vacuole  may  often  be 
seen  to  exhibit  irregular,  shaking  movements  due  simply  to  vibrations 
transmitted  to  them  from  the  outside.  Such  movement  is  known 
as  Brownian  movement. 

81  F 


82 


IRRITABILITY   AND   CONTRACTILITY 


[Cii.  V1I1. 


Instances  of  contractility  are  seen  in  the  following  cases : — 

1.  The   movements   of   protoplasm    seen   in   simple  animal  and 
vegetable  cells  have  been  already  described  on  pp.  11  to  14. 

2.  The  movements  of  pigment  cells.     These  are  well  seen  under 
the  skin  of  such  an  animal  as  the  frog ;  under  the  influence  of  elec- 
tricity and  of  other  stimuli,  especially  of  light,  the  pigment  granules 
are  massed  together  in  the  body  of  the  cell,  leaving  the  processes 
quite  transparent  (fig.  102).     If  the  stimulus  is  removed  the  granules 
gradually  extend  into   the  processes  again.     Thus  the  skin  of   the 
frog   is   sometimes   uniformly   dusky,   and    sometimes    quite    light 
coloured.     The   chameleon   is  an   animal  which  has  become  almost 
proverbial,  since  it  possesses  the  same  power  to  a  marked  degree. 
This  function  is  a  protective  one ;  the  animal  approximates  in  colour 
that  of  its  surroundings,  and  so  escapes  detection. 

In  the  retina  we  shall  find  a  layer  of  pigment  cells  (fig.  103),  the 


FIG.  102.— Frog's  pigment  cells. 


FIG.  103.— Pigment  cells  from  the  retina.  A.  Cells 
still  cohering,  seen  on  their  surface ;  a,  nu- 
cleus indistinctly  seen.  In  the  other  cells  the 
nucleus  is  concealed  by  the  pigment  granules. 
B.  Two  cells  seen  in  profile ;  a,  the  outer  or 
posterior  part  containing  scarcely  any  pig- 
ment, x  370.  (Henle.) 


granules  in  which  are  capable  of  moving  in  the  protoplasm  in  a  some- 
what similar  way ;  the  normal  stimulus  here  also  is  light. 

3.  Ciliary  movement ;  here  we  have  a  much  more  orderly  move- 
ment which  has  already  been  described  (see  p.  25). 

4.  In  "Vorticellse,  a  spiral  thread  of   protoplasm  in   their  stalk 
enables  them  by  contracting  it  to  lower  the  bell  at  the  end  of  the 
stalk. 

5.  In  certain  of  the  higher  plants,  such  as  the  sensitive  and  carni- 
vorous plants,  movements  of  the  stalks  and  sensitive  hairs  of  the 
leaves  occur  under  the  influence  of  stimuli. 

6.  Muscular  movement.     This  for  the  student  of  human  physio- 
logy is  the  most  important  of  the  series ;  it  is  by  their  muscles  that 
the  higher  animals  (man  included)  execute  most  of  their  movements. 

If  we  contrast  together  amoeboid,  ciliary,  and  muscular  movement, 
we  find  that  they  differ  from  each  other  very  considerably.  Amoeboid 
movement  can  occur  in  any  part  of  an  amoeboid  cell,  and  in  any 
direction.  Ciliary  and  muscular  movement  are  limited  to  one  direc- 


CH.  VIII.]  KHYTHMICALITY  83 

tion ;  but  they  arc  all  essentially  similar,  consisting  of  the  movement 
of  hyaloplasm  in  and  out  of  spongioplasm ;  it  is  the  arrangement  of 
the  spongioplasm  that  limits  and  controls  the  movement  of  the  hyalo- 
plasm (see  also  p.  68). 

Ehythmicality. — In  some  forms  of  movement  there  is  not  only 
order  in  direction,  but  order  in  time  also.  This  is  seen  in  ciliary 
movement,  and  in  many  involuntary  forms  of  muscular  tissue,  such 
as  that  of  the  heart.  Here  periods  of  contraction  alternate  with 
periods  of  rest,  and  this  occurs  at  regular  intervals.  Under  the  influ- 
ence of  certain  saline  solutions,*  voluntary  muscles  may  be  made 
artificially  to  exhibit  rhythmic  contractions. 

A  familiar  instance  of  rhythmic  movement  in  the  inorganic  world 
is  seen  in  a  water-tap  nearly  turned  off  but  dripping ;  water  accumu- 
lates at  the  mouth  of  the  tap  till  the  drop  is  big  enough  to  fall ;  it 
falls,  and  the  process  is  repeated.  If,  instead  of  water,  gum  or 
treacle,  or  some  other  viscous  substance  is  watched  under  similar 
circumstances,  the  drops  fall  much  more  slowly ;  each  drop  has  to  get 
bigger  before  it  possesses  enough  energy  to  fall.  Thus  we  may  get 
different  rates  of  rhythmic  movement.  So  in  the  body,  during 
the  period  of  rest,  the  cilium  or  the  heart  is  accumulating  potential 
energy,  till,  as  it  were,  it  becomes  so  charged  that  it  discharges; 
potential  energy  is  converted  into  kinetic  energy  or  movement. 

When  contraction  travels  as  a  wave  along  muscular  fibres,  or  from 
one  fibre  to  another,  the  term  peristalsis  is  employed.  These 
waves  are  well  seen  in  such  a  muscular  tube  as  the  intestine,  and  are 
instrumental  in  moving  its  contents  along.  The  heart's  contraction  is 
a  more  complicated  peristalsis  occurring  in  a  rhythmic  manner. 

The  question  may  be  first  asked,  what  evidence  there  is  of  irrita- 
bility in  muscle?  May  not  the  irritability  be  a  property  of  the 
nerve-fibres  which  are  distributed  throughout  the  muscle  and  ter- 
minate in  its  fibres  ?  The  doctrine  of  independent  muscular  irrita- 
bility was  enunciated  by  Haller  more  than  a  century  ago,  and  was 
afterwards  keenly  debated.  It  was  "finally  settled  by  the  following 
experiment  of  Claude  Bernard. 

If  a  frog  is  taken  and  its  brain  destroyed  by  pithing,  it  loses  con- 
sciousness, but  the  circulation  goes  on,  and  the  tissues  of  its  body 
retain  their  vitality  for  a  considerable  time.  If  now  a  few  drops  of  a 
solution  of  curare,  the  South  American  arrow  poison,  are  injected 
with  a  small  syringe  under  the  skin  of  its  back,  it  loses  in  a  few  minutes 
all  power  of  movement.  If  next  the  sciatic  or  any  other  nerve  going 

*  Biedermann's  fluid  has  the  following  composition : — Sodium  chloride  5 
grammes,  alkaline  sodium  phosphate  2  gr.,  sodium  carbonate  0'5  gr.,  water  1  litre. 
If  one  end  of  the  sartorius  of  a  curarised  frog  is  dipped  into  this  fluid,  it  contracts 
rhythmically  in  a  manner  analogous  to  the  heart.  A  solution  of  pure  sodium 
chloride  (0'65  per  cent.)  has  a  similar  action. 


84  IRRITABILITY  AND    CONTRACTILITY  [CH.  VIII. 

to  muscle  is  dissected  out  and  stimulated,  no  movement  occurs  in  the 
muscles  to  which  it  is  distributed.  Curare  paralyses  the  end-plates,  so 
that  nervous  impulses  cannot  get  past  them  and  cause  any  effect  on  the 
muscles.  But  if  the  muscles  are  stimulated  themselves,  they  contract. 

Another  proof  that  muscle  possesses  inherent  irritability  was 
adduced  by  Kiihne.  In  part  of  some  of  the  frog's  muscles  (e.g.  part 
of  the  sartorius)  there  are  no  nerves  at  all;  yet  these  parts  are 
irritable  and  contract  when  stimulated. 

The  evidence  of  the  statement  just  made  that  the  poisonous  effect 
of  curare  is  on  the  end-plates  is  the  following: — The  experiment 
described  proves  it  is  not  the  muscles  that  are  paralysed.  It  must 
therefore  be  either  the  nerves,  or  the  links  between  the  nerve-fibres 
and  the  muscular  fibres.  By  a  process  of  exclusion  we  arrive  at  the 
conclusion  that  it  is  these  links,  for  the  following  experiment  shows  it 
is  not  the  nerves.  The  frog  is  pithed  as  before,  and  then  one  of  its 
legs  is  tightly  ligatured  so  as  to  include  everything  except  the  sciatic 
nerve  of  that  leg.  Curare  is  injected  and  soon  spreads  by  the  circu- 
lating blood  all  over  the  body  except  to  the  leg  protected  by  the  liga- 
ture. It  can  get  to  the  sciatic  nerve  of  that  leg  because  that  was  not 
tied  in  with  the  rest.  The  sciatic  nerve  of  the  other  leg  is  now 
dissected  out;  when  the  muscles  supplied  by  it  cease  to  contract 
when  the  nerve  is  stimulated,  the  frog  may  be  considered  to  be  fully 
under  the  influence  of  the  drug.  But  on  stimulating  the  sciatic 
nerve  of  the  protected  limb,  the  muscles  respond  normally;  this 
shows  that  the  nerve  which  has  been  exposed  to  the  action  of  the 
poison  has  not  been  affected  by  it. 

Varieties  of  Stimuli. 

The  normal  stimulus  that  leads  to  muscular  contraction  is  a 
nervous  impulse ;  this  is  converted  into  a  muscular  impulse  (visible 
as  a  contraction)  at  the  end-plates.  This  nervous  impulse  starts  at 
the  nerve-centre,  brain,  or  spinal  cord,  and  travels  down  the  nerve  to 
the  muscle.  In  a  reflex  action  the  nervous  impulse  in  the  nerve- 
centre  is  started  by  a  sensory  impulse  from  the  periphery ;  thus 
when  one  puts  one's  hand  on  something  unpleasantly  hot,  the  hand  is 
removed ;  the  hot  object  causes  a  nervous  impulse  to  travel  to  the 
brain,  and  the  brain  reflects  down  to  the  muscles  of  the  hand  another 
impulse  by  the  motor  nerves  which  causes  the  muscles  to  contract  in 
such  a  manner  as  to  move  the  hand  out  of  the  way. 

But  the  details  of  muscular  contraction  can  be  more  readily 
studied  in  rmiscles  removed  from  the  body  of  such  an  animal  as  the 
frog,  and  made  to  contract  by  artificial  stimuli.  When  we  have  con- 
sidered these,  we  can  return  to  the  lessons  they  teach  us  about  the 
normal  contractions  in  our  own  bodies. 


CH.  VIII.]  VARIETIES   OF   STIMULI  85 

The  first  thing  to  do  is  to  make  from  a  pithed  frog  a  muscle-nerve 
preparation ;  the  muscle  usually  selected  is  the  gastrocnemius,  the 
large  muscle  of  the  calf  of  the  leg,  with  the  sciatic  nerve  attached. 
For  some  experiments  the  sartorius  or  gracilis  may  be  used;  but 
nearly  all  can  be  demonstrated  on  the  gastrocnemius. 

The  tendon  of  the  gastrocnemius  may  be  tied  to  a  lever  with  a 
flag  at  the  end  of  it,  and  thus  its 
contractions  rendered  more  evi- 
dent; the  bone  at  the  other  end 
is  fixed  in  a  clamp.  Stimuli  may 
be  applied  either  to  the  nerve  or 
to  the  muscle.  If  the  stimulus  is 
applied  to  the  nerve,  it  is  called 
indirect  stimulation  ;  the  stimulus 
starts  a  nervous  impulse  which 
travels  to  the  muscle ;  the  muscle 
is  thus  stimulated  as  it  is  in  voluntary  contraction  by  a  nervous 
impulse.  Stimulation  of  the  muscle  itself  is  called  direct  stimulation. 
These  stimuli  may  be : 

1.  Mechanical ;  for  instance  a  pinch  or  blow. 

2.  Chemical ;  for  instance  salt  or  acid  sprinkled  on  the  nerve  or 
muscle. 

3.  Electrical ;  the  constant  or  the  induced  current  may  be  used. 

In  all  cases  the  result  of  the  stimulation  is  muscular  contrac- 
tion. Of  all  methods  of  artificial  stimulation,  the  electrical  is  the 
one  most  generally  employed,  because  it  is  more  under  control 
and  the  strength  and  duration  of  the  stimuli  (shocks)  can  be 
regulated  easily.  We  shall  therefore  have  to  study  some  electrical 
apparatus. 

Chemical  stimuli  are  peculiar,  for  some  which  affect  muscle  do 
not  affect  nerve,  and  vice  versa ;  thus  glycerin  stimulates  nerve,  but 
not  muscle ;  ammonia  stimulates  muscle,  but  not  motor  nerves. 

We  may  regard  stimuli  as  liberators  of  energy ;  muscle  and  nerve 
and  other  irritable  structures  undergo  disturbances  in  consequence  of 
a  stimulus.  The  disturbance  is  some  form  of  movement,  visible 
movement  in  the  case  of  muscle,  molecular  movement  in  the  case  of 
nerve.  A  stimulus  may  be  regarded  as  added  motion.  Sir  William 
Gowers  compares  it  to  the  blow  that  causes  dynamite  to  explode,  or 
the  match  applied  to  a  train  of  gunpowder.  A  very  slight  blow  will 
explode  a  large  quantity  of  dynamite ;  a  very  small  spark  will  fire  a 
long  train  of  gunpowder.  So  in  muscle  or  nerve  the  effect  is  often 
out  of  all  proportion  to  the  strength  of  the  stimulus ;  a  light  touch 
on  the  surface  of  the  body  may  elicit  very  forcible  nervous  and 
muscular  disturbances ;  and  moreover,  the  effect  of  the  stimulus  is 
propagated  along  the  nerve  or  muscle  without  loss. 


86  IRRITABILITY   AND    CONTRACTILITY  [CH.  VIII. 


Contraction  of  Muscle. 

Muscle  undergoes  the  following  changes  when  it  contracts  :— 

1.  Changes  in  form. 

2.  Changes  in  extensibility  and  elasticity. 

3.  Changes  in  temperature. 

4.  Changes  in  electrical  condition. 

5.  Chemical  changes. 

In  brief,  each  of  these  changes  is  as  follows : — 

1.  Changes  inform. — The  muscle  becomes  shorter,  and  at  the  same 
time  thicker.     The  amount  of  shortening  varies  so  that  the  length  of 
the  muscle  when  contracted  is  from  65  to  85  per  cent,  of  what  it  was 
originally.     Up  to  a  certain  point,  increase  of  the  strength  of  the 
stimulus  increases  the  amount  of  contraction.     Fatigue  diminishes, 
and  up  to  about  33°  C.  the  application  of  heat  increases  the  amount 
of  contraction.      Beyond  this  temperature  the  muscular  substance 
begins  to  be  permanently  contracted,  and  a  condition  called  heat  rigor, 
due  to  coagulation  of  the  muscle  proteins,  sets  in  a  little  over  40°  C. 

What  the  muscle  loses  in  length  it  gains  in  width;  there  is  no 
appreciable  change  of  volume. 

Among  the  changes  in  form  must  also  be  mentioned  those  changes 
in  the  individual  muscular  fibres  which  require  a  microscope  for  their 
investigation ;  these  have  been  already  considered  (see  p.  68). 

2.  Changes  in  elasticity  and  extensibility. — The  contracted  muscle 
is  more  stretched  by  a  weight  in  proportion  to  its  length  than  an 
uncontracted    muscle   with   the    same    weight    applied   to   it;    the 
extensibility   of   contracted   muscle  is    increased;    its  elasticity   is 
diminished. 

3.  Changes  in  temperature. — When  muscle  is  at  work  or  contract- 
ing, more  energetic  chemical  changes  are  occurring  than  when  it  is 
at  rest ;  more  heat  is  produced,  and  its  temperature  rises. 

4.  Changes  in  electrical  condition. — A  muscle  when  it  contracts 
undergoes  a  variation  in  its  electrical  condition. 

5.  Chemical  changes. — These  consist  in  an  increased  consumption 
of  oxygen,  and  an  increased  output  of  waste  materials  such  as  car- 
bonic acid,  and   sarcolactic  acid.     After  prolonged  contraction   the 
muscle  consequently  acquires  an  acid  reaction. 

These  five  sets  of  changes  will  form  the  subjects  of  the  following 
five  chapters. 


CHAPTEK   IX 

CHANGS   IN   FORM   IN   A   MUSCLE   WHEN   IT   CONTRACTS 

THOUGH  it  has  been  known  since  the  time  of  Erasistratus  (B.C.  304) 
that  a  muscle  becomes  thicker  and  shorter  when  it  contracts,  it  was 
not  until  the  invention  of  the  graphic  method  by  Ludwig  and  Helm- 
holtz,  about  sixty  years  ago,  that  we  possessed  any  accurate  knowledge 
of  this  change.  The  main  fact  just  stated  may  be  seen  by  simply 
looking  at  a  contracting  muscle,  such  as  the  biceps  of  one's  own  arm ; 
but  more  elaborate  apparatus  is  necessary  for  studying  the  various 
phases  in  contraction  and  the  different  kinds  of  contraction  that  may 
occur. 

These  may  be  readily  demonstrated  on  the  ordinary  muscle-nerve 
preparation  (gastrocnemius  and  sciatic  nerve)  from  a  frog.  By  the 
graphic  method,  one  means  that  the  movement  is  recorded  by  a  writ- 
ing. We  shall  find  that  the  same  method  is  applied  to  the  heart's 
movements,  respiratory  movements,  blood  pressure,  and  many  other 
important  problems  in  physiology.  The  special  branch  of  the  graphic 
method  we  have  now  to  study  is  called  myography ;  the  instrument 
for  writing  is  called  a  myograph ;  the  writing  itself  is  called  a  myogram. 
Put  briefly,  a  myograph  consists  of  a  writing  point  at  the  end  of  a 
lever  attached  to  the  muscle,  and  a  writing  surface  which  travels  at  a 
uniform  rate,  on  which  the  writing  point  inscribes  its  movement. 

The  first  thing,  however,  that  is  wanted  is  something  to  stimulate 
the  muscle  and  make  it  contract ;  the  stimulus  is  usually  applied  to 
the  nerve,  and  the  form  of  stimulus  most  frequently  employed  is 
electrical. 

The  galvanic  battery  in  most  common  use  is  the  Daniell  cell.  It 
consists  of  a  well-amalgamated  zinc  rod  immersed  in  a  cylinder  of 
porous  earthenware  containing  10  per  cent,  sulphuric  acid;  this  is 
contained  within  a  copper  vessel  (represented  as  transparent  for 
diagrammatic  purposes  in  fig.  105)  filled  with  saturated  solution  of 
copper  sulphate.  Each  metal  has  a  binding  screw  attached  to  it,  to 
which  wires  can  be  fastened.  The  zinc  rod  is  called  the  positive 
element,  the  copper  the  negative  element.  The  distal  ends  of  the  wires 

87 


88 


CHANGE   IN   FORM   IN   A   MUSCLE  WHEN   IT   CONTRACTS      [CH.  IX. 


attached  to  these  are  called  poles  or  electrodes,  and  the  pair  of  electrodes 
may  be  conveniently  held  in  a  special  form  of  holder.  The  electrode 
attached  to  the  positive  element  (zinc)  is  called  the  negative  pole  or 

kathode ;  that  attached  to  the  negative  ele- 
ment (copper)  is  called  the  positive  pole  or 
anode.  If  now  the  two  electrodes  are  con- 
nected together,  an  electrical,  galvanic,  or 
constant  current  flows  from  the  copper  to 
the  zinc  outside  the  battery,  and  from  the 
zinc  to  the  copper  through  the  fluids  of  the 
battery ;  if  the  electrodes  are  not  connected 
the  circle  is  broken,  and  no  current  can 
flow  at  all.  If  now  a  nerve  or  muscle  is 
laid  across  the  two  electrodes  the  circuit  is 
completed,  and  it  will  be  noticed  at  the 
moment  of  completion  of  the  circuit  the 
muscle  enters  into  contraction ;  if  the 
muscle  is  lifted  off  the  electrodes,  another  contraction  occurs  at  the 
moment  the  circuit  is  broken.  The  same  thing  is  done  more  con- 
veniently by  means  of  a  key :  figs.  106  and  107  represents  two  common 
forms  of  key.  A  key  is  a  piece  of  apparatus  by  which  the  current 


FIG.  105. — Diagram  of  a  Daniell's 
Battery. 


Fro.  107.— Mercury  Key. 

can  be  allowed  to  pass  or  not 
through  the  nerve  or  muscle  laid 
on  the  electrodes.  When  the  key 
is  open  the  current  is  broken,  as  in 
the  next  figure  (fig.  108);  when  it  is  closed  the  current  is  allowed 
to  pass.  The  opening  of  the  .key  is  called  break  ;  the  closing  of  the 
key  is  called  make.  A  contraction  occurs  only  at  make  and  break, 
not  while  the  current  is  quietly  traversing  the  nerve  or  muscle, 


FIG.  106. — Du  Bois  Reymond's  Key. 


OH.  IX.] 


THE   INDUCTION   COIL 


But  it  will  be  seen  in  the  Du  Bois  Keymond  key  (fig.  106)  that 
there  are  four  binding  screws.  This  key  is  used  as  a  bridge  or  short 
circuiting  key,  and  for  many  reasons  this  is  the  best  way  to  use  it. 
The  next  diagram  (fig.  109)  represents  this  diagrammatically.  The 
two  wires  from  the  battery  go  one  to  each  side  of  the  key ;  the  elec- 
trodes come  off  one  from  each  side  of  the  key.  When  the  key  is  open 
no  current  can  get  across  it,  and  therefore  all  the  current  has  to  go  to 
the  electrodes  with  the  nerve  resting  on  them  ;  but  when  the  key  is 
closed,  the  current  is  cut  off  from  the  nerve,  as  then  practically  all  of 
it  goes  by  the  metal  bridge,  or  short  cut,  back  to  the  battery.  Theo- 
retically a  small  amount  of  current  goes  through  the  nerve ;  but  the 
resistance  of  animal  tissues  to  electrical  currents  is  enormous  as  com- 
pared to  that  of  metal,  and  the  amount  of  electricity  that  flows  through 
a  conductor  is  inversely  proportional  to  the  resistance ;  the  resistance 
in  the  metal  bridge  is  so  small  that  for  all  practical  purposes,  all  the 
current  passes  through  it. 

Another  form  of  electrical  stimulus  is  the  induced  current,  pro- 
duced in  an  induction  coil. 

In  a  battery  of  which  the  metals  are  connected  by  a  wire,  we  have 


FIG.  108. 


FIG.  109. 


seen  that  the  current  in  the  wire  travels  from  the  copper  to  the  zinc ; 
if  we  have  a  key  on  the  course  of  this  wire  the  current  can  be  made 
or  broken  at  will.  If  in  the  neighbourhood  of  this  wire  we  have  a 
second  wire  forming  a  complete  circle,  nothing  whatever  occurs  in  it 
while  the  current  is  flowing  through  the  first  wire,  but  at  the  instant 
of  making  or  breaking  the  current  in  the  first  or  primary  wire,  a 
momentary  electrical  current  occurs  in  the  secondary  wire,  which  is 
called  an  induced  current ;  and  if  the  secondary  wire  is  not  a  complete 
circle,  but  its  two  ends  are  connected  by  a  nerve,  this  induction  shock 
traverses  the  nerve  and  stimulates  it ;  this  causes  a  nervous  impulse 
to  travel  to  the  muscle,  which  in  consequence  contracts. 

If  the  first  and  second  wires  are  coiled  many  times,  the  effect  is 
increased,  because  each  turn  of  the  primary  coil  acts  inductively  on 
each  turn  of  the  secondary  coil. 

The  direction  of  the  current  induced  in  the  secondary  coil  is 
the  same  as  that  of  the  current  in  the  primary  coil  at  the  break ;  in 
the  opposite  direction  at  the  make.  The  nearer  the  secondary  coil 
is  to  the  primary,  the  stronger  are  the  currents  induced  in  the 
former. 


90  CHANGE   IN    FORM    IN    A    MUSCLE    WHEN    IT   CONTRACTS    [CH.  IX. 

Fig.  110  represents  the  Du  Bois  Keymond  coil,  the  one  generally 
employed  in  physiological  experiments ;  c  is  the  primary  coil,  and  d 
and  d'  its  two  ends,  which  are  attached  to  the  battery,  a  key  being 
interposed  for  making  and  breaking ;  g  is  the  secondary  coil,  the  two 
terminals  of  which  are  at  its  far  end ;  to  these  the  electrodes  to  the 
nerve  are  attached ;  the  distance  between  the  two  coils,  and  so  the 
strength  of  the  induction  currents,  can  be  varied  at  will.  It  is  only 
when  the  primary  current  is  made  or  broken,  or  its  intensity  increased 
or  diminished,  that  induction  shocks  occur  in  the  secondary  circuit 
which  stimulate  the  nerve.  When  one  wishes  to  produce  a  rapid 
succession  of  make  and  break  shocks  the  automatic  interrupter  or 


FIG.  110. — Du  Bois  Reymond's  Induction  Coil. 

Wagner's  hammer  seen  at  the  right-hand  end  of  the  diagram  is 
included  in  the  circuit. 

The  next  thing  to  be  noticed  is  that  the  break  effects  are  stronger 
than  the  make  effects ;  this  is  easily  felt  by  placing  the  electrodes 
on  the  tongue.  This  is  due  to  what  is  called  Faraday's  extra 
current.  This  is  a  current  produced  in  the  primary  coil  by  the 
inductive  influence  of  contiguous  turns  of  that  wire  on  each  other ; 
its  direction  is  against  that  of  the  battery  current  at  make,  and  so 
the  make  shock  is  lessened.  At  the  break  the  extra  current  is  of 
such  short  duration  (because  when  the  circuit  is  broken  there  can  be 
no  current  at  all)  that  for  all  practical  purposes  it  may  be  considered 
as  non-existent. 

The  same  difference  of  strength  occurs  alternately  in  the  repeated 
shocks  produced  by  Wagner's  hammer.  Helmholtz,  to  obviate  this, 
introduced  a  modification  now  known  after  him.  It  consists  in 
bridging  the  current  by  a  side  wire,  so  that  the  current  never 


CH.  IX.] 


THE   INDUCTION    COIL 


91 


Key 


entirely  ceases  in  the  primary  coil,  but  is  alternately  strengthened 
and  weakened  by  the  rise  and  fall  of  the  hammer ;  the  strengthening 
corresponds  to  the  ordinary  make,  and  is  weakened  by  the  make 
extra  current,  which  occurs  in  the  opposite  direction  to  the  battery 
current ;  the  break  is  also  incomplete,  and  so  it  is  weakened  by  the 
break  extra  current,  which 
being  in  the  same  direction 
as  the  battery  current  im- 
pedes its  disappearance. 

The  two  next  diagrams 
show  the  way  the  interrupter 
acts.  We  are  supposed  to  be 
looking  at  the  end  of  the 
primary  coil;  the  battery 
wires  are  attached  to  the 
binding  screws  A  and  E  (fig. 
111).  The  current  now  passes 
to  the  primary  coil  by  the 

pillar  on  the  left  and  the  spring  or  handle  of  the  hammer  as  far  as 
the  screw  (C) ;  after  going  round  the  primary  coil,  one  turn  only  of 
which  is  seen,  it  twists  round  a  pillar  of  soft  iron  on  the  right-hand 
side,  and  then  to  the  screw  E  and  back  to  the  battery ;  the  result 
of  a  current  going  around  a  bar  of  soft  iron  is  to  make  it  a  magnet, 
so  it  attracts  the  hammer,  and  draws  the  spring  away  from  the  top 
screw  C,  and  thus  breaks  the  current ;  the  current  ceases,  the  soft 

iron  is  no  longer  a  magnet,  so 
it  releases  the  hammer,  and 
contact  is  restored  by  the 
spring;  then  the  same  thing 
starts  over  again,  and  so  a 
succession  of  break  and 
make  shocks  occurs  alter- 
nately and  automatically. 

In  Helmholtz's  modifica- 
tion (fig.  112)  the  battery 
wires  are  connected  as  before. 
The  interrupter  is  bridged  by 
a  wire  from  B  to  C  (also 
shown  in  fig.  110,  e).  C  is 

raised  out  of  reach,  and  the  lower  screw  F  is  brought  within  reach 
of  the  spring.  Owing  to  the  wire  BC,  the  vibration  of  the  hammer 
never  entirely  breaks  the  current. 

Instead  of  Wagner's  hammer  a  long  vibrating  reed  constructed 
on  the  same  principle  is  often  used.  This  has  the  advantage  that 
the  rate  of  vibration  can  be  varied  at  will  by  means  of  a  sliding 


FIG.  112. 


92  CHANGE   IN   FORM    IN   A   MUSCLE  WHEN   IT   CONTRACTS     [CH.  IX. 

clamp  which  fixes  the  reed,  so  that  different  lengths  of  it  can  be 
made  to  vibrate.  If  a  long  piece  of  reed  vibrates,  it  does  so  slowly, 
and  thus  successive  induction  shocks  at  long  intervals  can  be  sent 
into  the  nerve.  But  if  one  wishes  to  stimulate  a  nerve  more  rapidly, 
the  length  of  reed  allowed  to  vibrate  can  be  shortened. 

In  Ewald's  modification  of  the  coil  there  is  another  simple  method 
of  modifying  the  rate  of  the  interrupter.  But  an  hour  spent  in  the 
laboratory  with  an  induction  coil  and  cell  will  teach  the  student 


FIG.  113. — Myograph  of  von  Helmholtz,  shown  in  an  incomplete  form,  a,  Forceps  for  holding  frog's 
femur ;  b,  gastrocnemius ;  c,  sciatic  nerve ;  d,  scale  -  pan  ;  e,  marker  recording  on  cylinder ;  /, 
counterpoise.  (M'Kendrick.) 

much  more  easily  all  these  facts  than  any  amount  of  reading  and 
description. 

We  can  pass  now  to  the  myograph.  There  are  many  different 
forms  of  this  instrument.  Fig.  113  shows  Helmholtz's  instrument. 

The  bony  origin  of  the  gastrocnemius  is  held  firmly  by  forceps, 
and  the  tendo  Achillis  tied  to  a  weighted  lever ;  the  end  of  the  lever 
is  provided  with  a  writing-point  such  as  a  piece  of  pointed  parch- 
ment; when  the  muscle  contracts  it  pulls  the  lever  up,  and  this 
movement  is  magnified  at  the  end  of  the  lever.  The  writing-point 
scratches  on  a  piece  of  glazed  paper  covered  with  a  layer  of  soot;  the 
paper  is  wrapped  round  a  cylinder.  When  the  lever  goes  up  the 
writing-point  will  mark  an  upstroke ;  when  it  falls  it  will  mark  a 


CH.  IX.] 


MYOGRAPHS 


93 


downstroke,  and  if  the  cylinder  is  travelling,  the  downstroke  will 
be  written  on  a  different  part  of  the  paper  than  the  upstroke ;  thus 
a  muscle  curve  or  myogram  is  obtained.  The  paper  may  then  be 
removed,  varnished,  and  preserved. 

Fig.  114  shows  a  somewhat  different  arrangement. 

The  muscle  is  fixed  horizontally  on  a  piece  of  cork,  B,  one  end 
being  fixed  by  a  pin  thrust  through  the  knee-joint  into  the  cork ;  the 


FIG.  114.— Arrangement  of  the  apparatus  necessary  for  recording  muscle  contractions  with  a  revolving 
cylinder  carrying  smoked  paper.  A,  revolving  cylinder ;  B,  the  muscle  arranged  upon  a  cork- 
covered  board  which  is  capable  of  being  raised  or  lowered  on  the  upright,  which  also  can  be  moved 
along  a  solid  triangular  bar  of  metal  attached  to  the  base  of  the  recording  apparatus — the  tendon  of 
the  gastrocnemius  is  attached  to  the  writing  lever,  properly  weighted,  by  a  ligature.  The 
electrodes  from  the  secondary  coil  pass  to  the  nerve— being,  for  the  sake  of  convenience,  first  of  all 
brought  to  a  short-circuiting  key,  D  (Du  Bois  Reymond's)  ;  C,  the  induction  coil ;  F,  the  battery 
(in  this  fig.  a  bichromate  one)  ;  B,  the  key  (Morse's)  in  the  primary  circuit. 

tendo  Achillis  is  tied  to  a  lever  which  is  weighted  near  its  fulcrum : 
the  lever  is  so  arranged  that  it  rests  on  a  screw  till  the  muscle  begins 
to  contract;  the  muscle  therefore  does  not  feel  the  weight  till  it 
begins  to  contract,  and  gives  a  better  contraction  than  if  it  had  been 
previously  strained  by  the  weight.  This  arrangement  is  called  after- 
loading. 

The  writing  surface  is  again  a  travelling  cylinder  tightly  covered 
with  smoked  glazed  paper.     The  rest  of  the  apparatus  shows  how 


91  CHANGE   IN   FORM   IN   A   MUSCLE   WHEN   IT   CONTRACTS    [CH.  IX. 

cell,  coil,  keys,  and  electrodes  are  applied  with  the  object  of  stimulat- 
ing the  nerve. 

The  key  E  makes  and  breaks  the  primary  circuit,  but  the  effect  is 
only  felt  by  the  muscle-nerve  preparation  when  the  short-circuiting 
key  D  in  the  secondary  circuit  is  opened. 

Instead  of  the  key  E  it  is  better  to  have  what  is  called  a  "  kick- 
over  "  key,  which  the  cylinder  by  means  of  a  bar  projecting  from  it 
knocks  over  and  so  breaks  the  primary  circuit  during  the  course  of  a 
revolution.  The  exact  position  of  the  writing-point  at  the  moment 
of  break,  that  is  the  moment  of  excitation,  can  then  be  marked  on 
the  blackened  paper. 

Besides  the  travelling  cylinder  there  are  other  forms  of  writing 


FIG.  115.— Du  Bois  Raymond's  Spring  Myograph.    (M'Kendrick.) 

surface.  Thus  fig.  115  represents  the  spring  myograph  of  Du  Bois 
Keymond.  Here  a  blackened  glass  plate  is  shot  along  by  the  recoil 
of  a  spring ;  as  it  travels  it  kicks  over  a  key,  and  the  result  of  this, 
the  muscular  contraction,  is  written  on  the  plate. 

The  pendulum  myograph  (fig.  116)  is  another  form.  The  pen- 
dulum carries  a  smoked  glass  plate  upon  which  the  writing-point  of 
the  muscle  lever  is  made  to  mark.  The  break  shock  is  sent  into  the 
muscle-nerve  preparation  by  the  pendulum  in  its  swing  opening  a 
key  in  the  primary  circuit.  This  key  is  shown  on  an  enlarged  scale 
in  BC  (fig.  116). 

To  keep  the  preparation  fresh  during  an  experiment,  it  should  be 
covered  with  a  glass  shade,  the  air  of  which  is  kept  moist  by  means 


CH.  IX.] 


MYOGRAPIIS 


95 


of   wet  blotting-paper.      One  form  of   moist  chamber  is  shown  in 


FIG.  116. — Pendulum  Myograph  and  accessory  parts  (Fick's  pattern).  A,  pivot  upon  which  pendulum 
swings ;  B,  catch  on  lower  end  of  myograph  opening  the  key,  C,  in  its  swing ;  D,  a  spring-catch 
which  retains  myograph,  as  indicated  by  dotted  lines,  and  on  pressing  down  the  handle  of  which 
the  pendulum  swings  along  the  arc  to  D  on  the  left  of  figure,  and  is  caught  by  its  spring. 

The  last  piece  of  apparatus  necessary  is  a  time-marker,  so  that 
the  events  recorded  in  the  myogram  can  be  timed.     The  simplest 


FIG.  117.— Moist  Chamber. 


96  CHANGE  IN   FORM   IN   A   MUSCLE   WHEN   IT   CONTRACTS    [CH.  IX. 

time-marker  is  a  tuning-fork  vibrating  100  times  a  second.  This  is 
struck,  and  by  means  of  a  writing-point  fixed  on  to  one  of  the  prongs 
of  the  fork,  these  vibrations  may  be  written  beneath  the  myogram. 
More  elaborate  forms  of  electrical  time-markers  or  chronographs  are 
frequently  employed. 

The  Simple  Muscle  Curve. 

We  can  now  pass  on  to  results,  and  study  first  the  result  of  a 
single  instantaneous  stimulus  upon  a  muscle.  This  causes  a  single 
or  simple  muscular  contraction,  or,  as  it  is  often  called,  a  twitch.  The 
graphic  record  of  such  a  contraction  is  called  the  simple  muscle  curve. 
One  of  these  is  shown  in  the  accompanying  figure  (fig.  118). 


FIG.  118. — Simple  muscle  curve. 

The  muscle  was  stimulated  by  a  single  induction-shock,  at  the 
instant  marked  P  upon  the  base-line.  The  lower  wavy  line  is  traced 
by  a  tuning-fork  vibrating  100  times  a  second,  and  serves  to  measure 
the  time  occupied  in  each  part  of  the  contraction. 

It  will  be  observed  that  after  the  stimulus  has  been  applied 
there  is  an  interval  before  the  contraction  commences.  This 
interval,  termed  the  latent  period,  when  measured  by  the  tuning- 
fork  tracing  is  seen  to  be  about  T£Q-  sec.  During  the  latent  period 
there  is  no  apparent  change  in  the  muscle. 

The  second  part  is  the  stage  of  contraction  proper.  The  lever 
is  raised  by  the  shortening  of  the  muscle.  The  contraction  is  at  first 
very  rapid,  but  then  progresses  more  slowly  to  its  maximum. 

The  next  stage  is  the  stage  of  elongation.  After  reaching  its 
highest  point,  the  lever  descends  in  consequence  of  the  elongation 
of  the  muscle.  The  small  waves  which  follow  the  main  curve  are 
simply  due  to  the  elasticity  of  the  muscle  and  recording  apparatus, 
and  are  most  marked  when  the  contraction  is  rapid  and  vigorous. 


CH.  IX.]  THE   SIMPLE  MUSCLE   CURVE  97 

The  whole  contraction  occupies  about  ^  of  a  second.  With 
regard  to  the  latent  period,  it  should  be  pointed  out  that  if  the  muscle 
is  stimulated  indirectly,  i.e.,  through  its  nerve,  some  of  the  apparent 
lost  time  is  occupied  in  the  propagation  of  the  nervous  impulse  along 
the  nerve.  To  obtain  the  true  latent  period,  this  must  be  deducted. 
Then  there  is  latency  in  the  apparatus  (friction  of  the  lever,  etc.)  to 
be  taken  into  account.  This  can  be  got  rid  of  by  photographing  the 
contracting  muscle,  on  a  sensitive  photographic  plate  travelling  at 
an  accurately-timed  rate.  By  such  means  it  is  found  that  the  true 
latent  period  is  much  shorter  than  was  formerly  supposed.  It  is 
only  4-^  of  a  second.  In  red  muscles  it  is  longer. 

We  now  come  to  the  action  of  various  factors  in  modifying  the 
character  of  the  simple  muscle  curve. 

1.  Influence  of  strength  of  stimulus. — A  minimal  stimulus  is  that 
which   is  just  strong   enough   to   produce   a    contraction.      If   the 
strength   of   stimulus   is   increased    the   amount   of  contraction   as 
measured  by  the  height  of  the  curve  is  increased,  until  a  certain 
point  is  reached  (maximal  stimulus),  beyond  which  increase  in  the 
stimulus  produces  no  increase  in  the  amount  of  contraction.     The 
latent  period  is  shorter  with  a  strong  than  with  a  weak  stimulus. 

2.  Influence  of  load. — Increase  of  load  decreases  the  amount  of 
contraction,  until  at  last  a  weight  is  reached  which  the  muscle  is 
unable  to  lift.     The  latent  period  is  somewhat  longer  with  a  heavy 
load  than  with  a  light  one. 

3.  Influence  of  fatigue. — This   can   be   very  well  illustrated  by 
letting   the   muscle   write   a   curve   with  every  revolution   of    the 
cylinder,  until  it  ceases   to   contract  at   all.     Fig.   119   shows  the 
result.      At    first    the    contractions    improve,   each    being   a    little 
higher  than  the  preceding ;  this  is  known  as  the  beneficial  effect  of 
contraction,  and  the  graphic  record  is  called  a  staircase.     Then  the 
contractions  get  less  and  less.     But  what  is  most  noticeable  is  that 
the  curves  are  much  more  prolonged ;  the  latent  period  gets  longer ; 
the  period  of  contraction  gets  longer ;  and  the  period  of  relaxation 
gets  very  much  longer ;   this  condition  is  known  as  contracture,  so 
that   the   original   base-line   is   not   reached   by  the  time  the  next 
stimulus  arrives.     In  the  last  stages  of  fatigue,  contracture  passes 
off.     Contracture  is  often  absent  in  fatigue  of  mammalian  muscle. 

4.  Effect  of  temperature. — Cold  at  first  increases  the  height  of 
contraction,  then  diminishes  it ;  otherwise  the  effect  is  very  like  that 
of  fatigue,  increasing  the  duration  of  all  stages  of  the  curve. 

Moderate  warmth  increases  the  height  and  diminishes  the 
duration  of  all  stages  of  the  curve,  latent  period  included.  This  may 
be  readily  shown  by  dropping  salt  solution  *  at  different  tempera- 

*  Physiological  saline  solution  used  for  bathing  living  tissue  is  a  0'9  per  cent, 
solution  of  sodium  chloride  in  ordinary  tap  water. 

G 


98 


CHANGE   IN   FORM    IN    A    MUSCLE   WHEN    IT   CONTRACTS     [CH.  IX. 


CH.  IX.] 


THE   SIMPLE    MUSCLE   CUKVE 


99 


tures  on  to  the  muscle  before  taking  its  curve.  Fig.  120  shows  the 
result  of  such  an  experiment.  Too  great  heat  (above  42°  C.)  induces 
heat  rifjor,  due  to  the  coagulation  of  the  muscle  proteins. 


FIG.  120. — Effect  of  temperature  on  the  simple  niuscie  curve.  The  various  temperatures  are  marked 
on  the  curves.  P  is  the  point  of  stimulation  ;  and  the  time-tracing  again  indicates  hundredths  of 
a  second. 

5..  Effect  of  veratrine. — If  this  is  injected  into  the  frog  before  the 
muscle-nerve  preparation  is  made,  the  very  remarkable  result  seen 


Fio.  121.— Veratrine  curve,  taken   on  a  very  slowly  travelling  cylinder;  the  time-tracing  indicates 
seconds,  not  hundredths  of  a  second  as  in  the  previous  diagrams. 

in    fig.    121    is    produced    on    stimulation;    there    is    an    enormous 


100          CHANGE   IN   FORM    IN   A   MUSCLE   WHEN    IT   CONTRACTS    [CH.  IX. 

prolongation  of  the  period  of  relaxation ;  marked  by  a  secondary 
rise,  and  sometimes  by  tremors.  The  second  rise  has  received 
various  explanations,  none  of  which  can  be  regarded  as  satisfactory. 
After  repeated  stimulation  the  veratrine  effect  passes  off,  but  returns 
after  a  period  of  rest. 

The  Muscle-Wave. 

The  first  part  of  a  muscle  which  contracts  is  the  part  where  the 
nerve-fibres  enter ;  the  nerve  impulses,  however,  are  so  rapidly  carried 
to  all  the  fibres  that  for  practical  purposes  they  all  contract  together. 
But  in  a  nerveless  muscle,  that  is  one  rendered  physiologically  nerve- 
less by  curare,  if  one  end  of  the  muscle  is  stimulated,  the  contraction 
travels  as  a  wave  of  thickening  to  the  other  end  of  the  muscle,  and 
the  rate  of  propagation  of  this  wave  can  be  recorded  graphically. 
The  next  figure  (fig.  122)  represents  one  of  the  numerous  methods 


FIG.  122. — Arrangement  for  tracing  the  muscle-wave.    (M'Kendrick.) 

that  have  been  devised  for  this  purpose.  A  muscle  with  long  parallel 
fibres,  like  the  sartorius,  is  taken ;  it  is  represented  diagrammaticaliy 
in  the  figure.  It  is  stimulated  at  the  end,  where  the  two  wires, 
+  and  — ,  are  placed ;  it  is  grasped  in  two  places  by  pincers,  which 
are  opened  by  the  wave  of  thickening ;  the  opening  of  the  first  pair 
of  pincers  (1)  presses  on  a  drum  or  tambour  connected  to  a  second 
tambour  with  a  recording  lever  (I'),  and  this  lever  goes  up  first ;  the 
lever  (2')  of  the  tambour  connected  with  the  second  pair  of  pincers 
(2)  goes  up  later.  If  the  length  of  muscle  between  the  pairs  of 
pincers  is  measured,  and  by  a  time-tracing  the  delay  in  the  raising 


CH.  IX.]  EFFECTS    OF   SUCCESSIVE   STIMULI  101 

of  the  second  lever  is  ascertained,  we  have  the  arithmetical  data  for 
calculating  the  rate  of  propagation  of  the  muscle-wave.  It  is  about 
3  metres  per  second  in  frog's  muscle,  but  is  hastened  by  warmth  and 
delayed  by  cold  and  fatigue. 

The  Effect  of  Two  successive  Stimuli. 

If  a  second  stimulus  follows  the  first  stimulus  at  a  sufficient 
interval  of  time,  each  will  cause  a  twitch  and  two  simple  muscle 
curves  will  be  written  (fig.  123,  A) ;  the  second  is  a  little  bigger  than 
the  first  (beneficial  effect  of  contraction).  If  the  second  stimulus 
arrives  before  the  muscle  has  finished  contracting  under  the  influence 
of  the  first,  a  second  curve  will  be  added  to  the  first,  as  shown  in 
fig.  123,  B.  This  is  called  superposition,  or  summation  of  effects. 

If  the  two  stimuli  are  in  such  close  succession  that  the  second 
occurs  during  the  latent  period  of  the  first,  the  result  will  differ 
according  as  the  stimuli  are  maximal  or  submaximal.  If  they  are 
maximal,  the  second  stimulus  is  without  effect ;  but  if  submaximal, 
the  two  stimuli  are  added  together,  and  though  producing  a  simple 
muscle  curve,  produce  one  which  is  bigger  than  either  would  have 
produced  separately.  This  is  called  summation  of  stimuli  (fig.  123,  C). 

Effect  of  More  than  Two  Stimuli. 

If  a  succession  of  stimuli  are  sent  into  a  muscle,  or  its  nerve,  the 
results  obtained  depend  on  the  rate  at  which  the  stimuli  follow  one 
another.  If  the  time  intervals  between  the  stimuli  are  sufficiently 
great,  each  stimulus  will  produce  a  simple  muscular  contraction,  and 
one  records  a  succession  of  twitches,  and  the  beneficial  effect  of 
previous  action  is  exhibited  in  what  is  known  as  a  staircase  (fig.  124, 
A  and  B). 

If  the  induction  shocks  follow  each  other  more  rapidly,  the  effect 
is  a  continuation  of  the  superposition  curve  already  described  in 
connection  with  two  successive  stimuli.  Just  as  a  second  stimulus 
adds  its  curve  to  that  written  as  the  result  of  the  first,  so  a  third 
stimulus  superposes  its  effect  on  the  second ;  a  fourth  on  the  third, 
and  so  on.  Each  successive  increment  is,  however,  smaller  than 
the  preceding,  and  at  last  the  muscle  remains  at  a  maximum  con- 
traction, till  it  begins  to  relax  from  fatigue. 

A  succession  of  stimuli  may  be  sent  into  the  nerve  of  a  nerve- 
muscle  preparation  by  means  of  the  Wagner's  hammer  of  a  coil,  or 
the  vibrating  reed  previously  mentioned  (p.  92).  This  method  of 
stimulation  is  called  faradisation.  Fig.  124,  C  to  F,  shows  the  kind 
of  tracings  one  obtains.  The  number  of  contractions  corresponds  to 
the  number  of  stimulations ;  the  condition  of  prolonged  contraction 


FIG.  123.— Effect  of  two  successive  excitations.  The  two  points  of  excitation  (P]  and  P2)  are  marked 
in  each  case  on  the  base-line.  In  A,  P:  and  P.?  are  sufficiently  far  apart  to  give  separate  curves. 
In  B  they  are  nearer  together,  and  superposition  is  seen.  In  C  they  are  sufficiently  near  to  give 
summation  of  stimuli.  Submaximal  stimuli  were  used  throughout ;  and  the  time-tracing  in  each 
case  shows  hundredths  of  a  second. 


CII.  IX. 


COMPOSITION    OF   TETANUS 


103 


.  124.— Composition  of  tetanus.  These  six  tracings  were  obtained  on  a  slowly  moving  drum  from  a 
frog's  gastrocnemius,  which  was  excited  by  a  succession  of  induction  shocks.  By  a  mechanical 
contrivance  the  rate  of  the  vibrating  hammer  which  interrupted  the  primary  circuit  of  the 
inductorium  could  be  easily  varied ;  and  the  rate  of  the  hammer  was  increased  from  about  1  per 
second  in  A  to  30  per  second  in  F.  In  A,  separate  twitches  are  seen;  in  B,  the  rate  was  still 
insufficient  to  cause  fusion  ;  in  both  A  and  B,  the  staircase  effect  is  well  seen.  In  C  and  D,  the 
rate  was  sufficiently  great  to  cause  incomplete  tetanus;  in  E,  tetanus  was  nearly  complete,  and 
in  F  it  is  complete.  The  time-tracing  in  each  case  shows  half-seconds. 


104          CHANGE   IN    FORM    IN    A    MUSCLE   WHEN    IT    CONTRACTS     [CH.  IX. 

so  produced,  the  muscle  never  relaxing  completely  between  the 
individual  contractions  of  which  it  is  made  up,  is  called  tetanus: 
incomplete  tetanus,  when  the  individual  contractions  are  discernible 
(fig.  124,  0,  D,  and  E) ;  complete  tetanus,  as  in  fig.  124,  F,  when  the 
contractions  are  so  jrapid  as  to  be  completely  fused  to  form  a  con- 
tinuous line  without  waves. 

The  rate  of  faradisation  necessary  to  cause  complete  tetanus  varies 
a  good  deal ;  for  frog's  muscle  it  averages  15  to  20  per  second ;  for 
the  pale  muscles  of  the  rabbit,  20  per  second ;  for  the  more  slowly 
contracting  red  muscles  of  the  same  animal,  10  per  second ;  and  for 
the  extremely  slowly  contracting  iraiscles  of  the  tortoise  2  per  second 
is  enough.  With  fatigue  as  the  period  of  relaxation  becomes  pro- 
longed, the  rate  necessary  to  produce  complete  tetanus  is  diminished. 

Voluntary  Tetanus. 

We  have  seen  that  voluntary  muscles  under  the  influence  of 
artificial  stimuli  may  be  made  to  contract  in  two  ways:  a  single 
excitation  causes  a  single  contraction ;  a  rapid  series  of  excitations 
causes  a  series  of  contractions  which  fuse  to  form  tetanus. 

We  now  come  to  the  important  question,  in  which  of  these  two 
ways  does  voluntary  muscle  ordinarily  contract  in  the  body  ?  The 
answer  to  this  is,  that  voluntary  contraction  resembles,  though  it  is 
not  absolutely  identical  with,  tetanus  artificially  produced.  It  is 
certainly  never  a  twitch.  The  nerve-cells  from  which  the  motor 
fibres  originate  do  not  possess  the  power  of  sending  isolated  impulses 
to  the  muscles;  they  send  a  series  of  impulses  which  result  in  a 
muscular  tetanus,  or  voluntary  tetanus,  as  it  may  conveniently  be 
termed. 

If  a  stethoscope  is  placed  over  any  contracting  muscle  of  the 
human  body,  such  as  the  biceps,  a  low  sound  is  heard.  The  tone  of 
this  sound,  which  was  investigated  by  Wollaston,  and  later  by 
Helmholtz,  corresponds  to  thirty-six  vibrations  per  second ;  this  was 
regarded  as  the  first  overtone  of  a  note  of  eighteen  vibrations  per 
second,  and  for  a  long  time  18  per  second  was  believed  to  be  the 
rate  of  voluntary  tetanus. 

The  so-called  "  muscle  sound "  is,  however,  no  indication  of  the 
rate  of  muscular  vibration.  Any  irregular  sound  of  low  intensity 
will  produce  the  same  note ;  it  is,  in  fact,  the  natural  resonance-tone 
of  the  meinbrana  tympani  of  the  ear,  and,  therefore,  selected  by  the 
organ  of  hearing  when  we  listen  to  any  irregular  mixture  of  faint, 
low-pitched  tones  and  noises. 

A  much  more  certain  indication  of  the  rate  of  voluntary  tetanus 
is  obtained  by  the  graphic  method.  The  myographs  hitherto  de- 
scribed are  obviously  inapplicable  to  the  investigation  of  such  a 


CFI.  IX.] 


VOLUNTARY   TETANUS 


105 


problem  in  man.  The  instrument  employed  is  termed  a  transmis- 
sion myograph.  The  next  figure  shows  the  recording  part  of  the 
apparatus. 

It  is  called  a  Mare/s  Tambour.  It  consists  of  a  drum,  on  the 
membrane  of  which  is  a  metallic  disc  fastened  near  one  end  of  a 
lever,  the  far  extremity  of  which  carries  a  writing  point.  The  interior 
of  the  drum  is  connected  by  an  india-rubber  tube  (seen  at  the  right- 
hand  end  of  the  drawing)  to  a  second  tambour  called  the  receiving 

Screw  to  regulate  elevation  of  lever 


i 

Writing  lever.  Tambour.  Tube  to  receiving 

tambour. 

FIG.  125. — Marey's  Tambour,  to  which  the  movement  of  the  column  of  air  in  the  n'rst  tambour  is 
conducted  by  a  tube,  and  from  which  it  is  communicated  by  the  lever  to  a  revolving  cylinder,  so 
that  the  tracing  of  the  movement  is  obtained. 

tambour,  in  which  the  writing  lever  is  absent.  Now  if  the  receiving 
tambour  is  held  in  the  hand,  and  the  thumb  presses  on  the  metallic 
disc  on  the  surface  of  its  membrane,  the  air  within  it  is  set  into 
vibrations  of  the  same  rate  as  those  occurring  in  the  thumb  muscles ; 
and  these  are  propagated  to  the  recording  tambour  and  are  written 
in  a  magnified  form  by  the  end  of  the  lever  on  a  recording  travelling 
surface. 

The  tracing  obtained  is  that  of  an  incomplete  tetanus,  which  by  a 


FIG.  126. — Tracing  of  a  voluntary  contraction  of  the  opponeus  pollicis  on  a  slowly  moving  drum,  by 
means  of  the  transmission  myograph.  The  vertical  lines  indicate  seconds.  (Schiifer,  Canney,  and 
Tunstall.) 

time-marker  can  be  seen  to  be  made  up  of  10  to  12  vibrations  a 
second.     A  typical  tracing  is  shown  in  the  above  figure  (fig.  126). 


100          CHANGE   IN    FORM    IN    A    MUSCLE    WHEN    IT    CONTRACTS     [CH.  IX. 

In  some  diseases  these  tremors  are  much  increased,  as  in  the 
clonic  convulsions  of  epilepsy,  or  those  produced  by  strychnine 
poisoning,  but  the  rate  is  the  same. 

Similar  tracings  can  be  obtained  in  an  anaesthetised  animal  by 
strapping  the  receiving  tambour  on  the  surface  of  a  muscle,  and 
causing  it  to  contract  by  stimulating  the  brain  or  spinal  cord.  The 
rate  of  stimulation  makes  no  difference;  however  slow  or  fast  the 
stimuli  occur,  the  nerve-colls  of  the  central  nervous  system  give  out 
impulses  at  their  own  normal  rate. 

The  same  is  seen  in  a  reflex  action.  If  a  tracing  is  taken  from 
a  frog's  gastrocnemius,  the  muscle  being  left  in  connection  with 
the  rest  of  the  body,  its  tendon  only  being  severed  and  tied  to  a 
lever,  and  if  the  sciatic  nerve  of  the  other  leg  is  cut  through, 
and  the  end  attached  to  the  spinal  cord  is  stimulated,  an  impulse 
passes  up  to  the  cells  of  the  cord,  and  is  then  reflected  down 
to  the  gastrocnemius,  under  observation.  The  impulse  has  thus 
to  traverse  nerve-cells;  the  rate  of  stimulation  then  makes  no 
difference;  the  reflex  contraction  occurs  at  the  same  rate,  10  or  12 
per  second. 

But  now  a  difficulty  arises ;  if  a  twitch  only  occupies  TV  of  a 
second,  there  would  be  time  for  ten  complete  twitches  in  a  second  ; 
they  would  not  fuse  to  form  even  an  incomplete  tetanus.  There  must 
be  some  means  by  which  each  individual  contraction  can  bo  lengthened 
till  it  fuses  with  the  next  contraction,  or  else  each  component  part 
of  the  contraction  is  itself  composite ;  recent  experiments  by  Piper 
indicate  that  the  latter  explanation  is  the  true  one;  he  found 
that  each  wave  of  the  curve  obtained  by  the  graphic  method  is 
really  itself  due  to  fusion  of  contractions  occurring  at  a  more  rapid 
rate.  The  method  he  employed  was  to  count  the  number  of  electrical 
variations  which  accompany  a  voluntary  contraction,  on  the  assump- 
tion that  each  fundamental  unit  of  the  contraction  has  an  electrical 
change  as  its  concomitant.  This  can  be  accomplished  by  the  use  of  a 
very  delicate  galvanometer  (the  string  galvanometer,  p.  121),  the 
movements  of  which  can  be  photographed  on  a  rapidly  travelling 
plate.  The  number  of  electrical  variations  is  then  found  to  be  a 
ttxed  one  for  each  muscle,  but  to  vary  in  different  muscles.  Various 
spinal  and  cranial  motor  centres  have  thus  different  rhythms,  and 
of  those  hitherto  studied  the  cells  of  the  motor  fibres  of  the  fifth 
cranial  nerve  have  the  highest  rate  of  discharge,  86  to  100  per 
second.  In  muscles  supplied  by  spinal  nerves  the  rate  is  lower, 
40  to  60. 

Lever  Systems. — The  arrangement  of  the  muscles,  tendons,  and 
bones  presents  examples  of  the  three  systems  of  levers  which  will  be 
known  to  anyone  who  has  studied  mechanics ;  the  student  of  anatomy 
will  have  no  difficulty  in  finding  examples  of  all  three  systems  in 


CIT.  IX.]  COORDINATION  107 

the  body.  What  is  most  striking  is  that  the  majority  of  cases  are 
levers  of  the  third  kind,  in  which  there  is  a  loss  of  the  mechanical 
power  of  a  lever,  though  a  gain  in  the  rapidity  and  extent  of  the 
movement. 

Most  muscular  acts  involve  the  action  of  several  muscles,  often 
of  many  muscles.  The  acts  of  walking  and  running  are  examples  of 
very  complicated  muscular  actions  in  which  it  is  necessary  not  only 
that  many  muscles  should  take  part,  but  also  must  do  so  in  their 
proper  order  and  in  due  relation  to  the  action  of  auxiliary  and 
antagonistic  muscles.  This  harmony  in  a  complicated  muscular 
action  is  called  coordination. 

By  the  device  of  taking  instantaneous  photographs  at  rapidly 
repeated  intervals  during  a  muscular  act,  the  details  of  different 
modes  of  locomotion  in  man  and  other  animals  have  been  very 
thoroughly  worked  out.  With  this  branch  of  research  the  name 
of  Prof.  Marey  is  intimately  associated. 


CHAPTEE  X 

EXTENSIBILITY,   ELASTICITY,   AND   WORK   OF   MUSCLE 

MUSCLE  is  both  extensible  and  elastic.  It  is  stretched  by  a  weight, 
that  is,  it  possesses  extensibility ;  when  the  weight  is  taken  off,  it 
returns  to  its  original  length,  that  is,  it  possesses  elasticity.  The  two 
properties  do  not  necessarily  go  together ;  thus  a  piece  of  putty  is 
very  extensible,  but  it  is  not  elastic ;  a  piece  of  steel  or  a  ball  of 
ivory  are  only  slightly  extensible,  but  after  the  stretching  force  has 
been  removed  they  return  to  their  original  size  and  shape  very 
perfectly. 

A  substance  is  said  to  be  strongly  elastic,  when  it  offers  a  great 
resistance  to  external  forces ;  steel  and  ivory  are  strongly  elastic. 

A  substance  is  said  to  be  perfectly  elastic,  when  its  return  to  its 
original  shape  is  absolute ;  again  steel  and  ivory  may  be  quoted  as 
examples. 

Muscle  is  very  extensible,  i.e.,  it  is  easily  stretched ;  it  is  feebly 
elastic,  i.e.,  it  opposes  no  great  resistance  to  external  force;  it  is, 
however,  perfectly  elastic;  that  is,  it  returns  to  its  original  shape 
very  exactly  after  stretching.  This  is  true  in  the  case  of  living  muscle 
within  the  body,  but  after  very  great  stretching  even  in  the  body, 
and  still  more  so  after  removal  from  the  body,  when  it  begins  to 
undergo  degenerative  changes  culminating  in  death,  its  elasticity  is 
less  perfect. 

The  cohesion  of  muscular  tissue  is  less  than  that  of  tendon. 
E.  Weber  stated  that  a  frog's  muscle  one  centimetre  square  in 
transverse  section  will  support  a  weight  of  a  kilogramme  (over 
2  Ibs.)  without  rupture,  but  this  diminishes  as  the  muscle  gradually 
dies. 

The  extensibility  of  any  material  may  be  studied  and  recorded  b} 
measuring  the  increase  of  length  which  occurs  when  that  material  is 
loaded  with  different  weights.  In  Helmholtz's  myograph  (fig.  113), 
different  weights  may  be  placed  in  the  scale-pan  beneath  the  muscle, 
and  the  increase  of  length  recorded  on  a  stationary  blackened  cylinder 
by  the  downward  movement  of  the  writing-point ;  the  cylinder  may 

108 


CH.  X.] 


CURVES   OF   EXTENSIBILITY 


109 


then  be  moved  on  a  short  distance,  more  weight  added,  and  the 
additional  increase  of  length  similarly  recorded,  and  so  on  for  a 
succession  of  weights. 

If  this  experiment  is  done  with  some  non-living  substance,  like 
a  steel  spring  or  a  piece  of  india-rubber,  instead  of  a  living  muscle, 
it  is  found  that  the  amount  of  stretching  is  proportional  to  the  weight ; 
a  weight  =  2  produces  an  extension  twice  as  great  as  that  produced 
by  a  weight  =  1 ;  in  this  way  one  obtains  a  tracing  like  that  seen  on 
the  left  hand  of  figure  127,  and  the  dotted  line  drawn  through  the 
lowest  points  of  the  extensions  is  a  straight  one. 


Elastic  Band 


Muscle 


FIG.  127.— (After  Waller.) 

With  muscle,  however,  this  is  different ;  each  successive  addition 
of  the  same  weight  produces  smaller  and  smaller  increments  of  ex- 
tension, and  the  dotted  line  obtained  is  a  curve. 

A  continuous  curve  of  extensibility  may  be  obtained  by  placing 
a  gradually  and  steadily  increasing  force  beneath  the  muscle  instead 
of  a  succession  of  weights  added  at  intervals.  The  most  convenient 
way  of  doing  this  is  to  use  a  steel  spring,  which  is  gradually  and 
steadily  extended;  and  the  writing-point  connected  to  the  muscle 
inscribes  its  excursion  on  a  slowly  moving  cylinder.  If,  then,  after 
the  muscle  has  been  stretched,  the  steel  spring  is  gradually  and 
steadily  relaxed,  the  muscle  retracts  and  again  writes  a  curve  now  in 
the  reverse  direction,  until  it  regains  its  original  length.*  But  in 
muscles  removed  from  the  body,  unless  they  are  very  slightly  loaded, 
the  return  to  the  original  length  is  never  complete;  the  muscle  is 

*  A  mathematical  examination  of  these  curves  shows  that  they  are  not  rect- 
angular hyperbolas  as  they  were  once  considered.  They  are  very  variable  in  form, 
and  cannot  be  identified  with  any  known  mathematical  curve. 


110  EXTENSIBILITY,    ELASTICITY,    AND    WORK    OF   MUSCLE        [CH.  X. 

permanently  longer  to  a  slight  extent,  which  varies  with  the  amount 
of  the  previous  loading. 

If  the  muscle  is  slowly  loaded  and  slowly  unloaded,  the  curvature 
of  its  tracing  is  much  more  marked  than  if  the  experiment  is  done 
rapidly. 

The  following  three  tracings  are  reproduced  from  some  obtained 
by  Dr  Brodie.  In  the  method  used,  the  records  are  not  complicated 
by  the  curve  of  a  lever,  but  the  movement  was  simply  magnified  by 
a  beam  of  light  falling  on  a  mirror  attached  to  the  end  of  the  muscle, 
and  reflected  on  to  a  travelling  photographic  plate.  Each  tracing  is 
to  be  read  from  right  to  left ;  the  first  one  (A)  shows  the  result  of 
stretching  a  steel  spring  by  a  steadily  increasing  force ;  the  end  of 

the  spring  gets  lower  and  lower, 
and  describes  a  straight  line;  at 

^^^^^  ^^^^^  ^^^^^^    the  apex  of  the  tracing  unloading 
B9§B&^^H7£^^^^I    began  and  went   on   steadily  till 

the  spring  once  more  regained  its 
initial  length.  The  upstroke,  like 
the  downstroke,  is  a  straight  line. 
In  B  and  C  muscles  were  used ; 
it  will  be  noticed  that  the  muscle 
does  not  regain  its  original  length 
after  unloading  is  completed,  and 
the  upward  tendency  of  the  tracing 

jj&^ISr^S  ^      beyond  this  point  represents  after- 

retraction.  In  B,  the  extension 
was  applied  rapidly,  the  tracing 
is  almost  a  straight  line;  in  C, 
the  extension  was  brought  about 
more  slowly,  and  the  tracing  is  a 

__^^_  ^^^^^_^^^__       curve;  in  both  cases  the   tracing 
-  BSfESBfcfe^V^^^^^I    °^  the  period  of  unloading  shows 

more  curvature. 

This  introduces  us  to  what  is 

Fio.  123.— Curves  of  extensibility.    (Brodie.)  ,,     ,          ,, 

called  after-extension  and  after- 
retraction.  That  is  to  say,  after  a  muscle  is  weighted  there  is  an 
immediate  elongation,  followed  by  a  gradual  elongation  which 
continues  for  some  time ;  or  if  a  muscle  has  been  weighted  and  is 
then  unloaded  there  is  an  immediate  slackening,  followed  by  a 
gradual  after-retraction. 

This  may  be  shown  by  looking  at  the  graphic  records  shown  in 
the  next  diagram.  It  will  be  noticed  that  the  extension  is  greatest 
when  the  muscle  is  in  a  contracted  condition,  and  smallest  when  it  is 
dead  (in  rigor).  In  fatigue  the  after-extension  is  very  marked,  and 
the  return  after  unloading  very  imperfect. 


CH.  X.] 


CURVES    OF   EXTENSIBILITY 


111 


We  may  now  give  the  results  of  an  actual  experiment ;  a  muscle 
was  loaded  with  successive  weights  of  50,  100,  150,  etc.,  grammes, 
and  its  length  carefully  measured  in  centimetres. 


Load  .... 
Total  extension  .  . 
Increment  of  extension 


50 


100 
6 


150 


200 
9-5 
1-5 


250 
10 
0-5 


300 

10-3 

0-3 


in  rigo 


In  tetanus 


Normal 


Figure  129  shows  that  the  contracted  muscle  is  more  extensible 
than  the  uncontracted  muscle.  This  may  be  still  further  illustrated 
by  an  example  given  on  the  following 
page  in  the  form  of  a  diagram. 

The  thick  lines  represent  the  con- 
tracted muscle,  the  thin  ones  the  un- 
contracted. It  is  represented  as  being 
stretched  by  different  weights  indicated 
along  the  top  line;  and  the  lengths 
under  the  influence  of  these  weights 
are  separated  by  equal  distances. 
Thus  A  C  represents  the  length  of  the 
uncontracted  muscle,  A  B  of  the  con- 
tracted muscle  when  unloaded.  A'  C' 
and  A'  B'  the  same  under  the  influence 
of  a  weight  of  50  grammes,  and  so  on. 

The  curve  connecting  the  ends  of 
the  lengths  of  the  contracted  muscle 
falls  faster  than  that  obtained  from 
the  uncontracted  one,  until  at  the 
point  P  under  the  influence  of  a  weight 
of  250  grammes,  the  two  curves  meet ; 
that  is  to  say,  250  grammes  is  the 
weight  which  the  muscle  was  just  un- 
able to  lift.  Suppose  a  muscle  has  to 
lift  the  weight  of  200  grammes,  it 
begins  with  a  length  A"  C",  but  when 
it  contracts  it  ha.c  ,-j,  length  A"  B",  that 
is,  it  has  contracted  a  distance  of  B"  C", 
which  is  very  small;  when  it  has  to 
lift  a  less  weight  it  shortens  more, 
when  a  greater  weight  it  shortens  less ;  till  when  it  shortens  least  it 
lifts  the  greatest  weight. 

This  experiment  illustrates  the  general  truth  that  when  a  muscle 
is  contracted  it  is  more  extensible.  At  the  point  P  the  energy 
tending  to  shorten  the  muscle  (its  contractile  power)  is  exactly  equal 
to  the  energy  tending  to  lengthen  it  against  its  elastic  force.  Thus 
we  have  the  apparent  paradox  at  this  point,  that  a  muscle  when 


Fatigued 


FIG.  129.— Extensibility  of  muscle  in 
different  states  ;  tested  by  50  grammes 
applied  for  short  pertain.  Tracings 
to  be  read  from  left  to  right.  (After 
Waller.) 


112  EXTENSIBILITY,   ELASTICITY,   AND   WORK   OF   MUSCLB          [CH.  X. 


contracted  has  exactly  the  same  length  as  when  uncontracted ;  but 
this  is  a  matter  of  everyday  experience ;  if  one  tries  to  lift  a  weight 
beyond  one's  strength,  one  fails  to  raise  it,  but  nevertheless  one's 
muscles  have  been  contracting  in  the  effort ;  they  have  not  contracted 
in  the  restricted  sense  of  becoming  shorter,  but  that  is  not  the  only 
change  a  muscle  undergoes  when  it  contracts;  the  other  changes, 
electrical,  thermal,  chemical,  etc.,  have  taken  place,  as  evidenced  in 
one's  own  person  by  the  fact  that  the  individual  has  got  warm  in  his 
efforts,  or  may  even  feel  fatigue  afterwards. 

But  the  paradox  does  not  end  here,  for  if  diagram  130  is  again 
looked  at,  it  will  be  seen  that  beyond  the  point  P  the  two  curves 
cross ;  in  other  words,  the  muscle  may  even  elongate,  due  to  increase 
of  extensibility,  when  it  contracts.  This  is  known  after  its  discoverer 
as  Weber's  paradox.  The  increase  of  extensibility  of  muscle  during 


100 


150 


200 


250 


Contracted 
Uncontracted  --I- 


FIG.  130. 

contraction  is  protective  and  tends  to  prevent  rupture  in  efforts  to 
raise  heavy  weights. 

Influence  of  Temperature  on  Extensibility. — If  a  piece  of  iced 
india-rubber  is  taken  and  stretched  by  a  weight,  its  retractility  when 
the  weight  is  removed  is  very  small.  If,  now,  when  the  weight  is  on 
it,  it  is  warmed  at  one  point,  as  by  placing  the  hand  on  it,  its 
retractility  is  increased  and  it  contracts,  raising  the  weight.  Some 
physiologists  have  considered  that  muscular  contraction  can  be 
explained  in  this  way ;  they  have  supposed  that  the  heat  formed  in 
muscular  contraction  acts  like  warmth  -as  applied  to  india-rubber. 
This  view  is,  however,  incorrect.  It  is  much  more  probable  that 
there  is  no  causal  relationship  between  the  temperature-change  and 
the  extensibility-change  which  occur  when  muscle  contracts;  both 
are  simultaneously  produced  by  the  stimulus. 

Moreover,  the  influence  of  heat  on  muscle  is  by  no  means  the 
same  as  that  on  india-rubber.  This  influence  is  not  invariable,  and 


CH.  X.]  MUSCULAR   WORK  113 

at  certain  temperatures  near  the  freezing-point,  and  under  the 
influence  of  certain  weights,  actual  elongation  may  occur  when  the 
temperature  is  raised. 

Muscular  Tonus. 

In  the  living  animal,  muscles  are  more  or  less  stretched,  but 
never  taut  between  their  two  attachments.  They  are  in  a  state  of 
tonicity  or  tonus,  and  when  divided  they  contract  and  the  two  parts 
separate.  Thus  a  muscle,  even  at  rest,  is  in  a  favourable  condition 
to  contract  without  losing  time  or  energy  in  taking  in  slack. 

Muscular  tonus  is  under  the  control  of  the  nervous  system  (on 
the  reflex  character  of  this  control,  see  later,  under  Tendon  Keflexes) ; 
the  muscles  lengthen  when  their  nerves  are  divided,  or  when  they 
are  rendered  physiologically  nerveless  by  curare.  Besides  the  nervous 
system,  the  state  of  muscular  nutrition  dependent  on  a  due  supply 
of  healthy  blood  must  also  be  reckoned  as  important  in  maintaining 
muscular  tonus. 

Work  of  Muscle. 

The  question  of  muscular  work  is  intimately  associated  with  that 
of  elasticity.  In  a  technical  sense,  work  (W)  is  the  product  of  the 
load  (/)  and  the  height  (A)  to  which  it  is  raised.  W  =  lxh. 

Thus  in  fig.  130,  when  the  muscle  is  unloaded  the  work  done  is 
nil:  W  =  BCxO  =  0.  When  the  load  is  250,  again  the  work  done 
is  nil,  because  then  h  =  0.  With  the  load  50,  W  =  B'  C'x  50. 

If  the  height  is  measured  in  feet  and  the  load  in  pounds,  work  is 
expressed  in  terms  of  foot-pounds.  If  the  height  is  measured  in 


FIG.  131.— Diagram  to  show  the  mode  of  measuring  muscle  work.    (M'Kendrick.) 

millimetres  or  metres,  and  the  load  in  grammes,  the  work  is  expressed 
in  gramme-millimetres  or  gramme-metres  respectively. 

This  may  be  shown  diagrammatically  by  marking  on  a  horizontal 
base  line  or  abscissa,  distances  proportionate  to  different  weights, 
and  vertical  lines  (ordinates)  drawn  through  these  represent  the 
height  to  which  they  are  lifted  (see  fig.  131). 

In  the  diagram  (fig.  131)  the  figures  along  the  base  line  represent 
grammes,  and  the  figures  ajong  the  vertical  line  represent  milli- 
metres. The  work  done  as  indicated  by  the  first  line  is  10  x  5  =  50 

II 


114  EXTENSIBILITY,    ELASTICITY,   AND    WORK    OF   MUSCLE          [CH.  X. 


gramme-millimetres,  the  next  20x6  =  120  gramme-millimetres,  and 
so  on,  while  the  last  on  the  right,  100  x  3  =  300  gramme-millimetres. 
It  is  thus  seen  that  the  height  of  a  muscle-curve  is  no  measure  of  the 
work  done  by  the  muscle  unless  the  weight  lifted  is  taken  into 
account  as  well. 

The  following  figures  are  taken  from  an  actual  experiment  done 
with  the  frog's  gastrocnemius  (Weber) : — 


Weight  lifted. 

Height. 

Work  done. 

5  grammes 

27-6 

millimetres 

138  gramme-millimetres 

15 

25-1 

376 

25 

11-45 

286 

30 

7'3 

" 

219 

FIG.  132. — Dynamometer. 


The  work  increases  with  the  weight  up  to  a  certain  maximum, 
after  which  a  diminution  occurs,  more  or  less  rapidly,  according  as 
the  muscle  is  fatigued. 

Similar  experiments  have  been  made  in  human  beings,  weights 
being  lifted  by  the  calf  muscles,  or  elbow  muscles,  leverage  being 

allowed  for.  In  the  higher 
animals  the  energy  so  ob- 
tained compared  with  the  frog 
is  about  twice  as  great  for 
the  same  volume  of  muscular 
tissue. 

Fig.  132  represents  a  com- 
mon form  of  dynamometer  for 
clinical  use,  employed  in  test- 
ing the  muscles  of  the  arms 
and  hands.  It  is  squeezed  by  the  hand,  and  an  index  represents 
kilogrammes  of  pressure. 

The  muscle,  regarded  as  a  machine,  is  sometimes  compared  to 
artificial  machines  like  a  steam-engine.  A  steam-engine  is  supplied 
with  fuel,  the  latent  energy  of  which  is  transformed  into  work  and 
heat.  The  carbon  of  the  coal  unites  with  oxygen  to  form  carbonic 
acid,  and  it  is  in  this  process  of  combustion  or  oxidation  that  heat 
and  work  are  liberated.  Although  the  analogy  between  muscle  and 
a  steam-engine  is  by  no  means  an  exact  one  (see  more  fully  p.  397), 
nevertheless  it  may  stand  for  our  present  purpose.  In  a  steam- 
engine  a  good  deal  of  fuel  is  consumed,  but  there  is  great  economy 
in  the  consumption  of  the  living  muscular  material.  Take  the 
work  done  by  a  gramme  (about  15  grains)  of  muscle  in  raising  a 
weight  of  4  grammes  to  the  height  of  4  metres  (about  13  feet) ;  in 


CH.  X.]  MUSCULAR   WORK  115 

doing  this  work  probably  less  than  a  thousandth  part  of  the  muscle 
has  been  consumed. 

Next  let  us  consider  the  relationship  between  the  work  and  the 
heat  produced.  An  ordinary  locomotive  wastes  about  96  per  cent,  of 
its  available  energy  as  heat,  only  4  per  cent,  being  represented  as 
work.  In  the  best  triple-expansion  steam-engine  the  work  done  rises 
to  12*5  per  cent,  of  the  total  energy. 

In  muscle,  various  experimenters  give  different  numbers.  Thus, 
Fick  calculated  that  33  per  cent,  of  the  mechanical  energy  is  avail- 
able as  work ;  later  he  found  this  estimate  too  high,  and  stated  the 
number  as  25 ;  Chauveau  gives  12  to  15 ;  M'Kendrick  17.  Thus 
muscle  is  a  little  more  economical  than  the  best  steam-engines ;  but 
the  muscle  has  this  great  advantage  over  any  engine,  for  the  heat  it 
produces  is  not  wasted,  but  is  used  for  keeping  up  the  body  tempera- 
ture, the  fall  of  which  below  a  certain  point  would  lead  to  death,  not 
only  of  the  muscles  but  of  the  body  generally. 

So  far  we  have  been  speaking  as  though  the  only  active  phase  of  muscular  con- 
traction is  the  period  of  shortening.  It  is,  however,  extremely  probable  that 
lengthening  is  also  an  active  process.  This  was  originally  mooted  by  Fick,  who 
pointed  out  that  the  fall  of  a  muscle  lever  during  the  relaxation  period  is  of  variable 
speed,  and  is  obviously  not  due  to  the  passive  elongation  of  the  muscle  by  gravity ; 
the  way  in  which  this  part  of  the  curve  is  varied  by  such  agencies  as  temperature, 
and  drugs  like  veratrine,  also  indicates  that  relaxation  is  an  independent  process. 

Isotonic  and  Isometric  Curves. — If,  in  recording  the  contraction  of  a  muscle,  the 
load  is  applied  vertically  under  the  muscle,  its  pull  upon  the  muscle  varies  during 
the  successive  stages  of  a  single  contraction,  owing  to  the  inertia  of  the  load.  In 
order  to  avoid  this  variation  in  tension,  it  is  usual  to  apply  the  weight  at  a  point 
close  to  the  fulcrum  of  the  recording  lever,  so  that  when  the  lever  is  raised,  the 
weight  remains  practically  stationary,  and  thus  the  error  due  to  its  inertia  is  avoided. 
In  order  to  apply  the  necessary  tension  to  the  muscle,  the  weight  hanging  on  the 
lever  must  be  increased  in  the  ratio  of  the  distances  of  the  muscle  and  weight  from 
the  fulcrum.  A  twitch  recorded  under  such  circumstances  is  called  isotonic,  i.e.,  one 
in  which  the  tension  remains  constant  throughout.  If,  on  the  other  hand,  the 
muscle  is  fixed  at  both  ends,  and  then  excited,  the  resulting  activity  expresses  itself 
in  a  phase  of  increasing  tension  followed  by  one  of  decreasing  tension.  If  the 
alterations  of  tension  are  recorded,  we  obtain  what  is  called  an  isometric  curve. 
This  curve  is  obtained  by  making  the  muscle  pull  against  a  spring  which  is  so  strong 
that  the  muscle  can  only  move  it  to  a  very  slight  extent.  This  slight  movement  is 
then  highly  magnified.  The  curve  thus  obtained  resembles  in  its  main  features  an 
isotonic  contraction,  but  its  maximum  is  reached  earlier,  and  it  returns  to  the  zero 
position  sooner.  The  flat  top  of  the  isometric  curve  described  by  the  earlier 
observers  was  due  to  the  imperfection  of  the  instruments  employed.  The  tracings 
of  muscle  curves  given  in  previous  illustrations  (see  figs.  118  to  124)  were  obtained 
by  the  isotonic  method,  but  it  is  probable  that  the  isometric  curve  is  a  more  faithful 
record  of  the  variations  in  the  intensity  of  the  contraction  process  than  that  yielded 
by  the  isotonic  method.  The  momentum  or  swing  of  a  light  lever  such  as  is  used 
for  obtaining  isotonic  curves  will  no  doubt  account  for  the  extra  upward  movement 
it  executes.  The  whole  matter  has  been  keenly  discussed,  and  the  foregoing  view 
is  that  expressed  by  Kaiser.  Schenk,  on  the  other  hand,  maintains  what  appears  to 
be  an  improbable  idea,  that  there  arc  really  two  kinds  of  change  in  muscle,  which 
account  for  the  difference  obtained  by  the  two  methods. 


CHAPTER  XI 

THE   ELECTRICAL  PHENOMENA   OF  MUSCLE 

WE  have  seen  that  the  chemical  processes  occurring  in  muscular  con- 
traction lead  to  a  transformation  of  energy  into  work  and  heat. 
These  changes  are  accompanied  by  electrical  disturbances  also. 

The  history  of  animal  electricity  forms  one  of  the  most  fascinat- 
ing of  chapters  in  physiological  discovery.  It  dates  from  1786, 
when  G-alvani  made  his  first  observations.  G-alvani  was  Professor  of 
Anatomy  and  Physiology  at  the  University  of  Bologna,  and  his  wife 
was  one  day  preparing  some  frog's  legs  for  dinner,  when  she  noticed 
that  the  apparently  dead  legs  became  convulsed  when  sparks  were 
emitted  from  a  frictional  electrical  machine  which  stood  by.  Galvani 
then  wished  to  try  the  effect  of  lightning  and  atmospheric  electricity 
on  animal  tissues.  So  he  hung  up  some  frogs'  legs  to  the  iron  trellis- 
work  round  the  roof  of  his  house  by  means  of  copper  hooks,  and  saw 
that  they  contracted  whenever  the  wind  blew  them  against  the  iron. 
He  imagined  this  to  be  due  to  electricity  secreted  by  the  animal 
tissues,  and  this  new  principle  was  called  Galvanism.  But  all  his 
contemporaries  did  not  agree  with  this  idea,  and  most  prominent 
among  his  opponents  was  Volta,  Professor  of  Physics  at  another 
Italian  university,  Pavia.  He  showed  that  the  muscular  contractions 
were  not  due  to  animal  electricity,  but  to  artificial  electricity  pro- 
duced by  contact  with  different  metals. 

The  controversy  was  a  keen  and  lengthy  one,  and  was  terminated 
by  the  death  of  Galvani  in  1798.  Before  he  died,  however,  he  gave 
to  the  world  the  experiment  known  as  "  contraction  without  metals," 
which  we  shall  study  presently,  and  which  conclusively  proved  the 
existence  of  animal  electricity.  Volta,  however,  never  believed  in  it. 
In  his  hand  electricity  took  a  physical  turn,  and  the  year  after 
Galvani's  death  he  invented  the  Voltaic  pile,  the  progenitor  of  our 
modern  batteries.  Volta  was  right  in  maintaining  that  galvanism 
can  be  produced  independently  of  animals,  but  wrong  in  denying  that 
electrical  currents  could  be  obtained  from  animal  tissues.  Galvani 
was  right  in  maintaining  the  existence  of  animal  electricity,  but 

116 


en.  XT.] 


THE   GALVANOMETER 


117 


wrong  in  supposing  that  the  contact  of  dissimilar  metals  with  tissues 
proved  his  point. 

This  conclusion  has  been  arrived  at  by  certain  new  methods  of 
investigation.  In  1820  Oersted  discovered  electro-magnetism :  that 
is,  when  a  galvanic  current  passes  along  a  wire  near  a  magnetic 
needle,  the  needle  is  deflected  one  way  or  the  other,  according  to 
the  direction  of  the  current.  This  led  to  the  invention  of  the 
astatic  needle  and  the  galvanometer,  an  instrument  by  which  very 
weak  electrical  currents  can  be  detected.  For  a  long  time  the  subject 
of  animal  electricity,  however,  fell  largely  into  disrepute,  because  of 
the  quackery  that  grew  up  around  it.  It  is  not  entirely  free  from 
this  evil  nowadays ;  but  the  scientific  investigation  of  the  subject  has 
led  to  a  considerable  increase  of  knowledge,  and  among  the  names 
of  modern  physiologists  associated  with  it  must  be  particularly 
mentioned  those  of  Du  Bois  Eeymond  and  Hermann. 

Before  we  can  study  these  it  is,  however,  necessary  that  we  should 
understand  the  instruments  employed. 

The  Galvanometer. — The  essential  part  of  a  galvanometer  is  a 
magnetic  needle  suspended  by  a  delicate  thread ;  a  wire  coils  round 


Fio.  133. 


FIG.  134. 


it;  and  if  a  current  flows  through  the  wire,  the  needle  is  deflected. 
Suppose  a  man  to  be  swimming  with  the  current  with  his  face  to  the 
needle,  the  north-seeking  pole  is  turned  to  the  left  hand.  But  such  a 
simple  instrument  as  that  shown  in  fig.  133  would  not  detect  the  feeble 
currents  obtained  from  animal  tissues.  It  is  necessary  to  increase 
the  delicacy  of  the  apparatus,  and  this  is  done  in  several  ways.  In 
the  first  place,  the  needle  must  be  rendered  astatic,  that  is,  independent 
of  the  earth's  magnetism.  The  simplest  way  of  doing  this  is  to  fix 
two  needles  together  (as  shown  in  fig.  134),  the  north  pole  of  one 
pointing  the  same  way  as  the  south  pole  of  the  other.  The  current 
is  led  over  one  needle  and  then  over  the  other ;  the  effect  is  to  pro- 
duce a  deflection  in  each  in  the  same  direction,  and  so  the  sensitive- 
ness of  the  instrument  is  doubled.  If  now  the  wire  is  coiled  not  only 
once,  but  twice  or  more  in  the  same  position,  each  coil  has  its  effect 


118 


THE   ELECTRICAL   PHENOMENA   OF  MUSCLE 


[CH.  XL 


on  the  needles ;  the  multiplication  of  the  effect  of  a  weak  current  in 
this  way  is  accomplished  in  actual  galvanometers  by  many  hundreds 
of  turns  of  fine  wire. 

Fig.  135  illustrates  the  best  galvanometer  of  this  type:  that  of 
Sir  William  Thomson  (afterwards  Lord 
Kelvin).  It  is  called  a  reflecting  galvan- 
ometer, because  the  observer  does  not  actu- 
ally watch  the  moving  needle,  but  a  spot 
of  light  reflected  on  to  a  scale  from  a  little 
mirror,  which  is  attached  to  and  moves 
with  the  needle.  A  very  small  movement 
of  the  needle  is  rendered  evident,  because 
the  movement  of  the  spot  of  light  being,  as 
it  were,  at  the  end  of  a  long  lever — namely, 
the  beam  of  light,  magnifies  it. 


Fin.  135.— Reflecting  galvanometer.  (Thomson.)  A.  The  gal- 
vanometer consists  of  two  systems  of  small  astatic  needles 
suspended  by  a  tine  hair  from  a  support,  so  that  each  set 
of  needles  is  within  a  coil  of  fine  insulated  copper  wire,  that 
forming  the  lower  coil  being  wound  in  an  opposite  direction 
to  the  upper.  Attached  to  the  upper  set  of  needles  is  a 
small  mirror  about  \  inch  in  diameter ;  the  light  from  the 
lamp  at  B  is  thrown  upon  this  little  mirror,  and  is  reflected 
upon  the  scale  on  the  other  side  of  B,  not  shown  in  the  iigure. 
The  coils  u  I  are  arranged  upon  brass  uprights,  and  their 
ends  are  carried  to  the  binding  screws.  The  whole  appar- 
atus is  placed  upon  a  vulcanite  plate  capable  of  being 
levelled  by  the  screw  supports,  and  is  covered  by  a  brass- 
bound  glass  shade,  the  cover  of  which  is  also  of  brass,  and 
supports  a  brass  rod  b,  on  which  moves  a  weak  curved 
magnet  m.  C  is  the  shunt  by  means  of  which  the  amount  of 
the  current  sent  into  the  galvanometer  may  be  regulated. 
When  in  use  the  scale  is  placed  about  three  feet  from  the 
galvanometer,  which  is  arranged  east  and  west,  the  lamp  is 
lighted,  the  mirror  is  made  to  swing,  and  the  light  from  the 
lamp  is  adjusted  to  fall  upon  it,  and  it  is  then  regulated 
until  the  reflected  spot  of  light  from  it  falls  upon  the  zero 
of  the  scale.  The  wires  from  the  non-polarisable  electrodes 
touching  the  muscle  are  attached  to  the  outer  binding 
screws  of  the  galvanometer,  a  key  intervening  for  short  circuiting,  or  if  a  portion  only  of  the 
current  is  to  pass  into  the  galvanometer,  the  shunt  should  intervene  as  well  with  the  appropriate 
plug  in.  When  a  current  passes  into  the  galvanometer  the  needles  and,  with  them,  the  mirror, 
are  turned  to  the  right  or  left  according  to  the  direction  of  the  current.  The  amount  of  the  deflec- 
tion of  the  needle  is  marked  on  the  scale  by  the  spot  of  light  travelling  along  it. 

Non-polarisable    Electrodes, — If  a  galvanometer  is   connected 


en.  XT.] 


NON-rOLARTSABLE   ELECTRODES 


119 


with  a  muscle  by  wires  which  touch  the  muscle,  electrical  currents 
are  obtained  in  the  circuit  which  are  set  up  by  the  contact  of  metal 
with  muscle.  The  currents  so  obtained  form  no  evidence  of  electro- 
motive force  in  the  muscle  itself.  It  is 
therefore  necessary  that  the  wires  from  the 
galvanometer  should  have  interposed  be- 
tween them  and  the  muscle  some  form  of 
electrodes  which  are  non-polarisable.  Fig. 
136  shows  one  of  the  earliest  non-polaris- 
able electrodes  of  Du  Bois  Eeymond.  It 
consists  of  a  zinc  trough  on  a  vulcanite  base. 
The  inner  surface  of  the  trough  is  amalga- 
mated and  nearly  filled  with  a  saturated  so- 
lution of  zinc  sulphate.  In  the  trough  is 
placed  a  cushion  of  blotting-paper,  which 
projects  over  the  edge  of  the  trough;  on  it  there  is  a  pad  of  china 
clay  or  kaolin,  moistened  with  physiological  salt  solution  (0*9  per 
cent,  sodium  chloride);  on  this  pad  one  end  of  the  muscle  rests. 
The  binding  screw  (&)  connects  the  instrument  to  the  galvanometer ; 
the  other  end,  or  some  other  part  of  the  same  muscle,  is  connected 
by  another  non-polarisable  electrode  in  the  same  way  to  the  other 
side  of  the  galvanometer.  If  there  is  any  electrical  difference  of 


FIG.  136.— Non-polarisable  elec- 
trode of  Du  Bois  Reymond. 
(M'Kendrick.) 


FIG.  137.  -Diagram  of  Du  Bois  Reymond's  non-polarisable;electrodes.  a,  Glass  tube  filled  with  a  satu- 
rated solution  of  zinc  sulphate,  in  the  end,  c,  of  which  is  china  clay  drawn  out  to  a  point ;  the  clay 
is  moistened  with  physiological  salt  solution  ;  in  the  solution  of  zinc  sulphate  a  well  amalgamated 
zinc  rod  is  immersed  and  connected,  by  means  of  the  wire  A,  with  the  galvanometer.  The 
remainder  of  the  apparatus  is  simply  for  convenience  of  application.  The  muscle  and  the  end  of 
the  second  electrode  are  to  the  right  of  the  figure. 

potential  (that  is,  difference  in  amount  of  positive  or  negative  elec- 
tricity) between  the  two  parts  of  the  muscle  thus  led  off,  there  will 
be  a  swing  of  the  galvanometer  needle ;  the  galvanometer  detects  the 
existence  and  direction  of  any  current  that  occurs. 


120 


THE   ELECTRICAL   PHENOMENA   OF   MUSCLE 


[CH.  XL 


Fig.  137  shows  a  more  convenient  form  of  non-polarisable  elec- 
trodes. 

In  order  to  measure  the  strength  (elec- 
tromotive force)  of  such  currents,  the  mere 
amount  of  swing  of  the  needle  is  only  a  very 
rough  indication,  and  in  accurate  work  the 
arrangement  shown  in  fig.  138  must  be  used. 
The  electromotive  force  is  usually  measured 
in  terms  of  a  standard  Daniell  cell.  The 
two  surfaces  of  the  muscle  (M)  are  led  off 
to  a  galvanometer  (B) ;  the  needle  swings, 
and  then  a  fraction  of  a  Daniell  cell  is  intro- 
duced in  the  reverse  direction  so  as  to  neu- 
tralise the  muscle  current,  and  bring  back 
the  needle  to  rest.  From  the  Daniell  cell  K, 
wires  pass  to  the  ends  a,  b  of  a  long  platinum 
wire  of  high  resistance,  called  the  compen- 
sator ;  c  is  a  slider  on  this  wire  ;  a  and  c  are 
connected  to  the  galvanometer,  the  com- 

FIG.  iSS.-Arrangement  for  measuring  the  elec-     mutatpr  C  enabling  the  observer  to  ensure 
tromotive  force  of  muscle.  that  the  current  from  the  Daniell  passes  in 

the  opposite  direction  to  that  produced  by 

the  muscle.     If  the  slider  c  is  placed  at  the  end  b  of  the  compensator,  the  whole 
strength  of  the  Daniell  will  be  sen»t  through  the  galvanometer  and  will  more  than 


/too 


FIG.  139. — Lippmann's  Capillary  Electrometer.    (After  Waller.) 

1.  Pressure  apparatus  and  microscope  on  stand  of  which  the  capillary  tube  is  fixed. 

2.  Capillary  tube,  fixed  in  outer  tube  containing  10  per  cent,  sulphuric  acid  ;  the  platinuin 

wires  are  also  shown. 
|J.  Capillary  and  column  of  mercury  as  seen  in  the  field  of  the  microscopy. 


CH.  XI.]  THE   ELECTROMETER  121 

neutralise  the  muscle  current ;  if  c  is  half  way  between  a  and  />,  half  the  Darnell's 
strength  will  be  sent  in  ;  but  this  is  also  too  much  ;  ac  will  be  found  to  be  only 
quite  a  small  fraction  of  ab  •  and  this  fraction  will  correspond  to  a  proportional 
fraction  of  the  electromotive  force  of  the  Daniell  cell. 

Lippmann's  Capillary  Electrometer. — This  instrument  is  often  used  instead 
of  the  galvanometer.  It  consists  of  a  glass  tube  drawn  out  at  one  end  to  a  fine 
capillary  and  filled  with  mercury.  It  is  connected  to  an  apparatus  by  which  the 
pressure  on  this  mercury  can  be  lowered  or  increased.  The  open  capillary  tube  is 
enclosed  within  another  tube  filled  with  10  per  cent,  sulphuric  acid.  Two  platinum 
wires  fused  through  the  glass,  pass  respectively  into  the  mercury  and  the  acid,  and 
the  other  ends  of  these  wires  are  connected  by  electrodes  to  two  portions  of  the 
surface  of  a  muscle.  The  capillary  tube  is  observed  by  a  microscope  (see  fig.  139). 
The  surface  of  the  mercury  is  in  a  state  of  tension  which  is  easily  increased  or 
diminished  by  variations  of  electrical  potential,  and  the  mercury  moves  in  the 
direction  of  the  negative  pole. 

If  the  shadow  of  the  mercurial  column  is  thrown  upon  a  travelling  sensitive 
photographic  plate,  photographs  are  obtained  which  show  the  electrical  variations 
in  a  living  tissue  in  a  graphic  manner.  The  instrument  is  exceedingly  sensitive, 
and  its  indications  are  practically  instantaneous.  The  instrument  has  been  much 
used  in  investigating  the  electrical  changes  of  the  heart,  as  will  be  more  fully 
discussed  when  we  are  considering  that  organ. 

The  String  Galvanometer. — This  is  even  more  sensitive  than  the  capillary 
electrometer,  and  we  owe  its  introduction  to  Professor  Einthoven  of  Leiden.  In 
the  ordinary  galvanometer,  as  we  have  seen,  the  current  passes  through  a  fixed 
coil  of  wire,  and  deflects  a  small  magnet  suspended  in  the  centre.  This  arrange- 
ment can  be  inverted,  the  magnet  being  made  large  and  fixed  and  the  coil  small 
and  movable.  The  Einthoven  galvanometer  is  a  development  of  this  type.  The 
magnet  is  large,  and  shaped  so  as  to  give  a  very  intense  field,  and  the  "coil"  is 
reduced  to  a  single  thread  of  quartz,  silvered  on  the  surface  so  as  to  conduct  the 
current.  The  movements  of  this  thread  are  too  small  to  be  followed  by  the 
unaided  eye,  so  the  poles  of  the  magnet  are  pierced  by  a  hole  in  which  a  microscope 
magnifying  600  diameters  is  arranged,  so  as  to  cast  the  image  of  the  string  on  a 
moving  photographic  plate.  We  have  already  seen  one  use  of  this  instrument  in 
the  study  of  voluntary  muscular  contraction  (see  p.  106) ;  we  shall  have  to  return 
to  it  in  our  study  of  the  heart,  and  respiration,  in  later  chapters. 

We  can  now  pass  on  to  a  consideration  of  results. 

In  muscles  that  are  removed  from  the  body,  it  is  found  that  on 
leading  off  two  parts  of  their  surface  to  a  galvanometer,  the  galvan- 
ometer needle  generally  swings.  The  most  marked  result  is  obtained 
with  a  piece  of  muscle  in  which  the  fibres  run  parallel  to  one  another, 
and  the  longitudinal  surface  is  connected  with  one  of  the  cut  ends 
by  a  wire  (2  in  fig.  140). 

On  the  course  of  jhe  wire  a  galvanometer  indicates  that  a  current 
flows  from  the  centre  to  the  cut  end  outside  the  muscle,  and  from 
the  cut  end  to  the  centre  inside  the  muscle.  If,  now,  the  muscle  is 
thrown  into  tetanic  contraction,  the  needle  returns  more  or  less 
completely  to  the  position  of  rest. 

Du  Bois  Keymond,  who  first  described  these  facts,  called  the  first 
current  the  current  of  rest,  and  the  second  current  the  current  of 
action;  the  change  in  direction  is  indicated  by  the  expression 
negative  variation ;  this  means  that  the  current  of  action  is  in  the 
opposite  direction  to  the  current  of  rest,  and  therefore  lessens  or 
neutralises  it.  The  word  negative  is  therefore  used  in  its  arithmetical, 


122 


THE    ELECTRICAL   PHENOMENA    Gf   MUSCLE 


[CII.  XL 


not  its  electrical  sense.     Du  Bois  Beymond  explained  this  by  sup- 
posing that  a  muscular  fibre  is  built  up  of  molecules,  each  of  which 


FIG.  140. — Diagram  of  the  currents  in  a  muscle  prism.    (Du  Bois  Reymond.) 


is  galvanometrically  positive  in  the  centre  and  galvanometrically 
negative  at  both  ends.  So  when  a  muscle  is  cut  across,  a  number 
of  the  galvanometrically  negative  ends  of  these  molecules  is  exposed. 
On  contraction  the  difference  between  the  centre  and  ends  of  each 
molecule  is  lessened,  and  the  resultant  effect  on  the  whole  muscle 
(made  up  of  such  molecules)  is  similar. 

In  the  foregoing  sentence  I  have  employed  the  rather  cumbrous  adjectives, 
yalvanometrically  positive  and  galvanometrically  negative,  instead  of  the  terms 
positive  and  negative  which  are  usually  employed  by  physiologists. 

If  we  take  a  Daniell  cell  and  connect  it  to  a  galvanometer,  the  zinc,  as  we  have 
seen,  is  the  electro-positive  element,  and  the  copper  the  electro-negative  element, 
but  the  ends  of  the  wires  which  connect  these  metals  to  the  galvanometer  have  the 
reverse  names  ;  the  kathode  or  negative  pole  is  connected  to  the  zinc  or  positive 
metal ;  the  anode  or  positive  pole  is  connected  to  the  copper  or  negative  metal. 
The  current  enters  the  galvanometer  by  the  anode,  and  leaves  it  on  its  way 
back  to  the  zinc  by  the  kathode.  Therefore,  although  the  copper  is  electro- 
negative, it  may  be  spoken  of  as  galvanometrically  positive,  and  the  zinc  though 
electro-positive,  as  galvanometrically  negative. 

If  we  apply  this  to  a  muscle,  we  have  seen  that  the  current  flows  (in  the  wire 
that  connects  the  uninjured  longitudinal  surface  to  the  cut  end)  from  the  longi- 
tudinal surface  to  the  cut  end ;  the  longitudinal  surface  thus  corresponds  to  the 
copper  of  the  Daniell  cell,  and  is  therefore  electro-negative,  though  galvanometrically 
positive  ;  similarly  the  cut  end  corresponds  to  the  zinc,  and  is  electro-positive  though 
galvanometrically  negative. 

The  omission  of  the  qualifying  prefix  to  positive  and  negative  has  led  to  a  good 
deal  of  confusion  in  physiological  writings.  A  physicist  uses  the  terms  positive  and 
negative  as  meaning  electro-positive  and  electro-negative  respectively,  and  as  Dr 
Waller  has  pointed  out,  it  is  time  that  physiologists  adopted  the  same  nomenclature. 
In  what  now  follows,  I  propose  to  adopt  Dr  Waller's  suggestion. 

There  is  no  doubt  about  the  facts  as  described  by  Du  Bois 
Eeymond.  We  now  adopt,  however,  an  entirely  different  view  of 
their  meaning :  in  causing  this  revolution  of  ideas  the  principal  part 
has  been  played  by  Hermann.  Hermann  showed  that  the  so-called 


CH.  XL]  THE   DIPHASIC   VARIATION  123 

current  of  rest  docs  not  exist;  it  is  really  a  current  produced  by 
injury,  and  is  now  generally  called  a  demarcation  current :  the  more 
the  ends  of  the  muscle  are  injured  the  more  positive  they  become ; 
and  when  they  are  connected  to  the  uninjured  centre,  a  current 
naturally  is  set  up  as  described  by  Du  Bois  Ueyrnond.  If  a  muscle 
is  at  rest  and  absolutely  uninjured  it  is  iso-electric ;  that  is,  it  gives 
no  current  at  all  when  two  parts  of  it  are  connected  together  by  a 
wire. 

Since  Du  Bois  Keymond's  researches,  the  electrical  changes 
which  occur  during  a  single  twitch  have  been  studied,  also,  and 
before  we  can  understand  the  "  negative  variation "  of  tetanus,  it  is 
obviously  necessary  to  consider  the  electrical  variation  which  takes 
place  during  a  twitch,  for  tetanus  is  made  up  of  a  fused  series  of 
twitches. 

The  electrical  change  during  a  twitch  is  called  a  diphasic 
variation.  The  contracting  part  of  a  muscle  becomes  first  more 
positive  than  it  was  before ;  it  then  rapidly  returns  to  its  previous 
condition.  The  increase  of  positivity  indicates  a  disturbance  of 
the  stability  of  the  tissue ;  the  disappearance  of  this  increased 
positivity  is  the  result  of  a  return  of  the  muscular  tissue  to  a  state  of 
rest.  If  the  muscle  is  stimulated  at  one  end,  a  wave  of  contraction 
travels  along  it  to  the  other  end.  This  muscle-wave  (see  p.  100)  may 
be  most  readily  studied  in  a  curarised  muscle,  that  is,  in  a  muscle 
which  is  physiologically 
nerveless.  The  electrical 
variation  travels  at  the 
same  rate  as  the  visible 
contraction,  but  precedes  it. 

Suppose  two  points  (p 
and  d)  of  the  muscle  (fig. 
141)  are  connected  by  non- 
polarisable  electrodes  to  a 
galvanometer,  and  that  the 
muscle-wave  is  started  by  a 
single  stimulus  applied  at 

A ;    as    soon    as   the    wave  FlG  141 

reaches  p  this  point  be- 
comes positive  to  d,  and  therefore  a  current  flows  from  d  to  p 
through  the  galvanometer  G.  A  moment  later  the  two  points 
are  equi-potential  and  no  current  flows;  a  minute  fraction  of  a 
second*  later  this  balance  is  upset,  for  when  the  wave  reaches  the 
point  d,  that  point  is  positive  to  p,  and  the  galvanometer  needle 
moves  in  the  opposite  direction. 

*  The  time  will  vary  with  the  distance  between  p  and  d. 


124 


THE   ELECTRICAL   PHENOMENA   OF   MUSCLE 


[CH.  XI. 


The  galvanometer  is  not  the  best  instrument  to  employ  to 
demonstrate  these  facts ;  the  inertia  of  the  needle  may  be  so  great 
that  it  is  impossible  for  it  to  catch  and  respond  to  the  two  phases. 
Wedenski  has  made  extensive  use  of  the  telephone  instead,  and  the 


FIG.  142. — Diphasic  curve  (black)  of  the  normal  sartorius.  The  grey  curve  is  the  monophasic  curve  of 
the  same  muscle  when  one  electrometer  contact  was  placed  on  the  injured  end.  The  two  photo- 
graphic curves  are  placed  one  over  the  other  so  that  the  beginnings  coincide.  (Burdon  Sanderson.) 

sounds  produced  in  it  by  the  electrical  changes  in  the  muscle  are 
distinctly  audible.  An  appeal  to  the  eye,  however,  is  generally 
regarded  as  more  satisfactory  than  one  to  the  ear,  and  for  this  purpose 
the  capillary  electrometer  is  the  instrument  most  frequently  em- 
ployed, as  its  responses  are  immediate ;  the  mercury  moves  first  in 
one  direction,  and  then  in  the  other.  The  deep  black  curve  in  the 
next  figure  (fig.  142)  shows  the  record  obtaining  by  photographing 
the  movement  of  the  column  of  mercury  on  a  rapidly  travelling 
photographic  plate. 

The  capillary  electrometer  has  the  advantage  of  giving  us  the  means  of  measur- 
ing the  time  of  onset  and  duration  of  the  electrical  disturbance,  and  experiments 

made  with  this  instrument 
show  that  the  change  only 
lasts  a  few  thousandths  o*f 
a  second,  and  is  over  long 
before  the  other  changes 
in  form,  etc.,  are  com- 
pleted. Sir  J.  Burdon 
Sanderson  gives  the  follow- 
ing numbers  from  experi- 
ments with  the  frog's 
gastrocnemius.  When  the 
muscle  was  excited  through 
its  nerve  the  electrical 
response  began  T7%7  and 
the  change  of  form  T-£$^ 

FIG.  143.  second  after  the  stimula- 

tion ;  the  second  phase  of 

the  electrical  response  began  r$fo  second  after  excitation.  When  the  muscle  was 
directly  excited,  the  latent  period  was  much  shorter,  the  change  in  form  beginning 
T/w  and  the  electrical  change  in  less  than  Ttnrsy  second  after  excitation. 

If,  however,  instead  of  examining  the  electrical  change  in    the 
muscle  in  the  manner  depicted  in  fig.  141,  one  electrode  is  placed  on 


CH.  XI.] 


THE   ELECTROMETER   RECORD 


125 


the  uninjured  surface  and  the  other  on  the  cut  end  (see  fig.  143),  the 
electrical  response  is  a  different  one. 

Under  these  circumstances,  the  electrical  change  is  a  monophasic 
variation,  for  when  the  muscle-wave  reaches  d,  this  part  of  the 
muscle,  owing  to  its  injured  state,  does  not  respond  to  the 
excitatory  condition,  and  the  electrical  re- 
sponse is  also  extinguished. 

The  grey  curve  in  figs.  142  and  144  is  the 
graphic  record  of  the  change  as  revealed  by 
the  capillary  electrometer.  It  will  be  seen 
that  the  ascending  limb  of  the  curve  is  iden- 
tical in  the  two  cases,  but  that  the  second 
phase  is  absent.  From  the  point  at  which  the 
diphasic  curve  approaches  its  culmination  the 
injury  curve  diverges  from  it,  continuing  to 
ascend;  the  line  soon  after  becomes  hori- 
zontal, and  then  begins  slowly  to  decline. 
This  long  tail  denotes  only  the  gradual  dis- 
appearance of  polarisation  of  the  mercury 
meniscus. 

The  meaning  of  such  photographic  records  be- 
comes clear  by  testing  the  electrometer  with  known 
differences  of  potential,  and  from  such  data  it  is 
possible  to  construct  what  may  be  called  an  interpre- 
tation diagram  (fig.  144).  The  horizontal  line  is  that 
of  equipotentiality  of  the  two  surfaces  of  contact  p 
and  d.  The  curve  P'  expresses  the  relative  positivity 
of  the  surface  p ;  the  curve  D',  the  corresponding 
relative  positivity  of  the  surface  d.  S'  is  a  curve 
of  which  the  ordinates  are  the  algebraic  sums  of  the 
corresponding  ordinates  of  P'  and  D'.  S  is  the 
photographic  curve  which  expresses  S' ;  P  is  the 
photographic  curve  which  expresses  P'  (monophasic 
variation).  The  numbers  under  the  horizontal  line 
indicate  hundredths  of  a  second ;  the  distance  t  t' 
expresses  the  time  taken  by  the  wave  in  its  progress 
from  p  to  d. 

From  these  considerations  we  can  now  pass  to  study  what  occurs 
when  the  muscle  enters  into  tetanus.  The  simplest  case  is  that  which 
was  first  observed  by  Du  Bois  Eeymond.  He  placed  his  non- 
polarisable  electrodes  in  the  positions  indicated  in  fig.  143,  one  (p) 
on  the  comparatively  uninjured  surface,  the  other  (d)  on  the  devital- 
ised cut  end.  He  sent  in  the  tetanising  series  of  shocks  at  A.  The 
electrical  response  is  under  these  circumstances  a  summation  of  the 
individual  electrical  responses  evoked  by  instantaneous  stimuli ;  and 
the  monophasic  character  of  the  single  response  explains  easily  what 
occurs  during  tetanus ;  the  centre  of  the  muscle  becomes  more 
positive  than  it  was  before,  and  so  the  electrical  difference  of  potential 


FIG.  144.— Interpretation  dia- 
gram .    (Burden  Sanderson . ) 


126  THE   ELECTRICAL   PHENOMENA   OF   MUSCLE  [CH.  XI. 

between  the  centre  and  the  injured  end  is  lessened.  But  with  regard 
to  uninjured  muscle  the  problem  is  not  so  easy.  It  is  at  first  sight 
difficult  to  see  why  the  summed  effects  of  a  series  of  diphasic  varia- 
tions should  take  the  direction  of  the  first  phase,  as  was  found  to  be 
the  case  by  Du  Bois  Eeymond  in  experiments  with  the  frog's  gastroc- 
nernius.  One  would  have  anticipated  that  "negative"  variation  in 
the  arithmetical  sense  would  be  absent  altogether,  and  this  is  the  case 
in  absolutely  normal  muscles;  Hermann  has  shown  that  it  is  so 
during  tetanus  of  the  human  forearm.  But  a  muscle  removed  from 
an  animal's  body  cannot  be  considered  absolutely  normal,  and  if  the 
two  contacts  be  placed  on  the  comparatively  uninjured  longitudinal 
surface,  as  in  fig.  142,  a  negative  variation  is  observed,  each  excitatory 
phase  becoming  weaker  as  it  progresses,  and  the  second  phase  of 
each  diphasic  effect  is  weaker  than  the  first.  The  following  figure 
(fig.  145)  illustrates  the  record  obtained  by  the  capillary  electrometer 


FIG.  145. — Electrometer  record  of  injured  sartorius  during  tetanus.    (Burdon  Sanderson.) 

from  an  injured  sartorius  excited  14  times  a  second ;  each  oscillation 
represents  a  single  monophasic  variation.  The  individual  oscillations 
can,  however,  be  seen  when  the  excitations  follow  one  another 
more  rapidly,  even  up  to  80  or  100  per  second. 

Muscle  is  not  the  only  tissue  which  exhibits  electrical  phenomena. 
A  nerve  which  is  uninjured  is  iso-electric ;  injury  causes  a  demar- 
cation current ;  activity  is  accompanied  with  a  similar  diphasic  wave 
travelling  along  the  nerve  simultaneously  with  the  nervous  impulse. 
The  activity  of  secreting  glands,  vegetable  tissues,  retina,  etc.,  is 
accompanied  with  somewhat  similar  electrical  changes,  which  we 
shall  study  in  detail  later. 

But  the  most  prominent  exhibition  of  animal  electricity  is  seen 
in  the  electric  organs  of  electric  fishes.  In  some  of  these  fishes  the 
electric  organ  is  modified  muscle,  in  which  a  series,  as  it  were,  of 
hypertrophied  end-plates  correspond  to  the  plates  in  a  voltaic  pile. 


Cll.  XI.] 


THE   RHEOSCOPIC    FROG 


127 


In  other  fishes  the  electric  organ  is  composed  of  modified  skin  glands. 
But  in  each  case  the  electric  discharge  is  the  principal  phenomenon 
that  accompanies  activity. 


The  Rheoscopic  Prog. 

The  electrical  changes  in  muscle  can  be  detected  not  only  by 
the  galvanometer  and  electrometer,  but  also  by  what  is  known  as 
the  physiological  rheoscope ;  this  consists  of  an  ordinary  muscle-nerve 
preparation  from  a  fresh  and  vigorous  frog.  The  nerve  is  stimulated 
by  the  electrical  changes  occurring  in  muscles,  and  the  nervous 
impulse  so  generated  causes  a  contraction  of  the  muscles  of  the  rheo- 
scopic  preparation.  The  following  are  the  principal  experiments  that 
can  be  shown  in  this  way : — 

1.  Contraction  without  metals.  If  the  nerve  of  a  nerve-muscle 
preparation  A  is  dropped  upon  another  muscle  B  (fig.  146)  or  upon 


FIG.  146. — Galvani's  experiment  without  metals. 

its  own  muscle,  it  will  be  stimulated  by  the  injury  current  of  the 
muscle  on  which  it  is  dropped,  and  this  leads  to  a  contraction  of  the 
muscle  (A)  which  it  supplies.  The  experiment  succeeds  best  if  the 
nerve  is  dropped  across  a  longitudinal  surface  and  a  freshly  made 
transverse  section. 

2.  Secondary    contraction.     This   is    caused    by   the    current    of 


FIG.  147. — Secondary  contraction.    (After  Waller.) 

action.  If,  while  the  nerre  of  A  is  resting  on  the  muscle  B  (fig. 
147),  the  latter  is  made  to  contract  by  the  stimulation  of  its 
nerve,  the  nerve  of  A  is  stimulated  by  the  electrical  variation 
which  accompanies  the  contraction  of  the  muscle  B,  and  so  a  con- 
traction of  muscle  A  is  produced.  This  is  called  secondary  con- 


128  THE    ELECTRICAL   PHENOMENA   OF   MUSCLE  [CH.  XI. 

traction.  It  may  be  either  a  secondary  twitch  or  secondary  tetanus, 
according  as  to  whether  the  muscle  B  is  made  to  contract  singly  or 
tetanically. 

3.  Secondary  contraction  from  the  heart.  If  an  excised  but  still 
beating  frog's  heart  is  used  instead  of  muscle  B,  and  the  nerve  of 
A  laid  across  it,  each  heart's  beat,  accompanied  as  it  is  by  an  electrical 
variation,  will  stimulate  the  nerve  and  cause  a  twitch  in  the  rheo- 
scopic  muscle  A. 


CHAPTEE  XII 

THERMAL  AND  CHEMICAL  CHANGES  IN  MUSCLE 

IN  muscular  contraction  there  is  a  transformation  of  the  potential 
energy  of  chemical  affinity  into  other  forms  of  energy,  especially 
molar  motion  and  heat.  Heat  is  a  form  of  motion  in  which  there  is 
movement  of  molecules;  in  molar  motion  there  is  movement  of 
masses.  The  fact  that  when  a  blacksmith  hammers  a  piece  of  iron 
it  becomes  hot  is  a  familiar  illustration  of  the  transformation  of  one 
mode  of  movement  into  the  other.  Heat  is  measured  in  heat-units  or 
calories.  One  calorie  is  the  energy  required  to  raise  the  temperature 
of  1  gramme  of  water  from  0°  to  1°  C. ;  and  this  in  terms  of  work  is 
equal  to  425*5  gramme-metres,  that  is,  the  energy  required  to  raise 
the  weight  of  425*5  grammes  to  the  height  of  1  metre. 

A  muscle  when  uncontracted  is  nevertheless  not  at  absolute  rest. 
We  have  already  seen  that  it  possesses  tonus  or  tone ;  it  also  possesses 
what  we  may  call  chemical  tone;  that  is,  chemical  changes  are 
occurring  in  it,  and  consequently  heat  is  being  produced.  But  when 
it  contracts,  the  liberation  of  energy  is  increased ;  work  is  done,  and 
more  heat  is  produced;  the  heat  produced  represents  more  of  the 
energy  than  the  work  done.  The  more  resistance  that  is  offered  to  a 
muscular  contraction,  the  more  is  the  work  done  relatively  increased 
and  the  heat  diminished.  The  amount  of  heat  produced  is  increased 
by  increasing  the  tension  of  the  muscle.  It  diminishes  as  fatigue 
comes  on.  On  increasing  the  strength  of  the  stimulus  the  amount 
of  heat  increases  faster,  proportionately,  than  the  work  performed. 

If  work  is  done  by  a  few  large  contractions,  more  heat  is  produced 
than  if  the  same  work  is  done  by  a  larger  number  of  smaller  contrac- 
tions; that  is,  more  chemical  decomposition  occurs,  and  fatigue 
ensues  more  rapidly  in  the  first  case.  This  fact  is  within  the  personal 
experience  of  everyone.  If  one  ascends  a  tower,  the  work  done  is 
the  raising  of  the  weight  of  one's  body  to  the  top  of  the  tower.  If 
the  staircase  in  the  tower  has  a  gentle  slope,  each  step  being  low, 
far  less  fatigue  is  experienced  than  if  one  ascended  to  the  same  height 
by  a  smaller  number  of  steeper  steps. 

129 


130  THEKMAL   AND    CHEMICAL   CHANGES    IN   MUSCLE          [CH.  XII. 

On  a  cold  day  one  keeps  oneself  warm  by  muscular  exercise ;  this 
common  fact  is  confirmed  by  more  accurate  experiments  on  isolated 
muscles,  the  heat  produced  being  sufficient  to  raise  temporarily  the 
temperature  of  the  muscle.  This  can  be  shown  in  large  animals  by  in- 
serting a  thermometer  between  the  thigh  muscles  and  stimulating  the 
spinal  cord.  The  rise  of  temperature  may  amount  to  several  degrees. 

In  the  case  of  frog's  muscles,  Helmholtz  found  that,  after  tetanis- 
ing  them  for  two  or  three  minutes,  the  temperature  rises  014°  to 
018°  C. ;  and  for  each  single  twitch  Heidenhain  gives  a  rise  of 
temperature  of  from  O'OOl0  to  0'005°  C. 

For  the  detection  of  such  small  rises  in  temperature,  a  thermopile, 
and  not  a  thermometer,  is  employed. 

A  thermopile  consists  of  a  junction  of  two  different  metals;  the 
metals  are  connected  by  wires  to  a  galvanometer.  If  the  junction 
is  heated  an  electrical  current  passes  round  the  circuit,  and  is 
detected  by  the  galvanometer.  The  metals  usually  employed  are 


A<-B  D-A 

7  Couple.  2  Couples.  3  Couples, 

FIG. 148.  FIG. 149.  FIG. 150. 

FIGS.  148-150.— Scheme  of  thermo-electric  couples.    (After  Waller.) 

iron  and  German  silver,  or  antimony  and  bismuth.  If  the  number 
of  couples  in  the  circuit  is  increased,  each  is  affected  in  the  same 
way,  and  thus  the  electrical  current  is  increased  through  the  galvan- 
ometer. The  arrangement  is  shown  in  the  fig.  148,  which  also  indicates 
the  direction  of  the  currents  produced,  the  metals  employed  being 
antimony  and  bismuth.  By  using  16  couples  of  this  kind  Helmholtz 
was  able  to  detect  a  change  of  40100  of  a  degree  Centigrade. 

Within  certain  limits,  the  strength  of  the  current  is  directly 
proportional  to  the  rise  of  temperature  at  the  junction. 

If  two  couples  are  in  circuit,  as  shown  in  fig.  149,  and  they  are 
heated  equally,  no  current  will  pass  through  the  galvanometer, 
the  current  through  one  couple  being  opposed  by  the  current 
through  the  other.  But  if  the  two  couples  are  heated  unequally,  the 
direction  of  swing  of  the  galvanometer  needle  indicates  which  is 
the  warmer.  To  apply  this  to  the  frog's  gastrocnemius,  plunge  several 
needle-shaped  couples  (fig.  150)  into  a  frog's  gastrocnemius  of  one 
side  and.  the  same  number  of  couples  into  the  gastrocnemius  of  the 
other  side,  and  then  excite  first  one  then  the  other  sciatic  nerve ; 
a  deflection  of  the  galvanometer  will  be  observed  first  in  one,  then  in 
the  other  direction,  indicating  the  production  of  heat  first  on  one 
side,  then  on  the  other. 


CH,  XII.]  CHEMICAL  CHANGES   IN  MUSCLES  131 

Chemical  Changes  in  Muscles. 

The  chemical  changes  which  are  normally  occurring  in  a  resting 
muscle  are  much  increased  when  it  contracts.  Waste  products  of 
oxidation  are  discharged,  and  the  most  abundant  of  these  is  carbonic 
acid.  Sarcolactic  acid  is  also  produced,  and  the  alkaline  reaction  of 
a  normal  muscle  is  replaced  by  an  acid  one.  The  muscles  of  animals 
hunted  to  death  are  acid  ;  the  acid  reaction  to  litmus  paper  of  a  frog's 
gastrocnemius  can  be  readily  shown  after  it  has  been  tetanised  for  10 
to  15  minutes. 

When  a  muscle  contracts,  the  quantity  of  oxygen  consumed  is 
increased,  and  the  discharge  of  carbonic  acid  is  increased  also.  This 
is  the  cause  of  the  rise  in  heat-production  just  described.  It  is 
important  to  note,  however,  that  this  change  follows  rather  than 
accompanies  the  increase  of  work,  as  we  shall  see  more  at  length 
when  we  are  studying  tissue-respiration  (p.  397). 

For  a  certain  time  after  its  removal  from  the  body,  an  excised 
muscle  can  be  made  to  contract  and  give  off  oxidation  products  such 
as  carbonic  acid  in  an  atmosphere  containing  no  oxygen  at  all.  The 
oxygen  used  has  thus  been  stored  up  in  the  muscle  previously.  The 
oxygen  is  not,  however,  present  in  the  _  free  state,  for  no  oxygen  can 
be  detected  in  the  gases  obtained  from  muscles  by  means  of  an  air- 
pump.  Excised  muscles,  however,  must  be  regarded  as  partially 
asphyxiated,  for  their  individual  fibres  are  largely  cut  off  from  that 
ready  supply  of  oxygen  which  normally  reaches  them  by  the  blood. 
During  life  (and  the  living  condition  can  be  imitated  by  placing  an 
excised  muscle  in  an  atmosphere  of  pure  oxygen)  the  muscular 
substance  breaks  down  into  a  number  of  simpler  substances ;  one 
of  these  is  carbonic  acid.  The  others,  however,  or  some  of  them, 
are  at  once  built  up  again  with  the  inclusion  of  oxygen  and  some 
carbon-containing  substance,  perhaps  sugar,  into  living  material. 
The  muscle,  therefore,  does  not  contain  any  of  the  by-products  of 
its  own  metabolism.  In  excised  muscle,  when  the  oxygen  supply  is 
deficient  the  by  -  products  accumulate,  as  a  result  of  which  very 
striking  alterations  take  place : — (1)  The  reaction  of  the  muscle 
changes  and  the  phenomena  of  fatigue  and  functional  death  set  in. 
(2)  The  proteins  become  coagulated,  and  this  is  the  physical  basis  of 
rigor  mortis. 

There  are  other  chemical  changes  in  the  muscle  when  it  contracts, 
for  instance,  a  change  of  glycogen  into  sugar.  The  question  whether 
nitrogenous  waste  is  increased  during  muscular  activity  has  been  a 
much  debated  one.  It  has  now,  however,  been  finally  proved  that 
an  increased  consumption  of  carbon  (in  large  measure  derived  from 
the  carbohydrate  stored  in  the  muscle)  is  a  marked  and  immediate 
feature  of  muscular  activity.  Any  increase  in  the  consumption  of 


132  THERMAL  AND   CHEMICAL  CHANGES   IN   MUSCLE         [CH.  XII, 

nitrogen  is  negligible,  and  only  occurs  when  the  muscles  do  not 
receive  a  due  share  of  non-nitrogenous  food.  (See  more  fully  chapter 
on  Metabolism.) 

Fatigue. 

If  the  nerve  of  a  nerve-muscle  preparation  is  continually  stimu- 
lated, the  muscular  contractions  become  more  prolonged  (see  p.  97), 
smaller  in  extent,  and  finally  cease  altogether. 

The  muscle  is  said  to  be  fatigued :  this  is  due  to  the  consump- 
tion of  the  substances  available  for  the  supply  of  energy  in  the 
muscle,  but  more  particularly  to  the  accumulation  of  waste  pro- 
ducts of  contraction ;  of  these,  sarcolactic  acid  is  an  important  one. 
Fatigue  may  be  artificially  induced  in  a  muscle  by  feeding  it  on  a 
weak  solution  of  lactic  acid,  and  then  removed  by  washing  out  the 
muscle  with  salt  solution  containing  a  minute  trace  of  an  alkali.  If 
the  muscle  is  left  to  itself  in  the  body,  the  blood-stream  washes  away 
the  accumulation  of  acid  products,  and  fatigue  passes  off. 

The  question  next  presents  itself,  where  is  the  seat  of  fatigue  ? 
Is  it  in  the  nerve,  the  muscle,  or  the  end-plates  ?  If,  after  fatigue  has 
ensued  and  excitation  of  the  nerve  of  the  preparation  produces  no 
more  contractions,  the  muscle  is  itself  stimulated,  it  contracts ;  this 
shows  it  is  still  irritable,  and,  therefore,  not  to  any  great  extent  the 
seat  of  fatigue. 

If  an  animal  is  poisoned  with  curare,  and  it  is  kept  alive  by  arti- 
ficial respiration,  excitation  of  the  peripheral  end  of  a  motor  nerve 
produces  no  contraction  of  the  muscles  it  supplies.  If  one  goes  on 
stimulating  the  nerve  for  many  hours,  until  the  effect  of  the  curare  has 
disappeared,  the  block  at  the  end-plates  *  is  removed  and  the  muscles 
contract :  the  seat  of  exhaustion  is  therefore  not  in  the  nerves.  By 
a  process  of  exclusion  it  has  thus  been  localised  in  the  nerve-endings. 

When  the  muscle  is  fatigued  in  the  intact  body,  there  is,  however, 
another  factor  to  be  considered  beyond  the  mere  local  poisoning  of 
the  end-plates.  This  is  the  effect  of  the  products  .of  contraction 
passing  into  the  circulation  and  poisoning  the  central  nervous  system. 
This  aspect  of  the  question  has  been  specially  studied  by  Waller 
and  by  Mosso.  Mosso  devised  an  instrument  called  the  ergograph, 
which  is  a  modification  of  Waller's  dynamograph  invented  many 
years  previously.  The  arm,  hand,  and  all  the  fingers  but  one  are 
fixed  in  a  suitable  holder ;  the  free  finger  repeatedly  lifts  a  weight 
over  a  pulley,  and  the  height  to  which  it  is  raised  is  registered  by 
a  marker  on  a  blackened  surface. 

By  the  use  of  this  and  similar  instruments  it  has  been  shown 
that  the  state  of  the  brain  and  central  nervous  system  generally  is  a 

*  Another  convenient  block  which  is  sometimes  used  is  to  throw  a  constant 
current  into  the  nerve  between  the  point  of  excitation  and  the  muscles.  This  pre- 
vents the  nerve  impulses  from  reaching  the  muscles. 


CH.  XII.  ]  FATIGUE  133 

most  important  factor  in  fatigue,  and  that  the  fatigue  products  pro- 
duced in  the  muscles  during  work  cause  part  of  their  injurious 
effects  by  acting  on  the  central  nervous  system  and  diminishing  its 
power  of  sending  out  impulses. 

One  of  the  most  striking  of  Mosso's  experiments  illustrates  in  a 
very  forcible  manner  the  fact  that  the  central  nervous  system  is  more 
easily  fatigued  than  the  nerve-endings  in  muscle.  A  person  goes  on 
lifting  the  weight  until,  under  the  influence  of  the  will,  he  is  unable 
to  raise  it  any  more.  If  then  without  waiting  for  fatigue  to  pass  off, 
the  nerves  going  to  the  finger  muscles  are  stimulated  artificially  by 
induction  shocks,  they  once  more  enter  into  vigorous  contraction. 

Mosso  has  also  shown  that  the  introduction  of  the  blood  of  a 
fatigued  animal  into  the  circulation  of  a  normal  one  will  give  rise  in 
the  latter  to  all  the  symptoms  of  fatigue.  The  blood  of  the  fatigued 
animal  contains  the  products  of  activity  of  its  muscles,  but  still 
remains  alkaline ;  the  poisonous  substance  cannot  therefore  be  free 
lactic  acid.  Lactic  acid  is  doubtless  one  only  of  the  products  of 
muscular  activity;  we  have  at  present  no  accurate  knowledge  of 
the  chemical  nature  of  the  others. 

It  should,  however,  be  mentioned  that  some  physiologists  (Lee, 
loteyko,  etc.),  still  regard  the  effect  on  the  end  plates  as  the  most 
important  factor  in  fatigue. 

The  statement  that  nerves  are  not  fatiguable,  does  not  mean  that  the  nerve- 
fibres  undergo  no  metabolic  changes  when  transmitting  a  nerve  impulse,  but  that 
the  change  is  so  slight,  and  the  possibilities  of  repair  so  great,  that  fatigue  in  the 
usual  acceptation  of  the  term  cannot  be  demonstrated.  Waller  made  the  interesting 
but  tentative  suggestion  that  the  medullary  sheath  is  a  great  factor  in  repair,  or,  in 
his  own  words,  "  the  active  grey  axis  both  lays  down  and  uses  up  its  own  fatty 
sheath,  and  it  is  inexhaustible  not  because  there  is  little  or  no  expenditure,  but 
because  there  is  an  ample  re-supply." 

A  year  or  two  after  these  words  were  written,  Miss  Sowton,  at  Dr  Waller's 
suggestion,  undertook  a  piece  of  work  in  order  to  test  the  truth  of  this  hypothesis. 
If  the  absence  of  fatigue  is  due  to  the  presence  of  the  fatty  sheath,  fatigue  ought 
to  be  demonstrable  in  nerve-fibres  in  which  the  fatty  sheath  is  absent.  She 
selected  the  olfactory  nerve  of  the  pike  as  the  non-medullated  nerve  with  which  to 
try  the  experiment,  and  her  results  confirmed  Dr  Waller's  expectation  ;  the  galvano- 
metric  replies  of  the  nerve  became  somewhat  feebler  after  repeated  stimulation. 

It  appeared  to  me  advisable  to  test  the  question  in  another  way.  The  splenic 
nerves  seemed  to  be  the  most  convenient  large  bundles  of  non-medullated  fibres 
for  the  purpose.  Dr  T.  G.  Brodie  was  associated  with  me  in  carrying  out  the  in- 
vestigation. A  dog  is  anaesthetised,  the  abdomen  opened,  the  spleen  exposed,  and 
the  splenic  nerves  which  lie  by  the  side  of  the  main  splenic  artery  are  laid  bare. 
It  is  quite  easy  to  dissect  out  a  length  of  nerve  sufficient  for  the  experiment  (1^  to  2 
inches).  The  nerve  is  then  cut  as  far  from  the  spleen  as  possible,  and  the  spleen 
is  enclosed  in  an  air  oncometer  connected  to  the  bellows  volume  recorder  invented 
by  Dr  Brodie.  On  stimulating  the  nerve  with  a  weak  faradic  current  the  organ 
contracts,  and  the  recording  lever  falls.  The  diminution  of  the  size  of  the  spleen 
is  quite  visible  to  the  naked  eye,  however,  without  the  use  of  any  apparatus.  The 
next  thing  to  do  is  to  put  a  block  on  the  course  of  the  nerve,  which  will  prevent 
the  nerve  impulses  from  reaching  the  spleen.  Here  we  met  with  some  difficulty. 
Curare  and  atropine  are  both  ineffective:  the  constant  current  has  a  great  dis- 
advantage ;  non-medullated  nerves  are  so  much  affected  that  very  feeble  constant 


134 


THERMAL  AND  CHEMICAL  CHANGES  IN  MUSCLE    [CH.  XII. 


currents  will  completely  block  the  transmission  of  impulses,  and  not  only  that,  but 
the  nerve  remains  blocked  after  the  current  is  removed.  After  the  current  has 
been  allowed  to  flow  for  two  minutes  the  nerve  remains  impassable  to  nerve 
impulses  for  an  hour  or  more,  and  then  slowly  recovers.  If,  therefore,  faradic 
excitation  of  the  nerve  is  kept  up  all  this  time  and  fails  to  excite  the  contraction  of 
the  spleen  after  the  removal  of  the  constant  current,  it  is  impossible  to  say  whether 


G.P. 


S 


N 


Fio.  151. — Apparatus  for  obtaining  splenic  curves,  s,  Spleen  in  oncometer  o,  which  is  made  of  gutta 
percha,  and  covered  with  a  glass  plate  (G.P.)  luted  on  with  vaseline.  M  is  the  splenic  mesentery 
containing  vessels  and  nerves  ;  this  passes  through  a  slit  in  the  base  of  the  oncometer  which  is  made 
air-tight  with  vaseline.  The  oncometer  is  connected  to  the  flexible  bellows  (B)  by  the  india-rubber 
tube  (R),  the  side  tube  (T)  being  closed  during  an  experiment  by  a  piece  of  glass  rod.  The  recording 
lever  (L)  writes  on  a  revolving  drum. 

this  is  due  to  fatigue  of  the  nerve-fibres  on  the  proximal  side  of  the  block,  or  whether 

it  may  not  be  due  to  the  fact  that  the  block  (due  to  electrolytic  changes  caused 

constant  current)  is  still  effective. 

Our  best  results  were  obtained  by  using  cold  instead  of  a  constant  current  as 

our  blocking  agent. 

Fig.  151  is  an  outline  drawing  of  the  apparatus  used,  and  fig.  152  shows  the 

arrangement  adopted  in   connection  with   the    nerve. 

The  nerve  (N)  rests  on  a  metal  tube  (T)  through  which 
water  can  be  kept  flowing.  E  is  the  situation  of  the 
electrodes.  If  the  nerve  is  excited,  the  spleen  con- 
tracts, and  the  recording  lever  (in  fig.  151)  falls.  If 
now  brine  at  0  to  2°  C.  is  kept  flowing  through  T,  the 
nerve  impulses  are  blocked  by  the  cold,  and  cannot 
reach  the  spleen.  Immediately  the  cold  brine  is  re- 
placed by  warm  water  at  30°  C.,  the  nerve  again  becomes 
passable  by  nerve  impulses,  and  the  spleen  contracts 
once  more. 

While  the  fluid  in  T  is  kept  at  the  low  temperature 
mentioned,  the  nerve  is  excited  with  strong  induction 
shocks  all  the  time,  and  the  spleen  remains  irre- 
sponsive ;  the  nerve  impulses  are  able  to  reach  T  but 
not  to  pass  it.  If  then  warm  water  is  passed  through  T, 
and  the  block  produced  by  the  cold  is  thus  removed, 
and  the  spleen  continues  to  be  irresponsive,  we  have  a 
proof  that  the  piece  of  nerve  between  E  and  T  has  been 
fatigued.  But  our  experiments  have  shown  us  that 
non-medullated  nerve  is  just  as  difficult  to  fatigue  as 
medullated  nerve.  Even  after  six  hours'  continuous 


DT 


FIG.  152. — Arrangement  of  ap- 
paratus in  connection  with 
the  splenic  nerve,  s  is  the 
spleen,  and  N  the  main 
bundle  of  nerves.  The 
nerve  rests  on  the  metal 
tube  (T)  through  which  fluid 
at  the  required  temperature 
is  kept  flowing,  and  on  the 
electrodes  (E)  which  come 
from  the  secondary  coil  of 
an  inductorium. 


excitation  the  nerve  is  just  as  excitable  as  it  was  at  the  start,  and  a  full  splenic 
contraction  is  obtained  when  the  cold  block  is  removed. 


CH.  XII.]  FATIGUE   IN   NERVE  135 

We  have  made  similar  experiments  with  vaso-rnotor  nerves,  such  as  the  cervical 
sympathetic  nerve  in  the  rabbit,  the  splanchnic  nerve  of  the  dog,  and  the  sciatic 
nerve  in  a  curarised  dog,  and  have  obtained  corresponding  results.  This  confirms 
the  work  previously  published  by  Eve.  Eve  excited  the  cervical  sympathetic  for 
twelve  hours,  and  found  no  loss  of  excitability  at  the  end  of  that  time.  Eve 
stimulated  the  nerve  below  the  upper  cervical  ganglion,  and  the  main  object  of  his 
work  was  to  ascertain  whether  any  histological  evidence  of  fatigue  could  be  found 
in  the  cells  of  the  ganglion.  The  only  change  he  could  find  there  was  a  somewhat 
diffuse  staining  of  the  cells  by  methylene  blue,  which  he  attributes  to  the  formation 
of  acid  substances  in  the  cells.  A  blue  stain  of  similar  appearance  may  be  induced 
in  the  motor  cells  of  the  spinal  cord,  after  exhaustion  is  produced  in  them  by  giving 
strychnine.  In  such  experiments  the  spinal  cord  becomes,  as  a  rule,  distinctly  acid 
to  litmus  paper.  Max  Verworn  has  more  recently  employed  strychnine  as  a  means 
of  producing  fatigue.  He  considers  that  the  only  specific  effect  of  this  alkaloid  is 
increase  of  reflex  activity,  and  he  attributes  the  subsequent  paralysis  to  vascular 
conditions  and  the  accumulation  of  fatigue  products,  among  which  he  places  carbon 
dioxide  in  the  first  rank.  Eve,  on  the  contrary,  did  not  find  that  carbonic  acid 
alone  produces  the  effects. 

We  must  conclude  from  such  experiments  that  Dr  Waller's  theory  is  unproved, 
and  that  while  fatigue  is  demonstrable  in  nerve-cells,  it  cannot  be  shown  to  occur 
in  nerve-fibres  of  either  the  medullated  or  non-medullated  variety  by  these  methods. 

In  carrying  out  these  experiments  we  noticed  that  though  no  functional  fatigue 
can  be  demonstrated,  there  is  noticeable,  especially  in  vaso-motor  nerves,  a 
phenomenon  which  Howell  terms  stimulation  fatigue  ;  this  means  that  the  actual 
spot  of  nerve  stimulated  becomes  after  a  time  less  excitable,  and  finally,  inexcitable, 
though  it  will  still  transmit  impulses,  if  the  excitation  is  applied  above  the  spot 
originally  stimulated.  We  think  that  the  use  of  the  term  "fatigue"  in  this  con- 
nection is  a  mistake ;  the  prolonged  electrical  excitation  causes  injurious  polarisa- 
tion (due  to  electrolytic  changes)  of  the  nerve,  which  renders  it  less  excitable.  This 
view  has  been  confirmed  by  Prof.  Gotch  by  means  of  experiments  with  the  capillary 
electrometer.  This  so-called  *'  stimulation  fatigue "  was  not  excluded  in  Miss 
Sowton's  experiments,  and  will  possibly  explain  her  results.  The  splenic  nerves, 
curiously  enough,  do  not  exhibit  this  phenomenon  in  any  marked  degree,  and  so 
were  peculiarly  well  adapted  to  test  the  question  of  functional  fatigue.  On  a  priori 
grounds  we  should  hardly  expect  non-medullated  nerves  to  be  peculiarly  susceptible 
of  real  fatigue,  when  one  considers  that  many  of  them,  such  as  the  vaso-con- 
strictors,  are  in  constant  action  throughout  life. 

It  should  be  clearly  understood  that  all  these  experiments  prove  only  that 
nerve-fibres  are  not  fatiguable  under  ordinary  conditions  of  stimulation.  If  we 
assume  that  nerve  is  entirely  "unfatiguable,"  we  must  assume  also  that  its 
activity  is  not  associated  with  the  consumption  of  material  and  the  production  of 
waste  products.  This  would  render  nerve  unique  among  all  the  other  tissues  of  the 
body,  and  is,  moreover,  contradicted  by  recent  discoveries  of  evidence  of  metabolic 
changes  in  a  nerve  during  its  activity.  We  are  therefore  driven  to  the  conclusion 
that  repair  is  exceedingly  rapid  and  perfect,  although  it  is  impossible  to  agree  with 
Waller  that  the  repairing  process  is  definitely  associated  with  the  presence  of  a 
medullary  sheath.  The  interval  between  successive  induction  shocks  is  certainly 
short,  but  it  is  apparently  long  enough  to  allow  the  nerve  to  recover  completely 
before  the  next  stimulus  arrives.  If,  however,  the  interval  between  two  successive 
stimuli  is  made  very  brief  indeed  (O'OOG  sec.),  the  second  stimulus  is  ineffective 
because  of  the  fatigue  due  to  the  first.  If  the  irritability  of  the  nerve  is  depressed 
by  cold,  by  asphyxia,  or  by  an  anaesthetic  (such  as  yohimbine),  the  irresponsive 
period  may  be  lengthened  to  as  much  as  one  to  two  tenths  of  a  second. 

In  one  of  the  foregoing  paragraphs  the  following  sentence  occurs  :  "fatigue  is 
demonstrable  in  nerve-cells."  M'Dougall  has  recently  adduced  evidence  that 
fatigue  in  the  central  nervous  system  has  its  seat  not  so  much  in  the  bodies  of  the 
nerve-cells  as  in  their  synaptic  junctions,  which  are  the  points  of  highest  resistance 
(that  is,  where  impulses  pass  with  greatest  difficulty)  in  all  mental  and  other 
operations  in  which  the  brain  and  spinal  cord  share,  even  when  no  fatigue  exists. 


136  THERMAL   AND    CHEMICAL   CHANGES    IN    MUSCLE         [CH.  XII. 

Rigor  Mortis. 

After  death,  the  muscles  gradually  lose  their  irritability  and  pass 
into  a  contracted  condition.  This  affects  all  the  muscles  of  the  body, 
and  usually  fixes  it  in  the  natural  posture  of  equilibrium  or  rest. 
The  general  stiffening  thus  produced  constitutes  rigor  mortis  or  post- 
mortem rigidity. 

The  cause  of  rigor  is  the  coagulation  of  the  muscle-plasma,  which 
is  more  fully  described  in  the  next  section.  This  coagulation  results 
in  the  formation  of  myosin,  and  is  gradual  in  onset.  Simultaneously 
the  muscles  (a)  become  shortened  and  opaque,  (b)  heat  is  evolved,  (c) 
they  give  off  carbonic  acid,  and  (d)  become  acid  in  reaction ;  this  is  due 
in  part  to  the  formation  of  sarcolactic  acid,  and  in  part  to  the  forma- 
tion of  acid  phosphates. 

After  a  varying  interval,  the  rigor  passes  off,  and  the  muscles  are 
once  more  relaxed.  This  sometimes  occurs  too  quickly  to  be  caused 
by  putrefaction,  and  there  is  very  little  doubt  that  it  is  really  the 
first  stage  in  the  self-digestion  or  autolysis  which  occurs  in  all  tissues 
after  death,  owing  to  the  presence  of  intracellular  enzymes  or  fer- 
ments. It  is  known  that  a  pepsin-like  or  proteolytic  enzyme  is 
present  in  muscle,  as  in  many  other  animal  tissues,  kidney,  spleen, 
etc.  (Hedin),  and  that  such  enzymes  act  best  in  an  acid  medium. 
The  conditions  for  the  solution  of  the  coagulated  myosin  are  there- 
fore present,  as  the  reaction  of  rigored  muscle  is  acid. 

Order  of  Occurrence. — The  muscles  are  not  affected  simultaneously 
by  rigor  mortis.  It  affects  the  neck  and  lower  jaw  first ;  next,  the  upper 
extremities,  extending  from  above  downwards ;  and  lastly,  reaches  the 
lower  limbs ;  in  some  rare  instances  it  affects  the  lower  extremities 
before,  or  simultaneously  with,  the  upper  extremities.  It  usually 
ceases  in  the  order  in  which  it  begins :  first  at  the  head,  then  in  the 
upper  extremities,  and  lastly  in  the  lower  extremities.  It  seldom  com- 
mences earlier  than  ten  minutes,  or  later  than  seven  hours  after  death ; 
and  its  duration  is  greater  in  proportion  to  the  lateness  of  its  accession. 

The  occurrence  of  rigor  mortis  is  not  prevented  by  the  previous 
existence  of  paralysis  in  a  part,  provided  the  paralysis  has  not  been 
attended  with  very  imperfect  nutrition  of  the  muscular  tissue. 

In  some  cases  of  sudden  death  from  lightning,  violent  injuries,  or  paroxysms  of 
passion,  rigor  mortis  has  been  said  not  to  occur  at  all ;  but  this  is  not  always  the 
case.  It  may,  indeed,  be  doubted  whether  there  is  really  a  complete  absence  of 
the  post-mortem  rigidity  in  any  such  cases  ;  for  the  experiments  of  Brown-Sequard 
make  it  probable  that  the  rigidity  may  supervene  immediately  after  death,  and 
then  pass  away  with  such  rapidity  as  to  be  scarcely  observable. 

Chemical  Composition  of  Muscle. 

The  phenomena  of  rigor  mortis  will  be  more  intelligible  if  we 
consider  the  chemical  composition  of  muscle. 


CH.  XII.] 


CHEMICAL   COMPOSITION   OF   MUSCLE 


137 


The  connective  tissue  of  muscle  resembles  connective  tissue  else- 
where; the  gelatin  and  fat  obtained  in  analyses  of  muscle  are 
derived  from  this  tissue.  The  sarcolemma  is  composed  of  a  substance 
which  resembles  elastin  in  its  solubilities. 

The  contractile  substance  within  the  muscular  fibres  is,  during 
life,  of  semi-liquid  consistency,  and  contains  a  large  percentage  of 
proteins  and  smaller  quantities  of  extractives  and  inorganic  salts. 
By  the  use  of  a  press  this  substance  can  be  squeezed  out  of  perfectly 
fresh  muscles,  and  it  is  then  called  the  muscle-plasma. 

After  death,  muscle-plasma,  like  blood-plasma,  coagulates  (thus 
causing  the  stiffening  known  as  rigor  mortis).  The  solid  clot  corre- 
sponding to  the  fibrin  from  blood-plasma  is  called  myosin,  and  the 
liquid  residue  is  called  the  muscle-serum. 

Pursuing  the  analogy  further,  it  is  found  that  the  coagulation  of 
both  muscle-plasma  and  blood-plasma  can  be  prevented  by  cold,  by 
strong  solutions  of  neutral  salts,  and  by  potassium  oxalate,  which 
precipitates,  as  the  insoluble  oxalate  of  calcium,  the  lime  salts 
essential  for  the  coagulation  process.  In  both  cases  the  clotting  is 
produced  by  the  action  of  an  enzyme  developed  after  death.  In 
both  cases  the  precursor  of  the  solid  clot  is  a  protein  of  the  globulin 
class  which  previously  existed  in  solution. 

Fibrin  in  the  blood-clot  is  formed  from  the  previously  soluble 
fibrinogen  of  the  blood-plasma.  Myosin  in  the  muscle-clot  is  formed 
from  the  previously  soluble  myosinogen  *  of  the  muscle-plasma.  When 
the  blood-clot  contracts  it  squeezes  out  blood-serum;  when  the 
muscle-clot  contracts  it  squeezes  out  muscle-serum.  The  muscle- 
serum  contains  small  quantities  of  albuminous  material,  together  with 
the  extractives  and  salts  of  the  muscle.  The  origin  of  the  sarco- 
lactic  acid  is  a  controversial  question :  some  believe  it  originates  from 
the  carbohydrate  (glycogen  and  sugar) ;  others  think  it  comes  from 
the  protein  molecules  in  the  muscle. 

The  general  composition  of  muscular  tissue  is  the  following : — 

Water      .  .  .  75    per  cent. 

Solids 


Proteins  . 
Gelatin  . 
Fat 

Extractives 
Inorganic  salts 


18 
J2  to  5 

0-5 
1  to  2 


The  proteins,  as  already  stated,  chiefly  pass  into  the  clot :  very 
little  is  found  in  the  muscle-serum. 

The  extractives  comprise  a  large  number  of  organic  substances, 
all  present  in  small  quantities,  some  of  which  are  nitrogenous,  like 
creatine,  creatinine,  xanthine,  and  hypoxanthine :  the  rest  are  non- 
nitrogenous — namely,  fats,  glycogen,  sugar,  inosite,  and  the  variety 

*  For  further  details  see  small  text  at  the  end  of  this  chapter. 


138  THERMAL   AND    CHEMICAL   CHANGES    IN'  MUSCLE  [CI1.   XII. 

of  lactic  acid  known  as  sarcolactic  acid.  The  inorganic  salts  are 
chiefly  salts  of  potassium,  especially  potassium  phosphate. 

The  condition  of  dead  muscle  reminds  one  somewhat  of  contracted 
muscle.  Indeed,  the  similarity  is  so  striking  that  Hermann  pro- 
pounded the  idea  that  contracted  muscle  is  muscle  on  the  road  to 
death,  the  differences  between  the  two  being  of  degree  only.  He 
considers  that,  on  contraction,  a  hypothetical  material  termed  inogen 
is  broken  up  into  carbonic  acid,  sarcolactic  acid,  and  myosin;  on 
death  the  same  change  occurs,  only  to  a  much  more  marked  extent. 

This  idea  is  a  far-fetched  one,  but  it  is  a  useful  reminder  of  the 
similarities  of  the  two  cases.  In  chemical  condition,  contracted  and 
dead  muscle  are  alike,  so  far  as  the  formation  of  acid  products  is 
concerned;  there  is,  however,  no  evidence  of  any  formation  of  a 
muscle-clot  (myosin)  during  the  contraction  of  living  muscle,  as 
there  is  in  dead  muscle.  Then  heat  is  produced  in  both  cases, 
and  in  both  cases  also  the  muscle  is  electro-positive  to  uncontracted 
muscle. 

Here,  however,  the  analogy  must  end :  for  living  contracted 
muscle  is  irritable,  dead  muscle  is  not.  Living  contracted  muscle  is 
more  extensible  than  uncontracted  muscle ;  muscle  in  rigor  mortis  is 
not  so  (see  fig.  129,  p.  111).  The  contraction  of  living  muscle  is 
favoured  by  feeding  it  with  a  solution  of  dextrose,  while  the  process 
of  rigor  is  hindered  by  the  same  solution.  (F.  S.  Lee.) 

Our  correct  knowledge  of  the  proteins  of  muscle  and  of  the  phenomena  of  rigor 
mortis  date  from  the  year  1864,  when  Kiihne  obtained  muscle-plasma  by  subjecting 
frozen  frog's  muscle  to  strong  pressure.  A  good  many  years  later  I  was  successful 
in  repeating  these  experiments  with  mammalian  muscle.  By  fractional  heat  coagula- 
tion, and  by  their  varying  solubilities  in  neutral  salts,  I  was  able  to  separate  four 
different  proteins  in  the  muscle-plasma. 

1.  A  globulin  precipitable  by  heat  at  47°  C.     This   is   analogous  to  the  cell- 
globulin  found  in  most  protoplasmic  structures.     I  gave  it  the  name  paramyosinogen. 

2.  A  proteid  with  many  of  the  characters  of  a  globulin,  coagulable  by  heat  at 
56°  C.  ;    and  this  I  termed  myosinogen. 

3.  A  globulin  (myoglobulin),  precipitable  by  heat  at  63°  C. 

4.  An  albumin  similar  in  its  properties  to  serum  albumin  is  also  present ;  but 
this  and  the  myoglobulin  only  occur  in  quite  small  amounts. 

In  addition  to  these,  there  is  a  small  quantity  of  nucleo-protein  from  the  nuclei, 
and  in  the  red  muscles  haemoglobin  is  present ;  the  normal  pigment  of  the  so-called 
pale  muscles  is  termed  myohcematin  by  MacMunn,  and  this  is  doubtless  a  derivative 
of  haemoglobin. 

The  two  most  abundant  and  important  proteins  are  the  first  two  in  the  list, 
namely,  paramyosinogen  and  myosinogen.  They  occur  in  the  proportion  of  about 
1  to  4,  and  both  enter  into  the  formation  of  the  muscle-clot  (myosin).  The  myo- 
globulin is  probably  derived  from  the  adherent  connective  tissue  and  the  albumin 
from  adherent  blood  and  lymph. 

In  1895  v.  Fiirth  took  up  the  subject.  On  the  main  question  we  are  in  substantial 
agreement,  namely,  that  in  the  muscle-plasma  there  are  the  two  proteins  just  alluded 
to,  and  that  these  both  contribute  to  the  formation  of  the  muscle-clot.  The  main 
points  of  diiference  between  us  are  in  the  names  of  the  proteins.  He  uses  physio- 
logical saline  solution  to  extract  the  muscle-plasma,  and  this  extract  coagulates 
spontaneously  on  standing  ;  he  is  doubtful  whether  a  specific  myosin-ferment  brings 
about  the  change.  Paramyosinogen  he  terms  myosin,  and  this  passes  directly  into 


CH.  XII.] 


PROTEINS   OF  MUSCLE 


139 


the  clotted  condition  ;  but  myosinogcn,  called  myogen  by  v.  Fiirth,  first  passes  into 
a  soluble  condition  (coagulable  by  heat  at  the  remarkably  low  temperature  of 
40°  C.)  before  it  clots  :  the  soluble  stage  he  calls  soluble  mi/ oy en- fibrin  ;  a  better  name 
is  soluble  my  ox  in. 

We  may  put  this  in  a  diagrammatic  way  as  follows  : — 

Proteins  of  the  living  muscle. 


Paramyosinogen 


Myosinogen. 


Soluble  myosin. 


Myosin 
(the  protein  of  the  Muscle-clot). 

V.  Fiirth  also  calls  attention  to  some  characters  of  myosinogen  which  separate 
it  from  the  typical  globulins  ;  e.g.,  it  is  not  precipitable  by  dialysingthe  salts  away 
from  its  solutions.  It  may  be  therefore  called  an  atypical  globulin. 

In  mammalian  muscle,  soluble  myosin  is  only  found  as  a  stage  in  the  process 
of  rigor  mortis,  but  in  the  muscles  of  the  frog  and  other  amphibia  it  is  present 
as  such  in  the  living  muscle. 

The  muscle-plasma  from  fishes'  muscle  contains  another  protein  termed  myo~ 
protein  by  v.  Fiirth.  It  is  precipitable  by  dialysis,  but  not  coagulable  by  heat. 

Brodie,  and  later,  Vernon,  did  some  interesting  experiments  on  heat  rigor. 
When  a  muscle  is  heated  above  a  certain  temperature  it  becomes  contracted  and 
stiff,  losing  its  irritability  completely.  This  is  due  to  the  coagulation  of  the  muscle 
proteins.  If  a  tracing  is  taken  of  the  contraction,  it  is  found  to  occur  in  a  series  of 


muscle  is  used,  there  are  three  steps,  namely,  at  40°  (coagulation  temperature  of 
soluble  myosin),  47°,  and  56°.  This  work  of  Brodie's  is  especially  valuable  because 
it  teaches  us  that  the  proteins  in  muscle-plasma,  or  in  saline  extracts  of  muscle, 
are  present  also  in  the  actual  muscle-substance.  He  also  made  clear  another 
important  point,  namely,  that  the  irritability  of  the  muscle  is  lost  after  the  first 
step  in  the  shortening  has  occurred.  In  other  words,  in  order  to  destroy  the 
vitality  of  muscular  tissue,  it  is  not  necessary  to  raise  the  temperature  sufficiently 
high  to  coagulate  all  its  proteins,  but  that  when  one  of  the  muscular  proteins  has 
been  coagulated,  the  living  substance  as  such  is  destroyed ;  the  proteins  of  muscle 
cannot  therefore  be  regarded  as  independent  units;  the  unit  is  protoplasm,  and  if 
one  of  its  essential  constituents  is  destroyed,  protoplasm  as  such  ceases  to  live. 

Hans  Przibram  has  attempted  to  classify  the  Animal  kingdom  on  the  basis  of 
the  muscle-proteins ;  his  conclusions  are  based  on  the  examination  of  only  thirty 
species  of  animals,  ana  may  require  revision  in  the  future,  but  such  as  they  are,  they 
are  as  follows : — 

Invertebrates  :  paramyosinogen  present ;  myosinogen  absent. 

Vertebrates  :  paramyosinogen  and  myosinogen  both  present. 

Fishes  :  in  addition  to  these  two  principal  proteids,  soluble  myosin  and  myo- 
protein  (in  large  quantities)  occur. 

Amphibians  :  like  fishes,  except  that  myoprotein  is  only  present  in  traces. 

Reptiles,  birds,  mammals :  myoprotein  is  absent,  and  soluble  myosin  is  only 
present  when  rigor  mortis  commences. 


CHAPTEE  XIII 

COMPARISON   OF  VOLUNTARY  AND   INVOLUNTARY   MUSCLE 

THE  main  difference  between  voluntary  and  involuntary  muscle  is  the 
difference  expressed  in  their  names.  Voluntary  muscle  is  under  the 
control  of  that  portion  of  the  central  nervous  system  the  activity  of 
which  is  accompanied  by  volition.  Involuntary  muscle,  on  the  other 
hand,  is,  as  a  rule,  also  under  the  control  of  the  central  nervous 
system,  but  of  a  portion  of  the  central  nervous  system  the  activity 
of  which  is  independent  of  volition.  There  appear,  however,  to  be 
exceptions  to  this  rule,  and  the  involuntary  muscle  executes  its  con- 
tractions independently  of  nervous  control ;  that  is  to  say,  it  is 
sometimes  in  the  truest  sense  of  the  term  really  involuntary.  This 
is  very  markedly  seen  in  the  developing  heart  of  the  embryo,  which 
begins  to  beat  before  any  nerve-fibres  have  grown  into  it  from  the 
central  nervous  system. 

Another  characteristic  of  involuntary  muscle  is  a  tendency  to 
regular  alternate  periods  of  rest  and  activity,  or  rhythmicality.  This 
is  best  exemplified  in  the  heart,  but  it  is  also  seen  in  the  lymphatic 
vessels,  especially  the  lymph  hearts  of  the  frog,  and  the  mesenteric 
lymphatic  vessels  (lacteals)  of  many  animals.  It  is  seen  in  the 
veins  of  the  bat's  wing,  and  in  the  muscular  tissue  of  the  spleen, 
stomach,  intestine,  bladder,  and  other  parts. 

A  third  characteristic  of  involuntary  muscle  is  peristalsis.  If 
any  point  of  a  tube  of  smooth  muscle  such  as  the  small  intestine  is 
stimulated,  a  ring-like  constriction  is  produced  at  this  point.  After 
lasting  some  time  at  this  spot  it  slowly  passes  along  the  tube  at  the 
rate  of  20  to  30  millimetres  per  second.  This  advancing  peristaltic 
wave  normally  takes  place  in  only  one  direction,  and  so  serves  to 
drive  on  the  contents  of  the  tube. 

Involuntary  muscle  nearly  always  contains  numerous  plexuses  of 
non-medulla  ted  nerve-fibres  with  ganglion  cells ;  so  that  much  dis- 
cussion has  taken  place  on  the  question  whether  the  phenomena  of 
rhythmicality  and  peristalsis  are  properties  of  the  muscular  tissue 
itself  or  of  the  nerves  mixed  with  it.  The  evidence  available  (namely, 

140 


CH.  XIII.]  CONTRACTION   OF   INVOLUNTARY  MUSCLE  141 

that  portions  of  muscular  tissue  entirely  free  from  nerves  act  in  the 
same  way  as  those  that  possess  nerves)  indicates  that  it  is  the 
muscular  rather  than  the  nervous  tissues  that  possess  these  properties ; 
though  it  can  hardly  be  doubted  that  under  normal  conditions  the 
contraction  of  involuntary  muscle  is  influenced  and  controlled  by 
nervous  agency. 

As  instances  of  nerveless  involuntary  muscles  which  possess  the 
property  of  rhythmical  action,  we  may  take  the  ventricle  apex  of  the 
frog's  or  tortoise's  heart.  If  this  is  cut  off  and  fed  with  a  suitable 
nutritive  fluid  at  considerable  pressure  it  will  beat  rhythmically 
(Gaskell).  The  middle  third  of  the  ureter  is  another  instance  of 
muscular  tissue  free  from  nerves,  but  which  nevertheless  executes 
peristaltic  movements.  Perhaps,  however,  the  most  striking  example 
is  that  of  the  foatal  heart,  which  begins  to  beat  directly  it  is  formed, 
long  before  any  nerves  have  grown  into  it. 

The  artificial  stimuli  employed  for  involuntary  are  the  same  as 
those  used  for  voluntary  muscle ;  single  induction  shocks  are,  however, 
often  ineffectual  to  produce  contraction,  but  the  make,  and  to  a  less 
extent  the  break,  of  a  constant  current  will  act  as  a  stimulus. 

The  faradic  current  is  a  good  stimulus,  but  it  never  throws 
involuntary  muscle  into  tetanus;  in  the  heart,  strong  stimulation 
will  sometimes  effect  a  partial  fusion  of  the  beats,  but  never  complete 
tetanus.  The  rate  of  stimulation  makes  no  difference ;  in  fact,  very 
often  a  rapid  rate  of  stimulation  calls  forth  less  rapidly  occurring 
contractions  than  a  slow  rate. 

It  is  possible  to  render  the  frog's  heart  quiescent  by  tying  a 
ligature  tightly  around  the  junction  of  the  sinus  with  the  right 
auricle,  but  the  heart  can  be  made  to  contract  on  stimulating  it. 
It  is  then  found  that  the  latent  period  is  much  longer,  than  in 
voluntary  muscle ;  if  a  series  of  stimuli  are  applied,  say,  at  intervals 
of  a  second  or  two,  each  produces  a  single  heart-beat ;  the  successive 
contractions  so  obtained  show  a  well-marked  staircase  (beneficial 
effect  of  contraction,  see  p.  101).  The  strength  of  the  stimulus  in 
such  an  experiment  does  not  matter;  a  minimal  stimulus  elicits  a 
maximum  effect  ("  all  or  nothing  " — Waller). 

The  contraction  of  smooth  muscle  is  so  sluggish  that  the  various 
stages  of  latent  period,  shortening  and  relaxation,  can  be  followed 
with  the  eye;  the  latent  period  often  exceeds  half  a  second  in 
duration.  It  does  not  obey  the  "  all  or  nothing  "  law. 

The  normal  contraction  of  voluntary  muscle  is  a  kind  of  tetanus 
(see  p,  104) ;  the  normal  contraction  of  cardiac  and  plain  muscle 
is  a  much  prolonged  single  contraction.  A  very  valuable  piece 
of  evidence  in  this  direction  is  seen  in  the  experiment  on  the  heart 
with  the  physiological  rheoscope  (see  p.  128).  Each  time  the 
heart  contracts  the  rheoscopic  preparation  executes  a  single  twitch. 


142      COMPARISON  OF  VOLUNTARY  AND  INVOLUNTARY  MUSCLE    [CH.  XIII. 

not  a  tetanus.  This  is  an  indication  that  the  electrical  change  is  a 
single  one,  and  not  a  succession  of  changes  such  as  occurs  in  tetanus. 

But  though  involuntary  muscle  cannot  be  thrown  into  tetanus, 
it  has  the  property  of  entering  into  a  condition  of  sustained  contrac- 
tion called  tonus.  We  shall  have  to  consider  this  question  again  in 
connection  with  the  plain  muscular  tissue  of  the  arterioles. 

Involuntary  muscle  when  it  contracts  undergoes  thermal  and 
chemical  changes  similar  to  those  we  have  dealt  with  in  the  case  of 
the  voluntary  muscles. 

Involuntary  muscle  is  usually  supplied  with  two  sets  of  nerves, 
one  of  which  (accelerator)  increases  and  the  other  of  which  (inhibitory) 
decreases  its  activity.  The  nerve-endings  in  involuntary  muscle 
require  a  much  larger  dose  of  curare  to  affect  them  than  the  end- 
plates  in  voluntary  muscle. 

The  phenomena  of  rigor  mortis  in  involuntary  muscle  have  not 
been  so  fully  studied  as  in  the  case  of  voluntary  muscle.  It  has, 
however,  been  shown  that  the  chemical  composition  of  involuntary 
muscle  differs  in  no  noteworthy  manner  from  that  of  voluntary  muscle, 
and  on  death  the  muscle  becomes  acid ;  such  products  as  carbonic 
acid  and  sarcolactic  acid  are  formed.  In  the  heart,  stomach,  uterus, 
and  rectum,  post-mortem  rigidity  has  been  noted,  and  it  probably 
occurs  in  all  varieties  of  plain  muscle. 

Swale  Vincent  has  shown  that  the  characteristic  proteins  (paramyosinogen  and 
myosinogen)  occur  in  both  striped  and  unstriped  muscle,  and  the  heat  rigor  curves 
of  involuntary  muscle  are  practically  identical  with  those  obtained  by  Brodie  (see 
p.  139).  He  is  inclined  to  think  that  the  two  proteins  are  formed  by  the  breaking 
down  of  a  compound  protein  which  in  living  muscle  mainly  coagulates  at  47J  C. 
This  view  is  taken  by  Stewart  in  reference  to  striped  muscle  also,  but  has  been 
very  seriously  questioned  by  v.  Fiirth.  The  most  striking  chemical  difference 
between  unstriped  and  striped  muscle  is  seen  in  the  amount  of  nucleo-protein  which 
they  contain.  Plain  muscle  contains  six  to  eight  times  the  amount  found  in 
voluntary  muscle  ;  cardiac  muscle  contains  an  intermediate  quantity. 


CHAPTER  XIV 

PHYSIOLOGY   OF  NERVE 

• 

MANY  points  relating  to  the  physiology  of  nerve  have  been  already 
studied  in  connection  with  muscle.  But  there  still  remain  further 
questions  upon  which  we  have  hardly  touched  as  yet. 

Classification  of  Nerves. 

The  nerve-fibres  which  form  the  conducting  portions  of  the 
nervous  system  may  be  classified  into  three  main  groups,  according 
to  the  direction  in  which  they  normally  conduct  nerve  impulses. 
These  three  classes  are : — 

1.  Efferent  nerve-fibres. 

2.  Afferent  nerve-fibres. 

3.  Inter-central  nerve-fibres. 

1.  Efferent  or  centrifugal  nerves  are  those  which  conduct  im- 
pulses from  the  central  nervous  system  (brain  and  spinal  cord)  to 
other  parts  of  the  body.  When,  for  instance,  there  is  a  wish  to  move 
the  hand,  the  impulse  starts  in  the  brain,  and  travels  a  certain 
distance  down  the  spinal  cord ;  it  leaves  the  spinal  cord  by  one  or 
more  of  the  spinal  nerves,  and  so  reaches  the  muscles  of  the  hand, 
which  are  thrown  into  contraction.  Such  nerves  are  called  motor. 
A  list  of  the  classes  of  efferent  nerves  is  as  follows : — 

a.  Motor. 

b.  Accelerator. 

c.  Inhibitory. 

d.  Secretory. 

e.  Electrical. 
/.  Trophic. 

a.  Motor  nerves.  Some  of  these  go  to  voluntary  muscles ;  others 
to  involuntary  muscles,  such  as  the  vaso-motor  nerves  which 
supply  the  muscular  tissue  in  the  walls  of  arteries. 

143 


144  PHYSIOLOGY   OF  NEKVE  [OH.  XIV. 

b.  Accelerator  nerves  are  those  which  produce  an  increase  in  the 

rate  of  rhythmical  action.  An  instance  of  these  is  seen  in 
the  sympathetic  nerves  that  supply  the  heart. 

c.  Inhibitory  nerves  are  those  which  cause  a  slowing  in  the  rate 

of  rhythmical  action,  or  it  may  be  its  complete  cessation. 
Inhibitory  nerves  are  found  supplying  many  kinds  of 
involuntary  muscle;  a  very  typical  instance  is  found  in 
the  inhibitory  fibres  of  the  heart  which  are  contained  within 
the  trunk  of  the  vagus  nerve.* 

d.  Secretory  nerves  are  found  supplying  many  secreting  glands, 

such  as  the  salivary  glands,  gastric  glands,  and  sweat 
glands.  The  impulse  which  travels  down  a  secretory  nerve 
stimulates  secretion  in  the  gland  it  supplies. 

e.  Electrical  nerves  are  found  in  the   few  fishes   which   possess 

electrical  organs.     The  impulse  which  travels   down   these 

nerves   causes    the    electrical    organ    to    be    thrown    into 

activity. 
/.  Trophic  nerves  are  those  which  control  the  nutrition  of  the 

part  they  supply. 

2.  Afferent  or  centripetal  nerves  are  those  which  conduct 
impulses  in  the  reverse  direction,  namely,  from  all  parts  of  the 
body  to  the  central  nervous  system.  When  one  feels  pain  in  the 
finger,  the  nerves  of  the  finger  are  stimulated,  an  impulse  travels 
up  the  nerves  to  the  spinal  cord,  and  then  to  the  brain.  The  mental 
process  set  up  in  the  brain  is  called  a  sensation ;  the  sensation,  how- 
ever, is  referred  to  the  end  of  the  nerve  where  the  impulse  started, 
and  the  sensation  of  pain  does  not  appear  to  occur  in  the  brain,  but 
in  the  finger.  This  is  an  instance  of  a  sensory  nerve ;  and  the  terms 
afferent  and  sensory  may  often  be  used  synonymously.  The  nerves 
of  sensation  may  be  grouped  as  follows : — 

a.  The  nerves  of  special  sense ;  such  as,  of  sight,  hearing,  taste, 

smell,  and  touch. 

b.  The  nerves  of  general  sensibility ;  that  is,  of  a  vague  kind  of 

sensation  not  referable  to  any  of  the  special  senses ;  as  an 
instance,  we  may  take  the  vague  feelings  of  comfort  or 
discomfort  in  the  interior  of  the  body. 

c.  Nerves  of  pain.     It  is  a  moot  point  whether  these  are  anatomi- 

cally distinct  from  the  others,  but  there  is  some  evidence 

that  this  is  the  case  (see  more  fully  chapters  on  Sensation) 

The   words    "sensory"   and  "afferent,"  however,  are  not  quite 

synonymous.      Just  as  we  may  have  efferent  impulses  leaving  the 

brain  for   the   heart   or   blood-vessels   of  which   we   have   no  con- 

*  The  question  has  been  much  debated  whether  voluntary  muscle  is  provided 
with  inhibitory  nerves ;  they  do,  however,  appear  to  be  present  in  certain  nerves 
supplying  the  muscles  of  the  claws  of  lobsters  and  similar  crustaceans. 


CH.  XIV.]  REFLEX   ACTION  145 

scious  knowledge,  so  also  afferent  impulses  may  travel  to  the 
central  nervous  system  which  excite  no  conscious  feelings.  The 
afferent  nerve-tracts  to  the  cerebellum  form  a  very  good  instance  of 
these. 

Then,  too,  the  excitation  of  many  afferent  nerves  will  excite  what 
are  called  reflex  actions.  We  are  very  often  conscious  of  the  sensa- 
tions that  form  the  cause  of  a  reflex  action,  but  we  do  not  necessarily 
have  such  sensations.  Many  reflex  actions,  for  instance,  occur  during 
sleep ;  many  may  be  executed  by  the  spinal  cord  even  after  it  has 
been  severed  from  the  brain,  and  so  the  brain  cannot  be  aware  of 
what  is  occurring. 

A  reflex  action  is  an  action  which  is  the  result  of  an  afferent 
impulse.  Thus  a  speck  of  dust  falls  into*the  eye,  and  causes  move- 
ments of  the  eyelids  to  get  rid  of  the  offending  object.  The  dust 
excites  the  sensory  nerve-endings  in  the  conjunctiva,  an  impulse 
travels  to  the  centre  of  this  nerve  in  the  brain,  and  from  the  brain 
a  reflected  impulse  travels  to  the  muscles  of  the  eyelid.  As  an 
instance  of  a  reflex  action  in  which  secretion  is  concerned,  take  the 
watering  of  the  mouth  which  occurs  when  food  is  seen  or  smelt.  The 
nerves  of  sight  or  smell-  convey  an  afferent  impulse  to  the  brain, 
which  reflects,  down  the  secretory  nerves,  an  impulse  which  excites 
the  salivary  glands  to  activity. 

These,  however,  are  instances  of  reflex  action  which  are  accom- 
panied with  conscious  sensation,  but  like  all  pure  reflex  actions  are 
not  under  the  control  of  the  will. 

An  instance  of  a  reflex  action  not  accompanied  with  consciousness 
is  seen  in  a  man  with  his  spinal  cord  cut  across  or  crushed,  so  that 
any  communication  between  his  brain  and  his  legs  is  impossible. 
He  cannot  move  his  legs  voluntarily,  and  is  unconscious  of  any 
feelings  in  them.  Yet  when  the  soles  of  his  feet  are  tickled  he  draws 
his  legs  up,  the  centre  of  reflex  action  being  in  the  grey  matter  of 
the  lower  region  of  the  spinal  cord. 

For  a  reflex  action,  three  things  are  necessary :  (1)  an  afferent 
nerve,  (2)  a  nerve-centre  consisting  of  nerve-cells  to  receive  the 
afferent  impulse  and  send  out  the  efferent  impulse,  and  (3)  an 
efferent  nerve  along  which  the  efferent  impulse  may  travel.  If  the 
reflex  action  is  a  movement,  the  afferent  nerve  is  called  excito-motor ; 
if  it  is  a  secretion,  the  afferent  nerve  is  called  excito-secretory ;  and 
similarly,  afferent  nerves  may  also  be  excito-accelerator,  excito-inhibitory, 
etc. 

3.  Inter-central  nerve-fibres  are  those  which  connect  nerve- 
centres  together ;  they  connect  different  parts  of  brain,  and  of  the 
cord  to  one  another,  and  we  shall  find  in  our  study  of  the  nerve- 
centres  that  they  are  complex  in  their  arrangement. 

K 


146  PHYSIOLOGY    OF   NERVE  [CH.  XIV. 


Investigation  of  the  Functions  of  a  Nerve. 

There  are  always  two  main  experiments  by  which  the  function 
of  a  nerve  may  be  ascertained.  The  first  is  section,  the  second  is 
stimulation. 

Section  consists  in  cutting  the  nerve  and  observing  the  loss  of 
function  that  ensues.  Thus,  if  a  motor  nerve  is  cut,  motion  of  the 
muscles  it  supplies  can  no  longer  be  produced  by  activity  of  the 
nerve-centre;  the  muscle  is  paralysed.  If  a  sensory  nerve  is  cut, 
the  result  is  loss  of  sensation  in  the  part  it  comes  from. 

Stimulation  of  the  cut  nerve  is  the  opposite  experiment.  When 
a  nerve  is  cut  across,  one  piece  of  it  is  still  connected  with  the  brain 
or  spinal  cord ;  this  is  called  the  central  end  ;  the  other  piece,  called 
the  peripheral  end,  is  still  connected  with  some  peripheral  part  of 
the  body.  Both  the  central  and  the  peripheral  end  should  be  stimu- 
lated ;  this  is  usually  done  by  means  of  induction  shocks.  In  the 
case  of  a  motor  nerve,  stimulation  of  the  central  end  produces  no 
result ;  stimulation  of  the  peripheral  end  produces  a  nervous  impulse 
which  excites  the  muscles  to  contract.  In  the  case  of  a  sensory 
nerve,  stimulation  of  the  peripheral  end  has  no  result,  but  stimula- 
tion of  the  central  end  causes  a  sensation,  usually  a  painful  one,  and 
reflex  actions,  which  are  the  result  of  the  sensation. 

When  a  nerve  is  cut  across,  there  are  other  results  than  the  loss 
of  function  just  mentioned ;  for  even  though  the  nerve  is  still  left 
within  the  body  with  a  normal  supply  of  blood,  it  becomes  less  and 
less  irritable,  till  at  last  it  ceases  to  respond  to  stimuli  altogether. 
This  diminution  of  excitability  starts  from  the  point  of  section  and 
travels  to  the  periphery,  but  is  temporarily  preceded  by  a  wave  of 
increased  excitability  travelling  in  the  same  direction  (Eitter-Valli 
law). 

This  loss  of  excitability  of  nerve  is  accompanied  with  degenera- 
tive changes  which  are  of  so  great  importance  as  to  demand  a  separate 
section. 

Degeneration  of  Nerve. 

Suppose  a  nerve  is  cut  right  across,  the  piece  of  the  nerve  left  in 
connection  with  the  brain  or  spinal  cord  remains  approximately 
healthy  both  in  structure  and  functions ;  but  the  peripheral  piece  of 
the  nerve  loses  its  functions  and  undergoes  what  is  generally  called, 
after  the  discoverer  of  the  process,  Wallerian  degeneration.  A  nerve 
is  made  up  of  nerve-fibres,  and  each  nerve-fibre  is  essentially  a  branch 
of  a  nerve-cell;  when  the  nerve  is  cut,  the  axis  cylinders  in  the 
peripheral  portion  are  separated  from  the  cells  of  which  they  are 
branches  and  from  which  they  have  grown.  These  portions  of  the 


CH.  XIV.] 


DEGENERATION   OF  NERVE 


147 


axis  cylinders  which  are  cut  off  from  their  parent  cells  die,  breaking 
up  into  fragments ;  the  medullary  sheath  of  each  undergoes  a  process 
of  disintegration  into  droplets  of  myelin,  which  are  ultimately 
absorbed  and  removed  by  the  lymphatics.  At  the  same  time  there  is 
a  multiplication  of  the  nuclei  of  the  primitive  sheath.  This  degenera- 
tive process  begins  to  be  visible  microscopically  two  or  three  days 


t'  ft' 

Fio.  153.— Degeneration  and  regeneration  of  nerve-fibres.  A,  nerve-fibre,  fifty  hours  after  operation. 
my,  Medullary  sheath  breaking  up  into  myelin  drops,  p,  Granular  protoplasm,  n,  Nucleus,  g, 
Primitive  sheath  or  neurilemma.  B,  nerve-fibre  after  four  days,  cy,  Axis  cylinder  partly  broken 
up  and  enclosed  in  portions  of  myelin.  C,  a  more  advanced  stage  in  which  the  medullary  sheath 
has  almost  disappeared.  Numerous  nuclei,  n",  are  seen.  D,  commencing  regeneration ;  several 
fibres  (t',  t")  have  sprouted  from  the  somewhat  bulbous  cut  end  (6)  of  the  nerve-fibre,  a,  An  axis 
cylinder  Avhich  has  not  yet  acquired  its  medullary  sheath,  s,  s',  Primitive  sheath  of  the  original 
fibre.  (Ranvier.) 

after  the  section  has  been  made  In  the  case  of  the  non-medullated 
fibres,  there  is  no  medullary  sheath  to  exhibit  the  disintegrative 
changes  just  alluded  to;  and  the  nuclei  of  the  sheath  do  not 
multiply ;  there  is  simply  death  of  the  axis  cylinder.  The  degenera- 
tion occurs  simultaneously  throughout  the  whole  extent  of  the  nerve. 
Ranvier's  original  diagram  is  reproduced  in  fig.  153.  Fig.  154  is 
drawn  from  a  specimen  of  degenerated  fibres  stained  by  osmic  acid ; 
the  myelin  droplets  are  coloured  black  by  this  method. 


148 


PHYSIOLOGY   OF   NERVE 


[CH.  XIV. 


A  great  amount  of  attention  has  been  directed  to  this  process  of 
degeneration,  because  it  has  formed  a  valuable  method  of  research  in 
tracing  nervous  tracts,  and  ascertaining  the 
nerve-cells  from  which  they  originate.  It 
must  not,  however,  be  regarded  as  an  isolated 
phenomenon  in  physiology ;  it  is  only  an  illus- 
tration of  the  universal  truth  that  any  portion 
of  a  cell  (in  this  case  the  axis-cylinder  process) 
cut  off  from  the  nucleus  of  the  cell  degenerates 
and  dies. 


Regeneration  of  Nerve-Fibres. 

If  a  nerve  is  cut  and  allowed  to  heal, 
restoration  of  function  occurs  after  the  lapse 
of  a  variable  time,  which  can  be  shortened  if 
the  cut  ends  of  the  nerve  are  sutured  together. 
This  surgical  assistance  is  of  special  import- 
ance when  the  nerve  is  a  large  one,  and  the 
formation  of  dense  cicatricial  tissue  between 
the  ends  is  thus  minimised.  The  restoration 
of  function  is  due  to  regeneration  of  nerve- 
fibres,  which  sprout  out  from  the  central  end 
of  the  cut  nerve  and  grow  distalwards,  replacing 
those  which  have  degenerated.  The  new  fibres, 
which  are  the  earliest  to  appear,  are  of  a  much 
narrower  diameter  than  those  they  replace ; 
this  is  illustrated  in  fig.  153,  D.  Later  the 
It  is  obvious  that  a  mass  of  dense  scar  tissue 

will  hinder  the  successful  growth  of  the  nerve-fibres.  When  regene- 
ration does  not  take  place,  the  central  ends  of  the  cut  fibres  and  the 
cells  from  which  they  originate  undergo  slow  atropic  changes  (disuse 
atrophy). 

The  view  that  in  the  embryo  each  nerve-fibre  develops  as  an 
outgrowth  from  a  nerve-cell,  and  grows  in  a  distal  direction,  finally 
becoming  united  to  other  tissues  in  the  periphery  of  the  body,  is 
associated  especially  with  the  name  of  His,  and  has  been  accepted 
by  the  majority  of  embryologists.  There  have  been  other  views  held, 
but  it  will  be  sufficient  to  mention  only  one  of  these,  for  it  is  the  one 
which,  next  to  that  of  His,  has  been  favoured  by  investigators. 
Briefly  it  is  as  follows :  the  nerve-fibre  is  not  a  secondarily  formed 
bridge  between  the  central  nervous  system  and  the  peripheral 
organs,  but  exists  from  the  very  first,  and  in  subsequent  develop- 
ment it  merely  undergoes  elaboration,  and  increases  in  bulk  and 
in  length  as  the  distance  from  the  central  nervous  system  and 


1. 154. — Degenerated  nerve- 
fibres  at  an  early  stage, 
where  the  fragmentation 
of  the  medullary  sheath 
into  myelin  droplets  is 
well  shown.  Stained  by 
osmic  acid.  (S.  Martin.) 


new  fibres  are  larger. 


CH.  XIY.]  REGENERATION   OF  NERVE  149 

the  periphery  increases  with  the  increasing  size  of  the  developing 
animal. 

I  shall  not  fully  discuss  the  pros  and  cons  of  this  controversy, 
but  only  say  that  the  available  evidence  appears  to  me  strongly  in 
favour  of  the  first  of  the  two  views,  and  it  has  within  the  last  few  years 
been  supported  by  a  very  remarkable  ocular  demonstration  of  its 
truth.  Mr  Eoss  Harrison  of  the  Johns  Hopkins  University,  Balti- 
more, has  actually  seen  the  fibres  growing  outwards  in  embryonic 
structures.  Pieces  of  the  primitive  nervous  tube  which  forms  the 
central  nervous  system  were  removed  from  frog  embryos,  and  kept 
alive  in  a  drop  of  lymph  for  a  considerable  time ;  the  cilia  of  the 
neighbouring  epidermic  cells  remained  active  for  a  week  or  more ; 
embryonic  mesoblastic  cells  in  the  vicinity  were  seen  to  become 
transformed  into  striated  muscular  fibres,  and  there  was  therefore  no 
doubt  that  even  under  artificial  conditions  of  this  kind — rendered 
necessary  for  microscopic  purposes — life  and  growth  were  continuing. 
From  the  primitive  nerve-cells,  and  from  these  alone,  nerve-fibres 
were  observed  growing  and  extending  into  the  surrounding  parts. 
Each  fibre  shows  faint  fibrillation,  but  its  most  remarkable  feature 
is  its  enlarged  end,  which  exhibits  a  continual  change  of  form. 
This  amoeboid  movement  is  very  active,  and  it  results  in  drawing 
out  and  lengthening  the  fibre  to  which  it  is  attached,  and  the  length 
of  the  fibre  increases  at  the  rate  of  about  a  micro-millimetre  in  one 
'or  two  minutes.  Similar  observations  have  since  this  been  made  in 
the  embryos  of  other  animals. 

I  think  these  observations  show  beyond  question  that  the  nerve- 
fibre  develops  by  the  overflowing  of  protoplasm  from  the  central 
cells,  and  thus  give  us  direct  evidence  in  favour  of  the  view  which 
most  embryologists  previously  held  mainly  as  the  result  of  circum- 
stantial evidence.  Such,  then,  being  the  general  state  of  our 
knowledge  regarding  the  way  in  which  nerve-fibres  grow  in  the 
developing  animal,  it  is  not  surprising  to  find  that  the  prevalent  idea 
regarding  their  regeneration  after  injury  follows  the  same  lines. 
The  original  teaching  of  the  elder  Waller  (1852),  that  regeneration 
occurs  by  fibres  growing  out  from  the  central  stump  into  the 
peripheral  segment  of  the  nerve,  was  formulated  at  a  time  when  the 
relationship  of  nerve-fibres  to  nerve-cells  was  not  so  fully  recognised 
as  it  is  at  present ;  and  the  Wallerian  doctrine  may  be  accepted  with 
confidence  to-day.  It  has,  however,  been  questioned  from  time  to 
time,  and  the  earliest  to  hold  an  opposite  view  was  Vulpian. 
Vulpian,  working  with  Philippeaux,  cut  nerves  in  young  animals, 
excising  long  portions  so  as  to  prevent  the  two  ends  uniting.  Some 
months  later  they  were  surprised  to  find  that  a  number  of  new 
perfectly  formed  nerve-fibres  had  appeared  in  the  peripheral  segment, 
and  that  this  segment  possessed  the  physiological  properties  of  being 
excitable  and  capable  of  conducting  nerve  impulses.  To  this 


150  PHYSIOLOGY  OF  NEEVE  [CH.  XIV. 

phenomenon  they  gave  the  name  of  "autogenetic  regeneration." 
The  publication  of  these  results  provoked  a  long  controversy,  which 
lasted  from  1859  to  1874,  and  was  closed  at  the  latter  date  by 
Vulpian  withdrawing  his  new  idea.  He  did  so  because  in  the 
meanwhile  he  had  repeated  his  experiments  more  carefully,  and  so 
discovered  that,  although  the  ends  of  the  divided  nerve  had  not 
joined  up,  connection  with  the  central  nervous  system  had  neverthe- 
less been  re-established  by  means  of  fibres  growing  into  the  peripheral 
segment  from  other  nerves  cut  through  in  skin  and  muscle  in  the 
course  of  the  operation. 

The  controversy  has  been  revived  within  the  last  few  years,  and 
the  position  of  the  disputants  has  been  almost  exactly  the  same  as 
that  occupied  by  Waller  and  Vulpian  half  a  century  ago.  Modern 
investigators  have,  however,  the  advantage  of  being  able  to  apply 
new  methods  of  research,  and  are  provided  with  many  histological 
reagents  of  which  the  older  workers  were  destitute.  It  is,  however, 
never  safe  to  argue  entirely  from  microscopic  appearances,  for  nerve- 
fibres  may  be  simulated  by  non-nervous  structures,  and  a  strand 
that  looks  like  a  nerve-fibre  is  not  really  such  unless  it  can  be 
experimentally  shown  to  be  both  excitable  and  capable  of  conducting 
nerve  impulses. 

Vulpian's  old  doctrine  of  auto -regeneration  has  been  revived  in 
this  country  by  Ballance  and  Purves  Stewart,  and  in  Scotland  by 
Kennedy.  The  most  prominent  and  persistent  supporter  of  the 
autogenetic  theory  is,  however,  a  German  neurologist  named  Bethe. 
But  none  of  these  investigators  have  excluded  the  fallacy  which 
underlay  the  work  of  Vulpian  and  Philippeaux,  as  has  been  recently 
pointed  out  by  Langley  and  Anderson.  These  two  workers  at  first 
thought  they  also  had  obtained  evidence  of  purely  peripheral 
regeneration,  and  it  was  not  until  they  carried  out  careful  dissections 
that  they  convinced  themselves  that  union  with  the  central  nervous 
system  had  really  occurred.  The  new  nerve-fibres  which  grow  into 
the  peripheral  segment  from  other  nerves  divided  in  the  operation, 
often  do  so  by  a  devious  and  contorted  course.  If  the  number  of 
medullated  nerve-fibres  in  the  peripheral  end  is  small,  then  the 
connection  with  central  fibres  was  found  to  be  slight ;  and  in  cases 
where  no  connection  occurred  then  medullated  nerve-fibres  were 
entirely  absent.  Bethe  admits  a  variability  in  the  number  of 
medullated  fibres,  and  this,  though  easily  explicable  on  the  view 
that  such  fibres  come  by  accident  from  the  central  ends  of  divided 
nerves,  is  not  accounted  for  at  all  by  the  autogenetic  theory. 

Bethe's  views  have  been  contested  not  only  by  Langley  and 
Anderson,  but  also  by  Lugaro,  by  Kolliker,  by  Cajal,  by  Marinesco, 
by  Mott,  and  Edmunds  in  conjunction  with  myself,  and  by  numerous 
others. 


CH.  XIV.]  REGENERATION   OF  NERVE  151 

I  may  mention  a  few  of  the  experimental  results  which  have 
come  out  of  the  renewed  work  elicited  by  the  promulgation  of  the 
autogenetic  theory. 

(1)  It  is  possible  m  entirely  to  prevent  reunion  with  the  central 
ends  of  divided  nerves.     In  our  own  work  we  accomplished  this 
by  removing  a  long  stretch  of  the  main  nerve  experimented  with,  by 
making  the  skin  incision  as  small  as  possible,  and  by  inclosing  the 
top  end  of  the  peripheral  segment  in  a  cap  of  sterilised  gutta-percha. 
Under  such  circumstances  no  auto-regeneration  occurs. 

(2)  Pieces  of  nerve  may  be  transplanted  under  the  skin,  and  in 
time  a  few  fully  formed  medullated  fibres  appear  within  the  degener- 
ated bundle  of  fibres.     This  is  adduced  by  Kennedy  as  undoubted 
evidence  of  auto-genesis,  but,  again,   is   easily   explicable  on   the 
hypothesis   that   the   new  fibres  had  wandered  in  from  cutaneous 
nerves  divided  in  the  course  of  the  operation,  and  we  showed  that  if 
this  fallacy  is  excluded  by  transplanting  the  nerve,  not  into  the 
subcutaneous  tissues,  but  on  to  the  stomach  wall  in  a  sheath  of 
peritoneum,  where  invasion  by  nerves  is  practically  impossible,  no 
regeneration  occurs  at  all. 

(3)  The  late  appearance  of  the  medullary  sheath  in  those  portions 
of  the  regenerating  fibres  which  are  most  distant   from  the  place 
where  the  nerve  is  originally  cut  and  sutured,  is  a  conclusive  piece 
of  evidence  that  the  new  nerve-fibres  grew  from  the  central  end  in  a 
peripheral  direction. 

(4)  After  regeneration  has  occurred,  the  nerve  may  be  again  cut 
across,  either  on  the  central  side  of  the  original  point  of  section  (as 
in  Langley  and  Anderson's  work),  or  on  the  peripheral  side  of  the 
original  seat  of  operation  (as  in  our  own  work).     In  the  former  case 
Wallerian  degeneration  occurs  in  all  the  new  fibres,  showing  that 
they  were  all  under  the  nutritive  control  of  the  cells  of  the  central 
nervous  system     In  the  latter  case  the  degeneration   took   place 
solely  on  the  peripheral  side  of  the  second  cut.     The  direction  of 
degeneration  is  always  the  direction  of  growth,  so  this  experiment 
shows  that  the  growth  of  the  new  fibres  had  not  started  from  the 
periphery  centralwards,  but  in  the  reverse  direction.     On  looking  up 
the   literature   of   the  subject,  I  found  that  Vulpian  also  did   this 
experiment  with  the  same  result,  and  it  can  hardly  be  doubted  that 
this  formed  one  of  the  factors  that  later  led  him  to  abandon  the 
autogenetic  theory.     An  experiment  on  somewhat  the  same  lines  has 
been  carried  out  recently  by  Lugaro :  he  has  shown  that  regeneration 
of  the  cut  nerves  connected  with  the  lower  part  of  the  spinal  cord 
does  not  occur  after  that  part  of  the  spinal  cord  has  been  extirpated. 
This  is  a  very  striking  piece  of  evidence,  showing  the  dependence  of 
the  growth  of  fibres  on  the  activity  of  the  cells  of  the  central  nervous 
system  with  which  they  are  originally  connected, 


152 


PHYSIOLOGY   OF   NERVE 


[CH.  XIV. 


Cajal,  by  the  help  of  his  new  silver  method,  has  come  to  the 
conclusion  that  the  new  formation  of  nerve  axons  in  the  peripheral 
stump  is  exclusively  due  to  growth  from  the  central  end.  He 


— G 


F 


FIG.  155.— Olive-shaped  swellings  at  the  ends 
of  nerve-fibres  growing  distal  wards  from 
the  central  ends  twenty-one  days  after  the 
nerve  had  been  divided.  (Marinesco.) 


Fro.  156. — Spiral  forms  often  seen 
in  regenerating  nerve-fibres : 
the  fibres  are  seen  to  be  of 
varying  thickness,  and  each 
is  provided  with  a  terminal 
swelling.  (Marinesco.) 


figures  the  long  and  often  contorted  course  of  these  growing  fibres  in 
the  swelling  at  the  cut  central  end,  and  shows  that  they  ultimately 
reach  their  goal — the  peripheral  segment — in  time  and  in  spite  of  all 
hindrances.  The  greater  the  obstacles  interposed  the  later  does  the 


CH.  XIV.]  REGENERATION   OF  NERVE  153 

union  and  consequent  regeneration  in  the  peripheral  end  occur.  He 
also  draws  attention  to  the  olive-shaped  swelling  at  the  free  end  of 
each  growing  axis-cylinder.  These  are  also  figured  by  Marinesco, 
who  calls  attention  to  the  fact  that  these  terminal  swellings,  although 
they  may  roughly  be  described  as  olive-shaped,  vary  a  good  deal  in 
external  form;  this  is  shown  in  the  accompanying  drawings  (figs. 
155  and  156),  and  is  quite  intelligible  now  that  we  have  Boss 
Harrison's  description  of  the  constant  changes  of  form  they  exhibit 
in  embryonic  history. 

The  two  next  figures  (157  and  158)  are  drawn  from  preparations 
stained  by  Cajal's  new  method,  and  they  require  but  little  comment. 

They  show  the  new  fibres  penetrating  the  cicatricial  tissue  of  the 
junction  from  the  central  end  in  a  peripheral  direction ;  they  show 
the  absence  of  any  new  axons  developed  autogenetically  in  the 
peripheral  end.  Such  preparations  ought  to  carry  conviction  to 
those  who  have  any  lingering  belief  in  auto -regeneration,  that  the 
Wallerian  view  is  the  only  possible  one  to  adopt. 

It  must  not,  however,  be  supposed  that  the  peripheral  end  is 
entirely  inactive ;  for  while  degeneration  is  progressing  in  the  axons 
and  their  fatty  sheath,  an  active  multiplication  of  the  cells  of  the 
primitive  sheath  or  neurilemma  is  taking  place.  These  neuri- 
lemmal  cells  probably  play  a  nutritive  action  towards  the  more 
important  structures  within  them,  and  Graham  Kerr,  in  a  recent 
study  of  nerve  growth  in  the  fish  Lepidosiren,  has  supported  in  a 
very  conclusive  and  entirely  independent  way  the  view  that  Mott 
and  I  advanced  some  years  ago  of  the  value  of  the  neurilemma  in 
maintaining  the  nutrition  of  the  axis  cylinder.  There  is  but  little 
doubt  also  that  these  cells  act  as  phagocytes  in  the  removal  of  the 
degenerated  products  of  the  other  portions  of  the  nerve-fibre.  But 
after  this  is  accomplished  they  elongate  and  unite  into  long  chains. 
It  is  this  appearance  that  has  led  some  observers  into  regarding  them 
as  true  nerve-fibres ;  they  have  jumped  to  the  conclusion  that  the 
neurilemmal  cells  are  also  able  to  form  a  conducting  core,  and  so 
have  regarded  auto-regeneration  as  a  histological  possibility.  But 
all  recent  observations  by  the  best  methods,  as  I  have  already  stated, 
have  failed  to  discover  either  an  axial  core  or  a  fatty  sheath  in  these 
"  embryonic  fibres,"  as  they  have  been  termed.  Howell  and  Huber 
put  it  very  well  twenty  years  ago,  when  they  said  the  peripheral 
structures  are  able  to  prepare  the  scaffolding,  but  the  axon,  the 
essential  conducting  core  of  the  fibre,  has  an  exclusively  central  origin. 

The  change  in  the  neurilemmal  cells  which  occurs  in  the  peri- 
pheral segment  is  even  more  vigorous  at  the  central  termination  of 
the  cut  nerve ;  here  its  nutritive  function  (or  apotrophic  function,  as 
Marinesco  calls  it)  is  effective,  and  provides  for  the  nourishment  of 
the  actively  lengthening  axis  cylinders.  At  the  peripheral  end, 


FIG.  157.— Longitudinal  section  of  sciatic  nerve  of 
new-born  dog  eight  days  after  the  nerve  had 
been  divided.  Union  had  already  taken  place. 
At  the  extremity  of  the  central  end  (A)  grow- 
ing fibres  are  seen  running  in  various  direc- 
tions towards  the  cicatrix  (B);  C  is  the 
peripheral  end,  into  which  a  few  fibres  are 
already  penetrating.  (Marinesco.) 


—  TTV 


JL-  m 


C-4 


-  m 


-m 


FIG.  158.— Longitudinal  section  of  dog's  nerve, 
twenty-one  days  after  the  nerve  had  been 
divided.  A  more  advanced  condition  is  seen 
than  that  shown  in  fig.  157.  A  is  the  central 
end  ;  B  the  cicatrix  of  union,  where  the  nerve- 
fibres  are  seen  in  great  numbers  taking  an 
irregular  course.  Into  C,  the  peripheral  end, 
many  fibres  have  already  successfully  pene- 
trated;  m,  m',  m",  etc.,  are  the  terminal 
swellings  of  fibres  growing  from  the  central 
stump  and  directed  towards  the  periphery, 
except  in  the  case  of  m",  where  the  twisting 
of  the  new  fibre  in  its  efforts  to  grow  had,  at 
the  time  when  the  animal  was  killed,  directed 
the  termination  backwards.  (Marinesco,) 


CH.  XIV.] 


SPINAL   NERVE   ROOTS 


155 


unless  the  axons  reach  it,  it  is  ineffective  in  so  far  as  any  real  new 
formation  of  nerve-fibres  is  concerned.  If,  however,  the  axons  reach 
the  peripheral  segment,  the  work  of  the  neurilemmal  cells  has  not 
been  useless,  for  they  provide  the  supporting  and  nutritive  elements 
necessary  for  their  continued  and  successful  growth.  Moreover,  the 
neurilemmal  activity  appears  to  be  essential.  In  the  white  fibres  of 
the  central  nervous  system  the  neurilemma  is  absent;  in  this 
situation  not  only  is  the  removal  of  the  products  of  degeneration  a 
very  slow  process,  hut  regeneration  does  not  occur. 

Functions  of  the  Roots  of  the  Spinal  Nerves. 

The  general  truths  enunciated  in  the  two  preceding  sections  are 
well  illustrated  by  the  experiments  made  to  determine  the  functions 
of  the  roots  of  the  spinal 
nerves.  Each  spinal  nerve 
originates  from  the  spinal 
cord  by  two  roots.  One  of 
these  is  called  the  anterior  or 
ventral  root :  it  consists  of 
nerve-fibres  which  originate 
from  the  large  multipolar 
cells  in  that  portion  of  the 
grey  matter  in  the  interior 
of  the  spinal  cord  which  we 
shall  presently  learn  to  call 
the  anterior  horn.  These 
nerve-fibres  are  all  medul- 
lated ;  the  large  ones  join 
up  with  the  posterior  root 
to  form  the  spinal  nerve; 
the  small  nerve-fibres  leave 
the  root  and  pass  to  the  sym- 
pathetic chain,  which  then 
distributes  non  -  medullated 
fibres  to  the  involuntary  fibres  of  the  blood-vessels  and  viscera. 

The  other  root,  the  posterior  or  dorsal  root,  has  upon  it  a  collection 
of  nerve-cells  forming  the  spinal  ganglion.  Each  nerve-cell  is 
enclosed  within  a  nucleated  sheath  of  connective-tissue,  and  it  is 
from  these  nerve-cells  that  the  fibres  of  the  posterior  roots  grow. 
In  the  embryo,  each  nerve-cell  has  two  processes  (fig.  159,  A),  one  of 
which  grows  to  the  spinal  cord,  where  it  terminates  by  branching 
around  the  multipolar  cells  of  the  grey  matter;  the  other  process 
grows  outwards  to  the  periphery.  In  the  adult  mammal  (not  in 
fishes)  the  two  processes  coalesce  in  the  first  part  of  their  course, 
forming  a  ^-shaped  junction  (fig.  159,  B). 


B. 


FIG.  159. — A,  bipolar  cell  from  spinal  ganglion  of  a  4i 
weeks  embryo,  n,  Nucleus ;  the  arrows  indicate  the 
direction  in  which  the  nerve  processes  grow,  one  to 
the  spinal  cord,  the  other  to  the  periphery.  B,  a 
cell  from  the  spinal  ganglion  of  the  adult ;  the  two 
processes  have  coalesced  to  form  a  T-shaped  junction. 
(Diagrammatic.) 


156 


PHYSIOLOGY   OF   NERVE 


[CH.  XIV. 


The  great  discovery  that  the  anterior  roots  are  motor  and  the 
posterior  sensory  is  usually  attributed  to  Sir  Charles  Bell  (1811); 
bub  an  examination  of  his  writings  shows  that  the  deductions  he 
drew  were  incorrect.  It  was  Magendie  (1822)  who  solved  this  funda- 
mental problem,  and  Herbert  Mayo,  the  first  Professor  of  Physiology 
at  King's  College,  London,  who  elucidated  similar  facts  in  relation  to 
the  cranial  nerves  which  supply  motion  and  sensation  in  the  face 
region.  Magendie  found  that  on  section  of  the  anterior  roots  there 
resulted  paralysis  of  the  muscles  supplied  by  the  nerves ;  on  section 
of  the  posterior  roots  there  was  loss  of  sansation.  These  experiments 
clearly  pointed  to  the  conclusion  that  the  anterior  roots  contain  the 
efferent  (motor)  fibres ;  and  the  posterior  roots  the  afferent  (sensory) 
fibres.  This  conclusion  was  confirmed  by  the  experiment  of  stimula- 
tion. Stimulation  of  the  peripheral  end  of  the  cut  anterior  root  caused 
muscular  movement;  of  the  central  end,  no  effect.  Stimulation  of 

the  central  end  of  the  cut  posterior 
root  caused  pain  and  reflex  movements ; 
of  the  peripheral  end,  no  effect. 

Recurrent  sensibility. — One  of  the 
statements  just  made  requires  a  slight 
modification;  namely,  excitation  of 
the  peripheral  end  of  a  divided  an- 
terior root  will  evoke  pain  and  reflex 
movements,  as  well  as  direct  move- 
ments; that  is  to  say,  the  anterior 
root,  though  composed  mainly  of 
motor  fibres,  contains  a  few  sensory 
fibres  coming  from  the  membranes  of 
the  spinal  cord,  and  then  running 
into  the  posterior  root  with  the  rest 
of  the  sensory  fibres.  They  often,  however,  run  down  the  mixed 
nerve  a  considerable  distance  before  returning  to  the  posterior  roots. 
The  diagram  on  this  page  (fig.  160)  illustrates  the  course  of  one  of 
these  recurrent  fibres  (r) ;  the  arrows  represent  the  direction  in  which 
it  conveys  impulses. 

Degeneration  of  roots. — The  facts  in  connection  with  this  subject 
were  made  out  by  Waller,  and  may  be  best  understood  by  referring 
to  the  next  diagram  (fig.  161). 

A  represents  a  section  of  the  mixed  nerve  beyond  the  union  of 
the  roots;  the  whole  nerve  beyond  the  section  degenerates,  and  is 
consequently  shaded  black  in  the  figure. 

B  represents  the  result  of  section  of  the  anterior  root ;  only  the 
anterior  root-fibres  degenerate;  the  sensory  fibres  of  the  posterior 
root  remain  intact.  The  small  medullated  nerve-fibres  (not  shown  in 
the  diagram)  also  degenerate  as  far  as  the  ganglion  cells  of  the 


Spinal  Nerve 


FIG.  160.— Diagram  to  illustrate  recurrent 
sensibility. 


CH.  XIV.] 


SPINAL   NERVE   ROOTS 


157 


sympathetic  system  with  which  they  communicate.  The  recurrent 
sensory  fibres  in  this  root  do  not 
degenerate  with  the  others,  but 
are  found  degenerated  in  the 
part  of  the  anterior  root  at- 
tached to  the  spinal  cord. 

Section  of  the  posterior  root 
always  produces  the  same  phy- 
siological effect  (loss  of  sensa- 
tion)* wherever  the  section  is 
made,  but  the  degeneration  effect 
is  different  according  as  the  sec- 
tion is  made  on  the  proximal  or 
distal  side  of  the  ganglion.  If 
the  section  is  made  beyond  the 
ganglion,  the  degeneration  occurs 

oo    cV^-i™    in    P   Vwnrnnd    fV»o  QAP          FIG.  161.— Diagram  to  illustrate  Wallerian  degene- 
aS    Snown    in    O    Deyona    ine  Sec-  ration  of  nerve-roots. 

tion  in  the  peripheral  portion  of 

the  posterior  root-fibres ;  the  anterior  root  remains  intact  except  for 
the  recurrent  sensory  fibres  which  it  con- 
tains. If  the  section  is  made  as  in  D, 
between  the  ganglion  and  the  cord,  the  only 
piece  that  degenerates  is  the  piece  severed 
from  the  ganglion  and  running  into  the 
cord;  these  fibres  may  be  traced  up  in  the 
posterior  column  of  the  spinal  cord  until 
they  terminate  in  grey  matter,  which  they 
do  at  different  levels.  The  whole  of  the 
sensory  fibres,  including  the  recurrent  ones 
which  are  still  attached  to  the  ganglion, 
remain  histologically  healthy. 

The  accompanying  figure  (fig.  162)  is  one 
of   the    original   illustrations   made   by  Dr 
Waller,  and  I  am  indebted  to  the  present 
Dr  Waller  for  permission  to  reproduce  it. 
These   facts   of    degeneration   teach   us, 
roots  several  days  alter  sec-     what  we  also  learn  from  the  study  of  em- 

tion  of  both  roots  close  to  the      -,          ^  .-i  ,i  r>i  n     ,-t 

cord ;  the  anterior  fibres  are    bryology,  that   the  nerve-fibres  of   the  an- 
terior root  are  connected  to  the  nerve-cells 


the  nerve-ceiis  from  which    within  the  spinal  cord,  while  the  posterior 

they  grew,  are  normal.  ,      ,     .        . ,  ,-f        .    , , 

root-fibres  are  connected  to  the  cells  01  tne 
spinal  ganglia ;  or,  to  put  it  another  way,  the  trophic  centres  which 

*  In  order  to  obtain  any  appreciable  loss  of  motion  or  sensation,  it  is  necessary 
to  divide  several  roots  (anterior  or  posterior  as  the  case  may  be),  as  there  is  a  good 
deal  of  overlapping  in  the  peripheral  distribution  of  the  fibres. 


158  PHYSIOLOGY   OF   NERVE  [CH.  XIV 

control  the  nutrition  of  the  fibres  are  situated  within  the  cord  for  the 
anterior  roots,  and  within  the  spinal  ganglia  for  the  posterior  roots. 

Changes  in  a  Nerve  during  Activity. 

When  a  nerve  is  stimulated,  the  change  produced  in  it  is  called  a 
nervous  impulse ;  this  change  travels  along  the  nerve,  and  the  pro- 
pagation of  some  change  is  evident  from  the  effects  which  follow : 
sensation,  movement,  secretion,  etc. ;  but  in  the  nerve  itself  very  little 
change  can  be  detected.  There  is  no  change  in  form ;  the  most  deli- 
cate thermopiles  have  failed  to  detect  any  production  of  heat,  and 
we  are  almost  completely  ignorant  of  any  chemical  changes.  The 
only  alteration  which  can  be  readily  detected  as  evidence  of  this 
molecular  change  in  a  nerve  is  the  electrical  one.  Healthy  nerve  is 
iso-electric,  but  during  the  passage  of  a  nervous  impulse  along  it 
there  is  a  very  rapid  diphasic  variation,  which  travels  at  the  same 
rate  as  the  nervous  impulse.  This  is  similar  to  the  diphasic  change 
in  muscle,  and  can  be  detected  and  measured  in  the  same  way. 

Waller  regards  the  current  of  action  of  any  excitable  tissue  as  an  index  of  the 
magnitude  of  action,  and  records  the  movement  of  the  galvanometer  by  photograph- 
ing the  excursion  of  the  spot  of  light  on  a  moving  photographic  plate.  He  has  in 
this  way  obtained  records  from  muscle,  nerve,  retina,  skin,  plant  tissues,  etc.  He 
points  out  that  the  only  available  index  of  action  within  the  nerve  itself  is  this 
electrical  sign  of  activity,  whereas  in  muscle  the  mechanical  action  can  be  compared 
with  its  accompanying  electrical  changes.  The  amount  of  contraction  in  a  muscle 
caused  by  excitation  of  its  nerve  is  only  a  very  rough,  or  even  a  fallacious,  indica- 
tion of  the  excitability  of  the  nerve,  because  the  nerve  is  connected  to  the  muscle  by 
motor  end-plates,  and  these,  as  we  have  already  seen,  are  fatigued  long  before  the 
nerve  shows  any  sign  of  fatigue. 

Using  this  method,  Waller  has  obtained  a  number  of  interesting  results  on  the 
variation  in  nerve  action  produced  by  drugs  and  other  agents.  He  finds  that  the 
effect  of  carbonic  acid  is  to  cause  a  diminution,  and  finally  disappearance  of  the 
galvanometric  response  ;  when  this  gas  is  replaced  by  air  the  nerve  recovers,  and  the 
action-currents  increase.  Ether  acts  similarly  ;  but  with  chloroform  recovery  is 
difficult  to  obtain.  Small  doses  of  carbonic  acid  increase  the  action-currents,  and 
Waller  considers  that  the  staircase  effect  in  muscle  (p.  101),  and  the  similar  progres- 
sive increase  noted  in  the  action-currents  of  nerve  as  the  result  of  repeated  stimula- 
tion are  due  to  the  evolution  of  this  gas  during  activity. 

This  hypothesis  has  been  recently  confirmed  by  Bseyer  and  Frohlich.  They 
have  shown  that  peripheral  nerves  participate  in  respiratory  exchanges,  using  up 
oxygen  and  producing  carbonic  acid  in  minute  but  measurable  amounts.  In  the 
absence  of  oxygen,  stimulation  ceases  after  some  hours  to  evoke  the  activity  of  a 
nerve,  but  on  readmission  of  the  gas  recovery  is  almost  instantaneous.  The  store 
of  oxygen  so  obtained  will  again  keep  up  nervous  activity  for  a  considerable 
time  even  although  no  fresh  oxygen  is  supplied.  This  illustrates  the  great  power 
nerve  has  in  repairing  itself  and  in  storing  oxygen. 

There  can  be  no  doubt  that  the  existence  of  the  electrical  variation  is  as  a  rule 
the  index  of  the  excitatory  alteration  in  a  nerve.  But  in  the  present  state  of  our 
knowledge  we  are  not  justified  in  assuming  that  it  gives  an  absolutely  faithful 
record.  The  electrical  variation  can  be  detected  in  a  nerve  for  many  days  after  its 
removal  from  the  body ;  although  the  electrical  change  is  a  concomitant  of  the 
real  excitatory  process,  the  former  may  be  therefore  perceptible  when  other  evidence 
of  the  existence  of  the  latter  fails.  Moreover,  Gotch  and  Burch  have  obtained 
further  evidence  of  the  dissociation  of  the  electrical  response  from  the  excitatory 
process.  In  the  frog's  sciatic  nerve,  it  is  possible  with  two  stimuli  in  rapid  sue- 


CH.  XIV.]  VELOCITY    OF   NERVE   IMPULSES  159 

cession  to  obtain  only  one  electrical  response  near  the  seat  of  excitation  which  has 
been  cooled,  while  two  such  responses  occur  in  a  more  peripheral  warmer  region. 

Excitability  and  conductivity.  — It  is  necessary  to  distinguish  between  these  two 
properties  of  nerve.  Changes  in  excitability,  and  in  the  power  of  conducting  nerve 
impulses,  do  not  necessarily  go  together,  as  shown  in  the  following  experiment : — 
The  nerve  of  a  frog's  leg  is  led  through  a  glass  tube,  the  ends  of  which  are  sealed 
with  clay,  care  being  taken  that  the  nerve  is  not  compressed.  The  tube  is  provided 
with  an  inlet  and  outlet,  so  that  gases  may  be  passed  through  it.  Two  pairs  of 
electrodes  are  arranged,  so  that  the  nerve  can  be  stimulated  either  within  or  outside 
the  little  gas  chamber.  If  carbon  dioxide  or  ether  vapour  is  passed  through  the 
tube,  both  excitability  and  conductivity  are  in  time  abolished,  but  excitability 
disappears  first ;  at  this  stage,  if  the  nerve  is  stimulated  by  an  induction  shock 
inside  the  tube,  the  muscle  does  not  respond,  but  on  stimulating  the  nerve  at  the 
end  distant  from  the  muscle  and  outside  the  tube,  the  muscle  contracts.  The  nerve, 
therefore,  is  not  excitable,  though  it  will  conduct  impulses.  At  a  later  stage  shocks 
administered  by  either  pair  of  electrodes  provoke  no  contraction.  When  the 
poisonous  vapour  is  replaced  by  air,  the  nerve  recovers,  and  conductivity  returns 
before  excitability.  If  alcohol  vapour  is  used  conductivity  is  stated  to  vanish  before 
excitability. 

Gotch  has  shown  that  cold  applied  to  a  nerve  acts  very  much  like  carbonic 
acid.  Intense  cold  will  cause  disappearance  of  both  excitability  and  conductivity ; 
but  cold  of  such  a  degree  which  abolishes  the  excitability  of  the  nerve  to  induction 
shocks,  increases  its  excitability  to  the  constant  current,  and  also  to  mechanical 
stimuli. 

Velocity  of  a  Nerve  Impulse. 

This  may  be  measured,  as  was  first  done  by  Helmholtz,  in  motor 
nerves  as  follows :  a  muscle-nerve  preparation  is  made  with  as  long 
a  nerve  as  possible ;  the  nerve  is  stimulated  first  as  near  to  the 
muscle,  and  then  as  far  from  the  muscle,  as  possible.  The  moment 
of  stimulation  and  the  moment  of  commencing  contraction  is 
measured  by  taking  muscle-tracings  on  a  rapidly  moving  surface  in 
the  usual  way,  with  a  time- tracing  beneath.  The  contraction  ensues 
later,  when  the  nerve  is  stimulated  at  a  distance  from  the  muscle, 
than  in  the  other  case,  and  the  difference  in  the  two  cases  gives 
the  time  occupied  in  the  passage  of  the  impulse  along  the  piece  of 
nerve,  the  length  of  which  can  be  easily  measured. 

A  similar  experiment  can  be  performed  on  man  by  means  of  the 
transmission  myograph  (see  p.  105).  If  a  tracing  of  the  contraction 
of  the  thumb  muscles  is  taken,  the  two  stimuli  may  be  successively 
applied  through  the  moistened  skin,  first  at  the  brachial  plexus  below 
the  clavicle;  and  secondly,  at  the  median  nerve  at  the  bend  of 
the  elbow. 

The  same  method  may  be  employed  in  man  for  determining  the 
rate  of  transmission  in  sensory  nerves.  A  man  is  told  to  make  a 
given  signal,  such  as  to  open  a  key  in  an  electrical  circuit,  when  he 
receives  a  stimulus  such  as  an  induction  shock  applied  to  one  of  his 
toes;  the  time  between  the  excitation  and  the  reply  is  easily 
measured.  A  second  experiment  is  then  performed  in  the  same  way, 
except  that  the  stimulus  is  applied  to  another  part  of  his  body ;  for 
instance,  his  knee.  The  time  interval  is  again  measured,  and  found 


160  PHYSIOLOGY   OF   NERVK  [CH.  XJV. 

to  be  shorter;  the  difference  between  the  time  intervals  in  the  two 
experiments  will  obviously  measure  the  time  occupied  by  the  impulse 
in  traversing  a  stretch  of  nerve  equal  to  the  distance  between  his  toe 
and  his  knee. 

Another  method,  largely  employed  by  Bernstein,  is  to  take  the 
electrical  change  as  the  indication  of  the  impulse.  A  stimulus  is 
applied  to  one  end  of  a  long  nerve,  and  the  change  in  the  electrical 
condition  of  the  nerve  is  recorded  by  a  galvanometer  connected  to 
the  other  end  of  the  nerve.  The  time  between  the  application  of 
the  stimulus  and  the  galvanometric  reply  is  measured. 

The  velocity  of  the  nerve  impulse  has  by  such  experiments  been 
found  to  vary  with  temperature,  and  to  be  approximately  the  same 
in  both  motor  and  sensory  nerves.  In  cold-blooded  animals  it  is 
thus  slower  than  in  warm-blooded  animals.  In  the  frog,  for  instance, 
at  ordinary  room  temperature  it  averages  27  metres  per  second.  In 
man,  at  normal  body  temperature  it  is  120  metres  per  second.  In  the 
case  of  non-medullated  fibres  the  velocity  is  much  slower;  these 
observations  have  been  chiefly  made  on  invertebrate  animals ;  in  the 
non-medullated  nerves  of  the  lobster  it  is  6,  and  in  the  octopus  only 
2  metres  per  second,  and  values  lower  than  these  have  been  recorded 
in  other  cases. 

Direction  of  a  Nerve  Impulse. 

Nerve  impulses  are  conducted  normally  in  only  one  direction :  in 
efferent  nerves  from,  in  afferent  nerves  to,  the  nerve-centres.  But 
there  are  some  experiments  which  point  to  the  conduction  occurring 
under  certain  circumstances  in  both  directions. 

Thus,  in  the  galvanometer  experiment  just  described,  if  the  nerve 
is  stimulated  in  the  middle  instead  of  at  one 
end,  the  electrical  change  (the  evidence  of  an 
impulse)  is  found  to  be  conducted  towards  both 
ends  of  the  nerve. 

Kuhne's  gracilis  experiment  proves  the  same 
point.  The  gracilis  muscle  of  the  frog  (fig. 
163)  is  in  two  portions,  with  a  tendinous  in- 
tersection, and  supplied  by  nerve-fibres  that 
branch  into  two  bundles;  excitation  strictly 
limited  to  one  of  these  bundles,  after  division 
of  the  tendinous  intersection,  causes  both  por- 
tions of  the  muscle  to  contract. 

Another  striking  experiment   of   the  same 
"IG>1'lfte?wa]1JeSr0)ffrog-     kind   can   be   performed  with   the   nerve  that 
supplies  the  electrical  organ  of  Malapterurus. 
This  nerve  consists  of  a  single  axis  cylinder  and  its  branches ;  stimu- 
lation of  its  posterior  free  end  causes  the  "  discharge  "  of  the  electrical 


CH.  XIV.]  CKOSSING   OF   NKBVES  161 

organ,  although  the  nervous  impulse  normally  travels  in  the  opposite 
direction. 

Crossing  of  Nerves. 

Some  experiments  designed  to  prove  the  possibility  of  nervous 
conduction  in  both  directions  were  performed  many  years  ago  by 
Paul  Bert.  He  grafted  the  tip  of  a  rat's  tail  either  to  the  back  of 
the  same  rat,  or  to  the  nose  of  another.  When  union  had  been 
effected,  the  tail  was  amputated  near  its  base.  After  a  time,  irritation 
of  the  end  of  the  trunk -like  appendage  on  the  back  or  nose  of  the 
rat  gave  rise  to  sensation.  The  impulse  thus  passed  from  base  to 
tip,  instead  of  from  tip  to  base,  as  formerly.  This  experiment  does 
not,  however,  prove  the  point  at  all ;  for  all  the  original  nerve-fibres 
in  the  tail  must  have  degenerated,  and  the  restoration  of  sensation 
was  due  to  new  fibres,  which  had  grown  into  the  tail.  Exactly  the 
same  objection  holds  to  another  series  of  experiments,  in  which  the 
motor  and  sensory  nerves  of  the  tongue  were  divided  and  united 
crosswise.  Eestoration  of  both  movement  and  sensation  does  occur, 
but  is  owing  to  new  nerve-fibres  growing  out  from  the  central  stumps 
of  the  cut  nerves. 

Though  these  experiments  do  not  prove  what  they  were  intended 
to,  they  are  of  considerable  interest  in  themselves.  Dr  E.  Kennedy 
has  recently  carried  out  a  very  careful  piece  of  work  on  this  question 
of  nerve-crossing.  He  cut  in  a  dog's  thigh  the  nerves  supplying 
the  flexor  and  the  extensor  muscles,  and  sutured  them  together 
crosswise.  Eegeneration  of  structure  and  restoration  of  function 
occurred  equally  quickly,  as  in  those  cases  in  which  the 
central  ends  had  been  united  to  the  peripheral  ends  of  their  own 
proper  nerves.  On  examining  the  cortex  of  the  brain  in  those 
animals  in  which  nerve-crossing  had  been  accomplished,  it  was 
found  that  stimulation  of  the  region  which  in  a  normal  animal  gave 
flexion,  now  gave  extension  of  the  limb,  and  vice  versd. 

A  series  of  equally  important  experiments  have  also  been  carried 
out  by  Langley,  in  which  he  shows  that  the  same  facts  are  true  for 
the  nerves  that  supply  involuntary  muscle.  These  nerve-fibres 
will  under  certain  experimental  conditions  terminate  by  arborising 
around  other  nerve-cells  than  those  which  they  normally  form 
connections  (synapses)  *  with.  It  will  be  sufficient  to  give  one 
typical  experiment.  If  the  vagus  nerve  is  cut  across  in  the  neck,  its 
peripheral  end  degenerates  downwards ;  if  the  cervical  sympathetic 
is  cut  across  below  the  superior  cervical  ganglion,  its  peripheral  end 
degenerates  upwards,  as  far  as  the  ganglion.  If  subsequently  the 
central  end  of  the  cut  vagus  is  united  to  the  peripheral  end  of  the 

The  meaning  of  the  term  "  synapse  "  is   fully  explained  in  Chapter   XVI. 

(p.  188). 

L 


162 


PHYSIOLOGY   OF   NERVE 


[Cll.  XiV. 


cub  sympathetic,  in  the  course  of  some  weeks  the  vagus  fibres  grow 
into  the  sympathetic  and  form  synapses  around  the  cells  of  the 
superior  cervical  ganglion,  and  stimulation  of  the  united  nerve  now 
produces  such  effects  as  are  usually  obtained  when  the  cervical 
sympathetic  is  irritated ;  for  instance,  dilatation  of  the  pupil,  raising 
of  the  upper  eyelid,  and  constriction  of  blood-vessels  of  the  head  and 
neck'.  (See  accompanying  diagram,  fig.  164.) 

Such  experiments  as  these  are  important  because  they  teach  us 
that  though  the  action  of  nerves  may  be  so  different  in  different 
cases  (some  being  motor,  some  inhibitory,  some  secretory,  some 

A  B  C 


Superior! 
Cervical  i 
Ganglion 


§.:: 


FIG.  164.— Diagram  to  illustrate  Langley's  experiment  on  vagus  and  cervical  sympathetic  nerves.  In 
A,  the  two  nerves  are  shown  intact ;  the  direction  of  the  impulses  they  normally  carry  is  shown  by 
arrows,  and  the  names  of  some  of  the  parts  they  supply  are  mentioned.  In  B,  both  nerves  are  cut 
through.  The  degenerated  portions  are  represented  by  discontinuous  lines.  In  C,  the  union 
described  in  the  text  has  been  accomplished,  and  stimulation  at  the  point  a'  now  produces  the  same 
results  as  were  in  the  intact  nerves  (A)  produced  by  stimulation  at  a. 

sensory,  etc.),  after  all  what  occurs  in  the  nerve  trunk  itself  is 
always  the  same ;  the  difference  of  action  is  due  to  difference  either 
in  the  origin  or  distribution  of  the  nerve-fibres.  If  we  remember 
the  familiar  illustration  in  which  nerve  trunks  are  compared  to 
telegraph  wires,  we  may  be  helped  in  realising  this.  The  destina- 
tion of  a  certain  group  of  telegraph  wires  may  be  altered,  and  the 
alteration  may  produce  different  consequences  at  different  places ; 
the  electric  change,  however,  in  the  wires  would  be  the  same  in  all 
cases.  So  the  nerve  impulse  going  along  a  nerve  is  always  the  same 
sort  of  molecular  disturbance ;  if  it  is  made  as  in  the  experiment  just 
described,  to  go  by  a  wrong  channel,  it  produces  just  the  same  results  as 
though  the  impulse  had  reached  its  destination  by  the  usual  channel. 


CH.  XIV.]  NATURE   OF   THE    NERVE   IMPULSE  163 

The  Nature  of  the  Nerve  Impulse. 

What  is  the  nature  of  this  change  which  we  have  provisionally 
been  alluding  to  as  a  molecular  disturbance  ?  The  ancients  imagined 
the  nerves  were  tubes  along  which  a  flow  of  a  spiritual  essence 
(animal  spirits)  took  place.  We  know  that  this  is  not  the  case,  but 
we  do  not  know  anything  else  about  it  for  certain.  Theories  there 
are  in  plenty,  but  none  of  them  are  adequate  to  explain  the  pheno- 
menon. The  theories  fall  under  two  main  headings,  chemical  and 
physical.  In  a  chemical  theory  we  may  compare  the  transmission  of 
the  impulse  to  the  propagation  of  a  flame  along  a  train  of  gunpowder ; 
but  such  an  analogy  is  very  imperfect,  for  the  gunpowder  is  entirely 
consumed,  and  has  not  the  power  to  repair  itself  as  a  nerve  has. 
Nevertheless  there  are  certain  facts  which  make  a  chemical  theory 
acceptable ;  these  are : — 

(1)  Analogy  with  muscle,  where  the  propagation  of  the  muscular 
impulse  is  undoubtedly  largely  due  to  the  propagation  of  chemical 
disturbances. 

(2)  Evidence  that  the  nerve  does  undergo  metabolic  changes,  as 
shown  by  the  necessity  for  oxygen,  and  the  production  of  minute 
amounts  of  carbon  dioxide. 

(3)  Arrhenius  and  van  't  Hoff  showed  that  a  rise  of  10°  in  tem- 
perature increases  the  velocity  of  a  chemical  reaction  to  two  or  three 
times  its  original  rate.     Purely  physical  changes  are  not  accelerated 
nearly  so  greatly  by  the  same  rise  of  temperature.     Maxwell's  recent 
experiments  show  that  a  rise  of  10°  C.  approximately  doubles  the 
velocity  of   nerve   conduction,   and    the   conclusion   is   drawn  that, 
therefore,   the   nerve   impulse  is   a   chemical   phenomenon.     Keith 
Lucas  confirmed  this  observation.     Woolley  obtained  the  same  figure 
from  the  influence  of  temperature   on   the   rate   of   conduction   in 
muscle,  so  probably  the  conduction  process  is  of  a  similar  nature  in 
both  tissues. 

The  physical  theories  in  relation  to  this  question  compare  the 
nerve  impulse  to  the  way  in  which  an  electrical  change  is  propagated 
along  a  wire.  When  the  electrical  accompaniment  of  nervous 
activity  was  first  discovered  this  view  was  unhesitatingly  accepted 
by  many  physiologists,  and  the  current  of  action  was  regarded  not  as 
an  accidental  concomitant  of  the  impulse,  but  as  the  change  which 
really  constitutes  the  essence  of  the  impulse,  and  which  serves  to 
excite  the  chemical  and  other  changes  in  the  tissues  to  which  the 
nerve  is  distributed.  Two  facts,  however,  stood  out  at  once  which 
rendered  the  adoption  of  this  simple  view  difficult ;  one  of  these  is 
the  slow  rate  of  conduction  in  nerve ;  and  the  other  is  the  pheno- 
menon of  inhibition ;  it  is  quite  conceivable  that  an  electrical  dis- 
turbance, feeble  though  it  be,  can  fire  off  an  excitable  tissue  and  lead 


164  PHYSIOLOGY  OF  NERVE  [CH.  XIV. 

to  increase  in  its  activity ;  it  is  much  more  difficult  to  understand 
how  it  can  possibly  produce  a  lessening  of  action  such  as  occurs  in 
inhibition.  .Nevertheless  the  "discharge  hypothesis,"  as  it  used  to 
be  called,  has  been  revived  of  late  in  modified,  form,  and  electrolytic 
changes  with  liberation  of  ions  occurring  between  the  fibrils  and  the 
interfibrillar  material  are  supposed  to  constitute  the  main  feature  of 
the  impulse.  Macdonald  considers  that  the  potassium  salts  in  organic 
combination  within  the  axis  cylinder  are  the  principal  materials  that 
undergo  the  change  which  is  propagated  along  the  nerve;  he  thus 
reduces  the  phenomenon  of  nervous  conduction  to  electrolytic  dis- 
sociation and  association  of  inorganic  ions.  The  comparatively  slow 
rate  at  which  the  change  is  propagated  must,  if  this  is  so,  be  due  to 
admixture  or  combination  of  the  salt  with  the  less  mobile  colloid 
substances  of  the  conducting  core.  It  is  interesting  to  state,  if  only 
in  outline,  the  kind  of  theories  which  are  in  the  air  at  present.  We 
must  await  with  patience  to  see  whether  they  or  any  of  them  contain 
a  germ  of  truth,  or  whether,  like  so  many  theories  in  the  past,  they 
will  be  forgotten  in  the  future. 

Receptive  Substances. 

Langley,  as  a  result  of  the  study  of  certain  poisons  on  various 
tissues  and  organs,  has  made  the  interesting  suggestion  that  in  all 
cell-protoplasm  two  classes  of  constituents  at  least  are  present :  (1)  a 
chief  substance  or  substances  concerned  with  the  main  function  of 
the  cell ;  and  (2)  receptive  substances  which  may  be  acted  upon  by 
chemical  materials,  or  in  certain  cases  by  nervous  stimuli.  The 
receptive  substance  affects,  or  can  affect,  the  metabolism  of  the  chief 
substance.  A  cell,  for  instance,  can  contain  a  motor  receptive  sub- 
stance, or  an  inhibitory  receptive  substance,  or  both,  and  the  effect  of 
a  nerve  impulse  will  then  depend  on  the  proportion  of  the  jbwo 
kinds  of  receptive  substance  which  is  affected  by  the  impulse. 

Eeceptive  substances  are  at  present  entirely  hypothetical,  and  we 
have  no  knowledge  of  their  chemical  composition.  The  assumption 
that  they  exist  does,  however,  explain  certain  difficulties,  particularly 
in  the  action  of  such  drugs  as  nicotine  and  curare,  which  are  agents 
that  act  on  nerve-endings  in  muscle.  If  the  receptive  substances 
really  exist,  the  drugs  mentioned  probably  act  on  them  and  not  on 
the  nerve-endings  proper. 

In  support  of  the  new  theory,  Dixon  has  shown  that  chemical 
substances  are  produced  in  the  heart  during  inhibition  which  can  be 
dissolved  out  by  alcohol,  and  then  used  to  produce  inhibition  in 
another  heart. 

The  theory  is  an  attractive  one,  but  is  not  much  more  than  a 
theory  at  present.  If,  however,  a  muscle  is  rendered  active  by  the 


CIT.  XIV.] 


CHEMISTRY   OF  NERVE 


165 


production  of  a  chemical  material  which  plays  the  part  of  a  stimulus, 
and  if  it  is  rendered  inactive  by  the  production  of  chemical  changes 
of  an  opposite  kind,  we  really  only  throw  the  difficulty  further  back ; 
for  we  do  not  know  how  it  is  that  the  nervous  impulses  produce 
these  chemical  effects  on  the  receptive  substance  or  substances. 

Chemistry  of  Nervous  Tissues. 

Fresh  nervous  tissue  is  alkaline  to  litmus,  but  like  most  other 
living  structures,  it  turns  acid  after  death;  this  change  is  more 
rapid  in  grey  than  in  white  matter.  The  acidity  is  due  to  sarco- 
lactic  acid. 

Nervous  tissues  contain  a  high  percentage  of  water ;  the  following 
table  gives  the  mean  of  a  large  number  of  analyses  I  have  made: — 


Percentage  of 

Water. 

Solids. 

Proteins  in 

Solids. 

Cerebral  grey  matter 

83-5 

16-5 

51 

white      , 

69'9 

30-1 

33 

Cerebellum  . 

79-8 

20-2 

42 

Spinal  cord  as  a  whole 
Cervical  cord 

71-6 
72-5 

28-4 
27-5 

31 
31 

Dorsal  cord 

69'8 

30-2 

28 

Lumbar  cord 

72-6 

27-4 

33 

Sciatic  nerves 

65-1 

34-9 

29 

Proteins.  The  above  table  shows  also  the  high  percentage  of 
protein  which  is  present.  In  grey  matter  where  the  cells  are 
prominent  structures  this  is  most  marked,  protein  here  comprising 
more  than  half  of  the  solids  present. 

The  most  abundant  protein  is  nucleo-protein,  and  micro-chemical 
observations  have  shown  that  the  granules  in  nerve-cells  (Nissl's 
granules)  which  stain  readily  with  methylene  blue  and  other  basic 
dyes  are  nucleo-protein  in  nature.  There  is  also  a  certain  amount 
of  globulin,  which,  like  the  paramyosinogen  of  muscle,  is  coagulated 
by  heat  at  a  low  temperature  (in  mammals  47°  C).  Neurokeratin, 
which  is  especially  abundant  in  white  matter,  is  also  present. 

A  nerve,  or  a  strip  of  the  central  nervous  system,  shortens  when 
it  is  heated;  this  "heat  contraction"  occurs  in  a  series  of  steps, 
which,  as  in  the  case  of  muscle,  take  place  at  the  coagulation 
temperatures  of  the  proteins  present.  The  first  step  in  the  shorten- 
ing occurs  in  the  frog  at  about  40°,  in  the  mammal  at  about  47°,  and 
in  the  bird  at  about  52°  C.  The  nerve  is  killed  at  the  same 
temperatures. 

Lipoids.    These  are  also  abundant  constituents  of  nervous  tissue ; 


166  PHYSIOLOGY  OF   NERVE  [CH.  XIV. 

they  will  be  more  fully  studied  in  Chapter  XXVIII. ;  we  will  therefore 
for  the  present  merely  state  that  they  comprise : — 

1.  P/wsphatides,  or  phosphorised  fats.     Of   these  lecithin  is  the 
best  known ;  kephalin  and  sphingomyelin  are  others. 

2.  Gfalactosides ;    these    are    nitrogenous    glucosides    free    from 
phosphorus ;  they  yield  on  hydrolysis  the  reducing  sugar  galactose. 

3.  Cholesterin  or  cholesterol,  a  crystalline  monatomic  alcohol  of 
the  terpene  series.     Its  formula  is  C27H45OH. 

The  following  are  some  recent  analyses  of  nerve  by  Falk,  the 
numbers  given  are  percentages  of  the  total  solids  :— 

Medullated  NOT. -med  ill  later! 

nerve.  nerve. 

Cholesterin        .  .  .  25 '0  47*0 

Lecithin  .  .  .  2 '9  9-8 

Kephalin  .  .  .  12-4  23 '7 

Galactosides     .  .  .  18 '2  6'0 

Lecithin  is  a  type  of  the  phosphatides,  and  we  may  contrast  its 
decomposition  products  with  those  obtained  from  a  fat.  An 
ordinary  fat  contains  the  elements  carbon,  hydrogen,  and  oxygen, 
and  when  it  takes  up  water  it  is  split  or  hydrolysed  into  its  con- 
stituent parts,  glycerin  and  fatty  acid. 

Lecithin  (C42H84NP09)  contains  not  only  carbon,  hydrogen,  and 
oxygen,  but  nitrogen  and  phosphorus  as  well.  When  it  is  hydrolysed, 
it  yields  not  only  glycerin  and  a  fatty  acid,  but  also  phosphoric  acid, 
and  a  nitrogenous  base  termed  choline. 

Lecithin  +  water. 

L 

Glycerin.  Fatty  acid  Phosphoric  acid.  Choline. 

(usually  oleic  acid). 

Choline  is  an  ammonium-like  base,  which  contains  three  methyl 
(CE8)  groups.  Its  formula  is  N(CH3)3CH2 .  CH2(OH)2,  and  when  it 
breaks  up,  trimethylamine  N(CH3)3  is  one  of  its  decomposition 
products. 

Extractives.  Small  quantities  of  numerous  other  organic  sub- 
stances are  included  under  this  general  term ;  creatine,  xanthine,  hypo- 
xanthine,  inosite,  lactic  acid,  uric  acid,  and  urea  have  been  identified. 

Inorganic  salts.  The  proportion  of  mineral  salts  amounts  to  a 
little  more  than  1  per  cent,  of  the  total  solids.  Potassium  salts  are 
the  most  abundant.  \Ve  have  already  noted  that  Macdonald 
attributes  many  of  the  phenomena  of  nervous  action  to  electrolytic 
changes  in  these  potassium  salts,  though  his  views  on  that  question 
should  for  the  present  be  accepted  with  caution  (p.  164). 

Macallum  uses  for  the  micro-chemical  detection  of  potassium  an  acid  solution  of 
cobalt  nitrite,  and  precipitates  in  situ  the  yellow  hexanitrate  of  cobalt  and  potassium, 


CIT.  XIV.]  CHEMISTRY    OF   NERVE   DEGENERATION  167 

which  is  turned  black  on  the  addition  of  ammonium  sulphide.  His  principal 
results  are  : — potassium  is  found  in  cell  protoplasm,  but  more  abundantly  in  inter- 
cellular material ;  in  striped  muscle  it  is  limited  to  the  dark  bands,  and  in 
pancreatic  cells  to  the  granular  zone.  It  is  not  discoverable  in  any  nuclei,  nor  in 
nerve-cells,  but  in  nerve-fibres  is  found  in  patches  external  to  the  axis  cylinder. 
Macdonald  points  out  that  these  are  spots  which  have  been  injured,  and  it  is 
apparently  only  on  injury  that  the  potassium  is  liberated  in  a  form  which  renders  it 
detectable  by  Macalhim's  reagent. 

Chemical  changes  in  nervous  tissues  during  activity.  This  is 
an  almost;  unknown  field.  No  change  of  reaction  can  be  detected 
in  nerves  after  the  most  prolonged  stimulation.  The  only  thing  known 
for  certain  is  that  oxygen  is  essential,  especially  for  the  activity  of 
grey  matter ;  cerebral  anaemia  is  rapidly  followed  by  loss  of  conscious- 
ness and  death.  The  slight  respiratory  changes  which  can  be  detected 
in  peripheral  nerves  have  already  been  considered  on  p.  158.  It 
can  hardly  be  doubted  that  the  phosphatides,  which  are  extremely 
labile  substances,  participate  in  metabolism ;  and  Hans  Meyer  has 
pointed  out  that  anaesthetics  such  as  chloroform  and  ether  are 
soluble  in  lipoids,  and  that  this  interaction  may  by  lessening 
oxidative  processes  lead  to  the  production  of  unconsciousness. 

Chemical  changes  in  degenerative  conditions.  In  Wallerian 
degeneration  of  nerve,  several  investigators  have  attempted  to  dis- 
cover how  the  degenerated  nerve  differs  from  a  healthy  nerve. 
Little  or  no  change  in  the  peripheral  end  can  be  detected  up  to 
about  three  days  after  a  nerve  has  been  divided,  and  the  nerve-fibres 
remain  excitable  up  to  that  time.  They  then  show  a  progressive 
increase  in  the  quantity  of  water,  and  a  corresponding  decrease  in  the 
proportion  of  solids.  The  percentage  of  phosphorus  also  decreases, 
and  it  entirely  disappears  in  a  little  more  than  three  weeks  after 
the  nerve  is  cut.  When  regeneration  occurs,  the  nerves  return 
approximately  to  their  previous  composition. 

It  has  also  been  shown  that  in  spinal  cords  in  which  a  unilateral 
degeneration  of  the  pyramidal  tract  has  been  produced  by  a  lesion 
in  the  opposite  cerebral  hemisphere,  there  is  a  similar  increase  of 
water  and  diminution  of  phosphorus  on  the  degenerated  side. 
Further,  in  a  divided  nerve  Noll  has  shown  that  the  phosphorised 
material  also  diminishes  somewhat  in  the  central  end,  due  to 
"disuse  atrophy." 

This  disappearance  of  phosphorus  must  be  due  to  the  break-up  of 
phosphatides,  and  the  liberation  of  phosphoric  acid  which  is  carried 
away  as  phosphates  by  the  lymph  and  blood. 

The  staining  reactions  of  a  degenerated  nerve  also  indicate  that 
the  appearances  are  not  only  due  to  a  breakdown  in  an  anatomical 
sense,  but  in  a  chemical  sense  also.  Of  these  staining  reactions  the 
one  most  often  employed  is  that  which  is  associated  with  the  name 
of  Marchi.  This  is  the  black  staining  which  the  medullary  sheaths 


168  PHYSIOLOGY  OF   NERVE  [CH.  XIV. 

of  degenerated  nerve-fibres  show  when  after  being  hardened  in 
Miiller's  fluid  they  are  treated  with  Marchi's  reagent,  a  mixture 
of  Miiller's  fluid,  and  osmic  acid.  Healthy  nerve-fibres  are  not 
blackened  by  this  reagent,  because  the  more  rapidly  penetrating 
chromic  acid  of  the  Miiller's  fluid  has  already  supplied  the  unsaturated 
oleic  acid  radical  in  the  lecithin  and  other  phosphatides  with  all  the 
oxygen  they  can  take  up.  But  when  the  nerve  is  degenerated,  the 
oleic  acid  is  either  increased  in  amount,  or  so  liberated  from  its 
previous  combination  in  the  lecithin  molecule,  that  it  is  then  able 
also  to  take  oxygen  from  osmic  acid  and  reduce  it  to  a  lower  black 
oxide.  In  the  later  stages  of  degeneration  the  Marchi  reaction  is 
not  obtained,  because  the  fat  globules  have  then  been  absorbed. 

In  certain  diseases  of  the  central  nervous  system,  such  as  general 
paralysis  of  the  insane,  degeneration  occurs  on  a  large  scale,  and  the 
products  of  the  chemical  disintegration  of  the  cerebral  tissue  have 
been  sought  for  in  the  blood,  but  with  more  profitable  results  in  the 
cerebro-spinal  fluid.  This  fluid  under  those  circumstances  shows  an 
excess  of  protein  which  is  mainly  nucleo-protein ;  cholesterin  can 
also  be  usually  detected  in  the  fluid,  and  so  also  can  choline  or  some 
similar  base  which  originates  from  the  decomposition  of  phosphatides. 
Although  many  physiologists  have  taken  up  the  choline  question 
and  the  methods  for  identifying  this  base,  it  must  be  admitted  that 
the  tests  hitherto  devised  are  not  absolutely  conclusive,  for  sufficient 
of  the  base  cannot  be  collected  for  a  complete  analysis.  The  base 
which  is  present  if  not  choline  is  a  nearly  related  substance,  perhaps 
a  derivative  of  choline,  and  according  to  the  latest  researches  the 
questionable  material  is  trimethylamine,  which  we  have  already 
seen  is  a  cleavage  product  of  choline. 

Cerebro-spinal  fluid.  This  plays  the  part  of  the  lymph  of  the 
central  nervous  system,  but  it  differs  considerably  from  all  other 
forms  of  lymph.  It  is  a  very  watery  fluid,  containing  besides  some 
inorganic  salts  similar  to  those  of  the  blood  a  trace  of  protein  matter 
(globulin)  and  a  small  amount  of  sugar.  Normally  it  contains 
neither  nucleo-protein,  cholesterin,  or  choline,  and  practically  no 
cells.  Colourless  corpuscles,  however,  occur  in  it  in  inflammatory 
conditions.  There  is  no  doubt  that  the  fluid  is  a  true  secretion,  and 
that  the  cells  which  secrete  it  are  the  cubical  epithelial  cells  which 
cover  the  choroid  plexuses.  The  choroid  structure  may  indeed  be 
spoken  of  as  the  choroid  gland  ;  only  it  differs  from  other  glands  in 
having  the  secreting  epithelium  on  its  outer  surface.  Injection  of  an 
extract  of  the  choroid  plexuses  into  the  circulation  causes  a  very 
rapid  increase  in  the  flow  of  the  cerebro-spinal,  fluid  which  can  be 
collected  from  a  cannula  thrust  into  the  subcerebellar  space,  or 
into  the  lumbar  region  of  the  spinal  canal. 


CHAPTEE   XV 


ELECTROTONUS 

WHEN  a  constant  current  is  thrown  into  a  nerve,  there  is  an  excita- 
tion which  leads  to  a  nervous  impulse,  and  this  produces  a  contraction 
of  the  muscle  at  the  end  of  the  nerve.  Similarly,  there  is  another 
contraction  when  the  current  is  taken  out.  While  the  current  is 
flowing  through  the  nerve,  the  muscle  is  quiescent.  But  while  the 
current  is  flowing  there  are  changes  in  the  nerve,  both  as  regards  its 
electrical  condition  and  its  excitability.  These  changes  are  summed 
up  in  the  expression  electrotonus. 

In  the  investigation  of  this  subject  the  instruments  employed  are 
the  same  as  those  already  studied,  with  the  addition  of  two  others 
that  it  will  be  convenient  to  describe  before  passing  on  to  the  study 
of  electrotonus  itself.  These  are  the  reverser  or  commutator,  and 
the  rheochord. 

Pohl's  commutator  is  the  form  of  reverser  generally  employed.  It 
consists  of  a  block  of  ebonite  provided  with  six  pools  of  mercury, 


FIG.  165.— Pohl's  Commutator,  with  cross  wires.    (After  Waller.) 

each  of  which  is  provided  with  a  binding  screw.  The  corner  pools 
are  connected  by  diagonal  cross  wires,  and  by  a  cradle  consisting  of 
an  insulating  handle  fixed  to  two  arcs  of  copper  wire  which  can  be 
tilted  so  that  the  two  middle  pools  can  be  brought  into  communication 
with  either  of  the  two  lateral  pairs  of  pools.  Fig.  165  shows  how,  by 


170 


ELECTKOTONUS 


[Cil.  XV. 


altering  the  position  of  the  cradle,  the  direction  of  the  current  from 
one  electrode  to  the  other  is  reversed.  The  numbers  1,  2,  3,  etc., 
indicate  the  path  of  the  current  in  the  two  cases. 

Sometimes  the  reverser  is  used  without  the  cross  wires  for  a  different  purpose. 
The  battery  wires  are  connected  as  before  with  the  middle  mercury  pools.  Each 
lateral  pair  of  pools  is  connected  by  wires  to  a  pair  of  electrodes.  The  two  pairs  of 
electrodes  may  be  applied  to  two  portions  of  a  nerve,  or  to  two  different  nerves,  and 
by  tilting  the  cradle  to  right  or  left  the  current  can  be  sent  through  one  or  the  other 
pair  of  electrodes. 

The  rJieochord  is  an  instrument  by  means  of  which  the  strength  of 
a  constant  current  passed  through  a  nerve  may  be  varied.  It  consists 
of  a  long  wire  (r,  r,  r)  of  high  resistance  stretched  on  a  board.  This 
is  placed  as  a  bridge  on  the  course  of  the  battery  current.  (See  fig. 
166.)  The  current  is  thus  divided  into  two  parts:  one  part  through 


NenTe 
FIG.  166.— Simple  Rheochord. 

the  bridge,  the  other  through  the  nerve,  which  is  laid  across  the  two 
non-polarisable  electrodes  at  the  ends  of  the  wires.  The  resistance 
through  the  bridge  is  varied  by  the  position  of  the  slider  (s  s).  The 
farther  the -slider  is  from  the  battery  end  of  the  instrument  the 
longer  is  the  bridge,  and  the  higher  its  resistance,  so  that  less  current 
goes  that  way  and  more  to  the  nerve. 

The  next  figure  shows  the  more  complicated  form  of  rheochord 
invented  by  Poggendorf.     The  number  of  turns  of  wire  is  greater,  so 


FIG.  167. — Poggendorfs  Rheochord. 


that  the  resistance  can  be  varied  to  a  much  greater  extent  than  in 
the  simpler  form  of  the  instrument. 


CH.  XV.]  ELECTROTONIC   CURRENTS  171 

The  term  "  electrotonus "  includes  two  sets  of  changes  in  the 
nerve ;  first  an  electrical  change,  and  secondly  changes  in  excitability 
and  conductivity.  We  will  take  the  electrical  change  first. 

Electrotonic  currents. — The  constant  current  is  passed  through 
the  nerve  from  a  battery,  non-polarisable  electrodes  being  used ;  it  is 
called  the  polarising  current.  If  portions  of  the  nerve  beyond  the 
electrodes  are  connected  ("led  off")  as  in  the  diagram  (fig.  168)  by 
non-polarisable  electrodes  to  galvanometers,  a  current  will  in  each 
case  be  indicated  by  the  swing  of  the  galvanometer  needles.  The 
electrotonic  current  in  the  neighbourhood  of  the  negative  pole  or 
kathode  is  called  the  Teat 'electrotonic  current ;  and  that  in  the  neighbour- 
hood of  the  anode  is  called  the  anelectrotonic  current.  In  both  cases  the 
electrotonic  current  has  the  same  direction  as  the  polarising  current. 
These  currents  are  dependent  on  the  physical  integrity  of  medullated 


Anelectrotonic 
Current 

r\ 

0  —  n 

Katelectrotonic 
Current 

r\ 

Polarising  " 
Current 

T  T 

FIG.  168.— Electrotonic  currents. 

nerve;  they  are  not  found  in  muscle,  tendon,  or  non -medullated 
nerve ;  they  are  absent  or  diminished  in  dead  or  degenerated  nerve. 
They  can,  however,  be  very  successfully  imitated  in  a  model  made  of 
zinc  wire  encased  in  cotton  soaked  with  salt  solution.  The  electro- 
tonic  currents  must  be  carefully  distinguished  from  the  normal 
current  of  action,  which  is  a  momentary  change  rapidly  propagated 
with  a  nervous  impulse  which  may  be  produced  by  any  method  of 
stimulation.  The  electrotonic  currents  are  produced  only  by  an 
electrical  (polarising)  current;  they  vary  in  intensity  with  the 
polarising  current,  and  last  as  long  as  the  polarising  current  passes 
through  the  nerve. 

After  the  polarising  current  is  removed,  after-electrotonic  currents   occur   in 
different  directions  in  the  three  regions  tested. 

(«)  In  the  intrapolar  region,  the  after-current  is  opposite  in  direction  to  the 

original  polarising  current ;  unless  the  polarising  current  is  strong  and  of 

short  duration,  when  it  is  in  the  same  direction. 

(b)  In  the  katelectrotonic  region,  the  after-current  has  the  same  direction  as  the 

katelectrotonic  current. 

(c)  In  the  anelectrotonic  region,  the  after-current  has  at  first  the  same,  then 

the  opposite  direction  to  the  anelectrotonic  current. 


172 


ELECTROTONUS 


[CH.  XV. 


The  experiment  known  as  the  paradoxical  contraction  depends 
upon  electrotonic  currents.  The  sciatic  nerve  of  the  frog  divides 
in  the  lower  part  of  the  thigh  into  two  parts.  If  one  division  is 
cut  across,  and  its  central  end  stimulated  electrically  (the  spinal  cord 
having  been  previously  destroyed),  the  muscles  supplied  by  the  other 
branch  contract,  because  the  nerve-fibres  in  this  branch  have  been 
stimulated  by  the  electrotonic  variation  in  the  divided  branch. 

This  experiment  must  be  carefully  distinguished  from  Kuhne's  gracilis 
experiment  described  on  p.  160.  In  the  gracilis  experiment  the  nerve-fibres 
themselves  branch,  and  any  form  of  stimulation  applied  to  one  branch  will  cause 
contraction  of  both  halves  of  the  muscle.  In  the  paradoxical  contraction,  the 
bundles  of  nerve-fibres  are  merely  bound  side  by  side  in  the  sciatic  trunk ;  there  is 
therefore  no  possibility  of  conduction  of  a  nerve  impulse  in  both  directions ;  the 
stimulus,  moreover,  must  be  an  electrical  one. 

Electrotonic  alterations  of  excitability  and  conductivity. — 

When  a  constant  current  is  passed  through  a  nerve,  the  excitability 
and  conductivity  of  the  nerve  are  increased  in  the  region  of  the 
kathode,  and  diminished  in  the  region  of  the  anode.  When  the 
current  is  taken  out  these  properties  are  temporarily  increased  in 
the  neighbourhood  of  the  anode,  and  diminished  in  that  of  the 
kathode. 

This  may  be  shown  in  the  case  of  a  motor  nerve  by  the  following 
experiment.  The  next  diagram  represents  the  apparatus  used. 


Cell 


Key 


EXCITING 


FIG.  169.— Diagram  of  apparatus  used  in  testing  electrotonic  alterations  of  excitability. 

An  exciting  circuit  for  single  induction  shocks  is  arranged  in  the 
usual  way,  the  exciting  electrodes  being  placed  on  the  nerve  near  the 
muscle.  A  polarising  circuit  is  also  arranged,  and  includes  a  battery, 
key,  and  reverser ;  the  current  is  passed  into  the  nerve  by  means  of 
non-polarisable  electrodes.  When  the  polarising  current  is  thrown 
into  the  nerve,  or  taken  out,  a  contraction  of  the  muscle  occurs,  but 
these  contractions  may  be  disregarded  for  the  present. 

The  exciting  circuit  is  arranged  with  the  secondary  coil  so  far  from 
the  primary  that  the  muscle  responds  to  break  only,  and  the  tracing 


CH.  XV.] 


CHANGES   IN   EXCITABILITY 


173 


may  be  recorded  on  a  stationary  blackened  cylinder.  The  cylinder  is 
moved  on  a  short  distance,  and  this  is  repeated.  The  height  of  the 
lines  drawn  may  be  taken  as  a  measure  of  the  excitability  of  the  nerve. 
The  polarising  current  is  then  thrown  in,  in  a  descending  direction 
(i.e.  towards  the  muscle) ;  the  kathode  is  thus  the  non-polarisable 
electrode  near  to  the  exciting  electrodes.  While  the  polarising  current 
is  flowing,  take  some  more  tracings  by  breaking  the  exciting  current. 
The  increase  in  the  excitability  of  the  nerve  is  shown  by  the  much 
larger  contractions  of  the  muscle;  probably  a  contraction  will  be 
obtained  now  at  both  make  and  break  of  the  exciting  current.  After 
removing  the  polarising  current,  the  contractions  obtained  by  excit- 
ing the  nerve  will  be  for  a  short  time  smaller  than  the  normal,  but 
soon  return  to  their  original  size. 

Exactly  the  reverse  occurs  when  the  polarising  current  is  ascend- 
ing, i.e.  from  the  muscle  towards  the  spinal  cord.  The  non-polarisable 
electrode  near  the  exciting  electrodes  is  now  the  anode.  While  the 
polarising  current  is  passing,  the  excitability  of  the  nerve  is  diminished 
so  that  induction  shocks  which  previously  produced  contractions  of  a 
certain  size,  now  produce  smaller  contractions,  or  none  at  all.  On 
removing  the  polarising  current,  the  after-effect  is  increase  of  excit- 
ability. 

The  following  figure  is  a  reproduction  of  a  tracing  from  an  actual 
experiment.  The  after-effects 
are  not  shown.  N  represents 
a  series  of  contractions  ob- 
tained when  the  nerve  is 
normal,  K  when  it  is  kat- 
electrotonic,  A  when  it  is 
anelectrotonic. 

Exactly  similar  results  are 
obtained  if  one  uses  mechani- 
cal stimuli  instead  of  in- 
duction shocks.  The  best 
mechanical  form  of  stimulus 
is  to  allow  drops  of  mercury 
to  fall  on  the  nerve. 

The  same  is  true  for 
chemical  stimuli.  If  the  ex- 
citing electrodes  are  removed, 
and  salt  sprinkled  on  the 
nerve  near  the  muscle,  the  latter  soon  begins  to  quiver ;  its  con- 
tractions are  increased  by  throwing  in  a  descending  and  diminished 
by  an  ascending  polarising  current. 

The  increase  in  irritability  is  called  katelectrotonus,  and  the 
decrease  is  called  anelectrotonus.  The  accompanying  diagram  (fig. 


FIG.  170.— Electrotonus.     M,  make.    B,  break. 


174 


ELECTROTONUS 


[CFI.  XY. 


171)  shows  how  the  effect  is  most  intense  at  the  points  (a,.k)  where 
the  electrodes  are  applied,  and  extends  in  gradually  diminishing 
intensity  on  each  side  of  them.  Between  the  electrodes  the  increase 
shades  off  into  the  decrease,  and  it  is  evident  that  there  must  be  a 


FIG.  171. — Diagram  illustrating  the  effects  of  various  intensities  of  the  polarising  current,  n,  ri,  Nerve, 
a,  anode  ;  k,  kathode  ;  the  curves  above  indicate  increase,  and  those  below  decrease  of  irritability; 
and  when  the  current  is  small  the  increase  and  decrease  are  both  small,  with  the  neutral  point  near 
n,  and  as  the  current  is  increased  in  strength,  the  changes  in  irritability  are  greater,  and  the  neutral 
point  approaches  fc. 

neutral  point  where  there  is  neither  increase  nor  decrease  of  irritability. 
The  position  of  this  neutral  point  is  found  to  vary  with  the  intensity 
of  the  polarising  current — when  the  current  is  weak  the  point  is 
nearer  the  anode,  when  strong  nearer  the  kathode. 

Pfliiger's  law  of  contraction.  —The  constant  current  sometimes 
causes  a  contraction  both  at  make  and  break,  sometimes  at  make  only, 
sometimes  at  break  only.  The  difference  depends  on  the  strength  and 
direction  of  the  current;  and  follows  from  the  electrotonic  changes  of 
excitability  and  conductivity  we  have  been  studying.  Increase  of  ex- 
citability acts  as  a  stimulus ;  so  that  at  the  make  the  kathode  is  the 
stimulating  electrode,  and  at  the  break  the  anode  is  the  stimulating 
electrode. 

The  facts  may  be  demonstrated  in  the  following  way  (fig.  172); 


Cell 


Key 


FIG.  172. — Arrangement  of  apparatus  for  demonstrating  Pfliiger's  law. 


from  a  battery  lead  the  wires  to  the  middle  screws  of  a  reverser  (with 
cross  wires),  interposing  a  key ;  from  one  pair  of  end  screws  of  the 
reverser  lead  wires  to  the  binding  screws  of  the  rheochord ;  from  these 
same  screws  of  the  rheochord  the  non-polarisable  electrodes  lead  to 
the  nerve  of  a  nerve-muscle  preparation.  The  strength  of  the  current 


CII.  XV.] 


PFLUGEU'S  LAW  OF  CONTRACTION 


175 


is  varied  by  tho  slider  S.  The  nearer  S  is  to  the  binding  screws  the 
less  is  the  resistance  in  the  rheochord  circuit,  and  the  less  the  current 
through  the  nerve.  With  a  weak  current,  a  contraction  occurs  at 
make  only.  With  a  stronger  current  (ascending  or  descending) 
contraction  occurs  both  at  make  and  break.  With  a  very  strong 
current  (six  Groves),  the  contraction  occurs  only  at  make  with  a 
descending  current ;  and  only  at  break  with  an  ascending  current.. 

The  contractions  produced  in  the  muscle  of  a  nerve-muscle 
preparation  by  a  constant  current  have  been  arranged  in  a  table 
which  is  known  as  Ffliiger's  Law  of  Contraction. 


STRENGTH  OF 
CURRENT  USED. 

Veak   . 
Moderate 
Jtrong  . 

DESCENDING  CURRENT. 

ASCENDING  CURRENT. 

Make. 

Break. 

Make. 

Break. 

Yes. 

Yes. 
Yes. 

No. 
Yes. 
No. 

Yes. 
Yes. 
No. 

No. 
Yes. 
Yes. 

The  increase  of  irritability  at  the  kathode  when  the  current  is 
made  is  greater,  and  so  more  potent  to  produce  a  contraction  than  the 
rise  of  irritability  at  the  anode  when  the  current  is  broken ;  and  so 
with  weak  currents  the  only  effect  is  a  contraction  at  the  make. 
But  when  the  strength  of  the  current  is  increased  the  rise  of 
excitability  is  in  all  cases  sufficient  to  provoke  a  contraction 
(moderate  effect  in  above  table).  The  alteration  in  conductivity 
is  not  sufficient  to  prevent  the  impulses  being  propagated  to  the 
muscle. 

With  strong  currents  the  case  is  a  little  more  complicated, 
because  here  the  diminution  of  conductivity  is  so.  great  that  certain 
regions  of  the  nerve  become  impassable  by  nerve  impulses.  When 
the  current  has  an  ascending  direction,  the  impulse  at  the  break  is 
started  at  the  anode,  and  as  this  is  next  to  the  muscle  there  is  no 
hindrance  to  the  propagation  of  the  impulse,  but  at  the  make  the 
impulse  started  at  the  kathode  is  blocked  by  the  extreme  lowering 
of  conductivity  at  the  anode.  When  the  current  is  descending  the 
kathode  is  near  the  muscle,  and  so  the  impulse  at  make  reaches  the 
muscle  without  hindrance ;  but  at  the  break,  the  impulse  started  at 
the  anode  has  to  traverse  a  region  of  nerve,  the  conductivity  of  which 
is  so  lessened  that  the  excitation  is  not  propagated  to  the  muscle. 

G.  N.  Stewart  has  stated  in  opposition  to  the  foregoing  statements  that  at  the 
make  conductivity  is  most  lowered  at  the  kathode,  and  at  the  break  at  the  anode. 
In  other  words,  conductivity  and  excitability  vary  in  opposite  directions.  His 
results  have,  however,  not  been  accepted  by  other  physiologists,  and  are  due  to  a 
complex  set  of  excitatory  and  polarisation  changes  produced  by  the  galvanometric 
methods  he  adopted.  Gotch's  much  more  trustworthy  experiments  with  the 


176  ELECTROTONUS  [CH.  XV. 

electrometer  are  directly  opposed  to  those  of  Stewart.  ,  The  following  simple 
experiment  devised  by  Gotch  appears  to  be  quite  conclusive  that  conductivity  like 
excitability  is  lessened  at  the  anode  when  the  current  is  made.  Three  non-polaris- 
able  electrodes  are  employed  (fig.  173),  the  current  is  first  closed  from  A2  to  K,  and 
the  time  which  intervenes  before  the  muscle  contracts  is  measured ;  it  is  then 
closed  from  Aj  to  K,  and  the  time  again  measured.  In  both  cases,  excitation 
occurs  at  K,  but  the  time  of  response  in  the  second  case  (Ax  to  K)  is  longer,  because 
in  that  case  the  nerve  impulse  has  to  traverse  a  region  of  nerve  at  Ax  in  which  the 
power  of  conduction  is  lessened. 


A2  A! 

FIG.  173. — Diagram  to  illustrate  Gotch's  experiment  with  triple  electrodes. 

Sometimes  (when  the  preparation  is  specially  irritable)  instead  of 
a  simple  contraction  a  tetanus  occurs  at  the  make  or  break  of  the 
constant  current.  This  is  due  to  chemical  (electrolytic)  changes  pro- 
duced by  the  current,  and  is  liable  to  occur  at  the  break  of  a  strong 
ascending  current  which  has  been  passing  for  some  time  into  the 
preparation,  or  at  the  make  of  a  strong  descending  current;  both 
being  conditions  which  increase  the  excitability  of  the  piece  of  nerve 
nearest  to  the  muscle ;  this  is  called  Ritter's  tetanus,  and  may  be 
stopped  in  the  first  case  by  throwing  in  the  current  in  the  same 
direction,  or  in  the  second  case  by  throwing  in  a  current  in  the 
opposite  direction,  i.e.,  by  conditions  which  lessen  the  irritability  of 
this  piece  of  nerve. 

The  same  general  laws  hold  for  muscle  as  well  as  for  nerve,  but 
are  more  difficult  to  demonstrate ;  the  main  fact,  however,  that  the 
kathode  is  the  stimulating  electrode  at  the  make,  and  the  anode  at 
the  break,  may  be  easily  shown  by  the  following  experiment:  if  a 
curarised,  that  is,  a  physiologically  nerveless  muscle,  is  arranged,  as 
in  the  experiment,  for  demonstrating  the  muscle-wave  (see  fig.  122, 
p.  100),  and  a  non-polarisable  electrode  placed  at  each  end,  the  muscle- 
wave  at  the  make  of  a  constant  current  starts  at  the  kathode  and 
at  the  break  it  starts  at  the  anode. 

An  induced  current  in  the  secondary  circuit  of  an  inductorium 
may  be  regarded  as  a  current  of  such  short  duration  that  the  opening 
and  closing  are  fused  in  their  effects.  This  is  true  for  all  induction  cur- 
rents, whether  produced  by  the  make  or  break  of  the  primary  circuit. 
The  kathode  will  always  be  the  more  effective  in  causing  contraction. 

EESPONSE  OF  HUMAN  MUSCLES  AND  NERVES  TO  ELECTRICAL 
STIMULATION. 

Perhaps  the  most  important  outcome  of  this  study  of  the  response 
of  muscle  and  nerve  to  electrical  stimulation  is  its  application  to  the 
muscles  and  nerves  of  the  human  body,  because  here  it  forms  a  most 
valuable  method  of  diagnosis  in  cases  of  disease. 


CH.  XV.]  LAW   OF  CONTRACTION   IN    MAN  177 

In  the  normal  state,  nerves  can  be  stimulated  through  the 
moistened  skin  either  by  induction  shocks,  or  by  the  make  and  break 
of  a  constant  current.  In  the  case  of  the  motor  nerves  this  is  shown 
by  the  contraction  of  the  muscles  they  supply ;  and  in  the  case  of  the 
sensory  nerves  by  the  sensations  that  are  produced.  In  the  case  of 
the  sensory  nerves,  the  sensation  produced  by  the  constant  current 
is  most  intense  at  the  instant  of  make  and  break,  or  when  the 
strength  of  the  current  is  changed  in  the  direction  either  of  diminution 
or  increase;  but  there  is  a  slight  sensation  due  doubtless  to  the 
electrotonic  alterations  in  excitability  which  we  have  been  studying, 
during  the  whole  time  that  the  current  is  passing. 

When  the  nutrition  of  the  nerves  is  impaired,  much  stronger 
currents  of  both  the  induced  and  constant  kinds  are  necessary  to 
evoke  muscular  contractions  than  in  the  normal  state.  When  the 
nerves  are  completely  degenerated  (as,  for  instance,  when  they  are  cut 
off  from  the  spinal  cord,  or  when  the  cells  in  the  cord  from  which 
they  originate  are  themselves  degenerated,  as  in  infantile  paralysis) 
no  muscular  contraction  can  be  obtained  on  stimulating  the  nerves 
even  with  the  strongest  currents. 

The  changes  in  the  excitability  of  the  muscles  are  less  simple, 
because  in  them  there  are  two  excitable  structures,  the  terminations 
of  the  nerves,  and  the  muscular  fibres  themselves.  Of  these,  the 
nerve-fibres  are  the  more  sensitive  to  induction  currents,  and  the 
faradic  stimulation  of  a  muscle  under  normal  circumstances  is  by 
means  of  these  motor  nerve-endings.  Thus  we  find  that  its  excita- 
bility corresponds  in  degree  to  that  of  the  motor  nerve  supplying  it. 
The  muscular  fibres  are,  even  in  the  normal  state,  less  sensitive  to 
faradism  (that  is,  a  succession  of  induction  shocks)  than  the  nerve, 
because  they  are  incapable  of  ready  response  to  stimuli  so  very  short 
in  duration  as  are  the  shocks  of  which  a  faradic  current  consists. 
The  proof  of  this  consists  in  the  fact  that  under  the  influence  of 
curare,  which  renders  the  muscle  practically  nerveless,  the  muscle 
requires  a  much  stronger  faradic  current  to  stimulate  it  than  in  the 
normal  state.  When  the  nerve  is  degenerated,  the  make  or  break 
of  the  constant  current  stimulates  the  muscle  as  readily  as  in  the 
normal  state;  but  the  contraction  is  propagated  more  slowly  than 
that  which  occurs  when  the  nerve-fibres  are  intact,  and  is  due  to  the 
stimulation  of  the  muscular  fibres  themselves.  The  fact  that,  under 
normal  circumstances,  the  contraction  which  is  caused  by  the  constant 
current  is  as  quick  as  that  produced  by  an  induction  shock,  is  ground 
for  believing  that  in  health  the  constant,  like  the  induced  current, 
causes  the  muscle  to  contract  chiefly  by  exciting  the  motor  nerves 
within  it. 

When  the  motor  nerve  is  degenerated,  and  will  not  respond  to 
any  form  of  electrical  stimulation,  the  muscle  also  loses  all  its  power  of 

M 


178  ELECTROTONUS  [cil.  XV. 

response  to  induction  shocks.  The  nerve -degeneration  is  accompanied 
by  changes  in  the  nutrition  of  the  muscular  fibres,  as  is  evidenced 
by  their  rapid  wasting,  and  any  power  of  response  to  faradism  they 
possessed  in  the  normal  state  is  lost.  But  the  response  of  the  muscle 
to  the  constant  current  remains,  and  is  indeed  more  ready  than  in 
health,  doubtless  in  consequence  of  nutritive  changes  which  develop 
what  the  older  pathologists  called,  truly  enough,  "  irritable  weakness." 
There  is,  moreover,  a  qualitative  as  well  as  a  quantitative  change. 
In  health  the  first  contraction  to  occur  on  gradually  increasing  the 
strength  of  the  current  is  at  the  negative  pole,  when  the  circuit  is 
closed  (see  Pfluger's  law),  and  a  stronger  current  is  required  before 
closure-contraction  occurs  at  the  positive  pole.  But  in  the  morbid 
state  we  are  discussing,  closure-contraction  may  occur  at  the  positive 
pole  as  readily  as  at  the  negative  pole.  This  condition  is  called 
the  "  Reaction  of  Degeneration" 

Suppose  a  patient  comes  before  one  with  muscular  paralysis. 
This  may  be  due  to  disease  of  the  nerves,  of  the  cells  of  the  spiual 
cord,  or  of  the  brain.  If  the  paralysis  is  due  to  brain  disease,  the 
muscles  will  be  slightly  wasted  owing  to  disuse,  but  the  electrical 
irritability  of  the  muscles  and  nerves  will  be  normal,  as  they  are 
still  in  connection  with  the  nerve-cells  of  the  spinal  cord  that  control 
their  nutrition.  But  if  the  paralysis  is  due  to  disease  either  of  the 
spinal  cord  or  of  the  nerves,  this  nutritive  influence  can  no  longer 
be  exercised  over  the  nerves  or  muscles.  The  nerves  will  degenerate ; 
the  muscles  waste  rapidly;  the  irritability  of  the  nerves  to  both 
forms  of  electrical  stimulation  will  be  lost;  the  muscles  will  not 
respond  to  the  faradic  current,  but  in  relation  to  the  constant  current 
they  will  exhibit  what  we  have  called  the  "  reaction  of  degeneration." 

This  illustrates  the  value  of  the  electrical  method  as  a  means  of 
diagnosis,  that  is,  of  finding  out  what  is  the  matter  with  a  patient. 
It  is  also  a  valuable  means  of  treatment ;  by  making  the  muscles  con- 
tract artificially,  their  nutrition  is  kept  up  until  restoration  of  the 
nerves  or  nerve-centres  is  brought  about.  Another  illustration  will 
indicate  that  the  facts  regarding  electrotonic  variation  of  excitability 
are  true  for  sensory  as  well  as  for  motor  nerves;  in  a  case  of 
neuralgia,  relief  will  often  be  obtained  by  passing  a  constant  current 
through  the  nerve ;  but  the  pole  applied  to  the  nerve  must  be  the 
anode  which  produces  diminution  of  excitability,  not  the  kathode 
which  produces  the  reverse. 

Waller  has  pointed  out  that  Pfliiger's  law  of  contraction,  as  formulated  for 
frogs'  muscles  and  nerves,  is  true  for  human  muscles  and  nerves  in  the  main,  but 
there  are  certain  discrepancies.  These  arise  from  the  method  necessarily  employed 
in  man  being  different  from  those  used  with  a  muscle-nerve  preparation.  In  a 
muscle-nerve  preparation  the  nerve  is  dissected  out,  the  two  electrodes  placed  on 
it,  and  the  current  has  of  necessity  to  traverse  the  piece  of  nerve  between  the  two 
electrodes.  In  man,  the  current  is  applied  by  means  of  electrodes  or  rheophores 


GIL  XV.]  REACTION   OF  DEGENERATION  179 

which  consist  of  metal  discs  covered  with  wash  leather,  and  soaked  in  brine.  One 
of  these  is  placed  on  the  moistened  skin  over  the  nerve,  and  the  other  on  some 
indifferent  point,  such  as  the  back.  The  current  finds  its  way  from  one  electrode  to 
the  other,  not  necessarily  through  the  nerves  to  any  great  extent  (though  it  will  be 
concentrated  at  the  nerve  as  it  leaves  the  anode  or  reaches  the  kathode),  but  diffuses 
widely  through  the  body,  seeking  the  paths  of  least  resistance.  Thus  it  is  impos- 
sible to  get  pure  anodic  or  kathodic  effects.  If  the  anode  is  applied  over  the  nerve, 
the  current  enters  by  a  series  of  points  (polar  zone),  and  leaves  by  a  second  series 
of  points  (peripolar  zone).  The  second  series  of  points  is  very  close  to  the  first,  as 
the  current  leaves  the  nerve  as  soon  as  possible,  seeking  less  resistant  paths.  The 
polar  zone  will  be  in  the  condition  of  anelectrotonus,  the  peripolar  in  that  of 
katelectrotonus,  so  that  although  the  former  effect  will  predominate,  the  points  being 
more  concentrated,  the  latter  effect  may  prevent  a  pure  anelectrotonic  effect 
being  observed  (fig.  174). 

PflUger's  law  of  contraction  according  to  which  excitation  occurs  at  the  kathode 
on  the  make  of  a  constant  current,  and  at  the  anode  on  the  break,  holds  good  for 
all  excitable  tissues.  The  excitation  at  the  break  is  probably  really  due  to  the 
make  of  a  polarisation  current  having  its  kathode  at  the  former  anode,  and  is 
therefore  fundamentally  of  the  same  nature  as  the  make  contraction  ;  or,  in  general 


Shin 


FIG.  174. — Electrodes  applied  to  the  skin  over  a  nerve-trunk.     In  A  the  polar  area  is  anelectrotonic, 

and  the  peripolar  katelectrotonic.     The  former  condition,  therefore,   preponderates,  since  the  *» 

current  is  more  concentrated.     In  B  the  conditions  are  reversed,  the  polar  zone  corresponding  here 
to  the  kathode.    (After  Waller.) 

terms,  excitation  occurs  only  at  the  place  where  a  current  leaves  the  excitable 
tissue.  No  doubt  the  effect  is  determined  by  the  electrolytic  changes  occurring  at 
the  point  of  entry  and  exit  of  the  current ;  the  development  of  kat-ions  must  there- 
fore be  the  chemical  change  that  results  in  excitation.  It  is  difficult  to  imagine  that 
in  a  degenerated  muscle  there  should  be  a  reversal  of  such  a  fundamental  law,  and 
that  excitation  should  be  associated  with  the  development  of  an-ions.  Yet  this  is 
supposed  to  occur  in  the  qualitative  change  known  as  the  **  reaction  of  degenera- 
tion. "  Page  May  investigated  this  question  afresh,  and  found  that  the  reversal 
of  the  law  is  only  apparent,  not  real,  and  is  due  to  the  imperfect  method  which 
clinical  observers  must  necessarily  employ  when  testing  the  electrical  reaction  of 
muscles  through  the  skin.  By  the  use  of  appropriate  electrodes  on  the  degenerated 
muscles  of  animals,  it  is  possible  to  detect  the  source  of  error.  Let  us  substitute  a 
muscle  for  a  nerve  in  the  diagrams  of  fig.  174  ;  the  current  enters  a  few  fibres  at 
the  anode,  then  spreads  in  all  directions,  and  leaves  the  muscle  by  a  number  of 
diffused  kathodic  points.  If  the  muscle  is  degenerated,  its  excitability  is  high, 
and  the  ready  response  at  the  anode  when  the  current  is  made  does  not  really  occur 
at  the  actual  anode,  but  in  the  neighbouring  and  more  widespread  peripolar 
kathodes.  In  other  words,  degenerated  muscle  obeys  the  general  law  of  excitable 
tissues,  and  excitation  occurs  only  at  the  situation  where  the  current  leaves  'the 
muscle.  At  the  actual  anode  there  is  relaxation  or  absence  of  effect ;  this  is 
obviously  not  observable  through  the  human  skin  because  the  change  is  very 
limited  in  extent ;  it  can  be  actually  seen  in  the  exposed  muscles  of  an  animal. 


CHAPTEE    XVI 

NERVE-CENTRES 

THE  nerve-centres  consist  of  the  brain  and  spinal  cord;  they  are 
characterised  by  containing  nerve-cells,  from  which  the  nerve-fibres 
of  the  nerves  originate.  Small  collections  of  nerve-cells  are  found 
also  in  portions  of  the  peripheral  nervous  system,  where  they  are 
called  ganglia.  The  spinal  ganglia  on  the  posterior  roots  of  the 
spinal  nerves,  and  the  sympathetic  ganglia  are  instances  of  these. 

The  general  arrangement  of  the  cerebro-spinal  axis  is  given  in 
the  accompanying  diagram.  The  nerves  which  take  origin  from  the 
brain  are  called  cranial  nerves ;  there  are  twelve  pairs  of  these ;  some 
of  them,  such  as  the  olfactory,  optic,  and  auditory  nerves,  are  nerves 
of  special  sense ;  others  supply  the  region  of  the  head  with  motor 
and  sensory  fibres.  One  pair  (the  tenth),  called  the  pneumogastric 
or  vagus  nerves,  are  mainly  distributed  to  the  viscera  of  the  thorax 
and  abdomen,  and  a  part  of  another  pair  (the  eleventh),  called  the 
spinal  accessory  nerves,  unites  with  the  vagus  prior  to  such  distribu- 
tion. We  shall  in  our  subsequent  study  of  the  heart,  lungs,  stomach, 
and  other  organs  have  frequently  to  allude  to  these  nerves.  The 
first  two  pairs  of  cranial  nerves  (the  olfactory  and  the  optic)  arise 
from  the  cerebrum.  The  remaining  ten  pairs  are  connected  with  the 
district  of  grey  matter  called  the  floor  of  the  fourth  ventricle  or  its 
immediate  neighbourhood ;  this  tract  of  grey  matter  is  situated  at 
the  lower  part  of  the  brain  where  it  joins  the  spinal  cord;  this 
portion  of  the  brain  is  called  the  Bulb  or  Medulla  dblongata. 

The  spinal  nerves  are  arranged  in  pairs,  31  in  number.  Their 
general  structure  and  functions  we  have  already  studied  (pp.  155-158). 

The  more  intimate  structure  of  the  brain  and  spinal  cord  we  shall 
consider  at  length  in  subsequent  chapters.  For  the  present  we  shall 
deal  with  some  of  the  general  aspects  of  the  nerve-centres,  both  as 
regards  structure  and  function. 

The  brain  and  spinal  cord  consist  of  two  kinds  of  tissue,  easily 
distinguishable  by  the  naked  eye.  They  are  called  respectively  white 
matter  and  grey  matter. 

180 


CH.  XVI.] 


WHITE  AND   OBEY   MATTER 


181 


White  matter  is  composed 
in  structure  from  the  medul- 
lated    fibres    of    nerve    by 
having  no  primitive  sheath 
(neurilemma). 

Grey  matter  is  the  true 
central  material  so  far  as  re- 
gards function;  that  is  to 
say,  it  is  the  part  which 
receives  and  sends  out 
nervous  impulses;  it  is 
characterised  by  containing 
the  bodies  of  the  nerve- 
cells. 

In  the  brain  the  grey 
matter  is  chiefly  situated 
on  the  surface,  forming 
what  is  called  the  cortex; 
the  white  matter  and  cer- 
tain subsidiary  masses  of 
grey  matter  are  in  the 
interior. 

In  the  spinal  cord,  the 
grey  matter  is  in  the  in- 
terior, the  white  matter 
outside. 

In  both  grey  and  white 
matter  the  nerve-cells  and 
nerve-fibres  are  supported 
by  a  peculiar  tissue  which 
is  called  neuroglia.  It  is 
composed  of  cells  and  fibres, 
the  latter  being  prolonged 
from  the  cells.  Some  of  the 
fibres  are  radially  arranged. 
They  start  from  the  outer 
ends  of  the  ciliated  epithe- 
lium cells  that  line  the 
central  canal  of  the  spinal 
cord  and  the  ventricles  of 
the  brain,  and  diverge  con- 
stantly branching  towards 
the  surface  of  the  organ, 
where  they  end  by  slight 
enlargements  attached  to 


of  medullated  nerve-fibres,  which  differ 


FIG.  175. — View  of  the  cerebro-spinal  axis  of  the  nervous 
system.  The  right  half  of  the  cranium  and  trunk  of 
the  body  has  been  removed  by  a  vertical  section ;  the 
membranes  of  the  brain  and  spinal  cord  have  also  been 
removed,  and  the  roots  and  first  part  of  the  fifth  and 
ninth  cranial,  and  of  all  the  spinal  nerves  of  the  right 
side,  have  been  dissected  out  and  laid  separately  on  the 
wall  of  the  skull  and  on  the  several  vertebrae  opposite 
to  the  place  of  their  natural  exit  from  the  cranio-spinal 
cavity.  (After  Bourgery.) 


182  NEKVE-CENTRES  [CH.  XYT. 

the  pia  mater.  The  other  fibres  of  the  tissue  are  cell  processes  of 
the  neuroglia  or  glia  cells  proper,  or  spider  cells  as  they  are  some- 
times termed  (see  fig.  176). 

Neuroglia  is  thus  a  connective  tissue  in  function,  but  it  is  not 
one  in  origin.  Like  the  rest  of  the  nervous  system,  it  originates 
from  the  outermost  layer  of  the  embryo,  the  epiblast.  All  true 
connective  tissues  are  mesoblastic. 

Chemically,  it  is  very  different  from  connective  tissues.     It  con- 


Fio.  176.— Branched  neuroglia-cell.    (After  Stohr.) 

sists  of  an  insoluble  protein  material  called  neuro-keratin,  or  nerve- 
horn,  similar  to  the  horny  substance,  keratin,  which  is  found  in  the 
surface  layers  of  the  epidermis. 

Structure  of  Nerve-Cells. 

Nerve-cells  differ  a  good  deal  both  in  shape  and  size. 

In  the  early  embryonic  condition,  the  future  nerve-cell  is  a  small 
nucleated  mass  of  protoplasm  without  processes.  As  development 
progresses  branches  grow,  and  by  this  means  it  is  brought  into  con- 
tact with  the  branches  of  other  nerve-cells.  When  the  nerve-cells 
degenerate,  as  they  do  in  some  cases  of  brain  and  cord  disease,  there 
is  a  reversal  of  this  process ;  just  as  in  a  dying  tree  the  terminal 
branches,  those  most  distant  from  the  seat  of  nutrition,  are  the  first 
to  wither,  so  it  is  in  the  degenerating  nerve-cell.  If  one  traces  the 
structure  of  nerve-cells  throughout  the  zoological  series,  there  is  also 
seen  an  increase  in  their  complexity,  and  the  number  of  points  of 
contact,  produced  by  an  increase  in  the  number  and  complexity  of  the 
branches,  multiplies  (fig.  177). 


CIL  XYL] 


NERVE-CELLS 


183 


The  simplest  nerve-cells  known  are  termed  bipolar.  In  the  lower 
animals  the  two  processes  come  off  from  the  opposite  ends  of  the 
cells ;  the  cell,  in  other  words,  appears  as  a  nucleated  enlargement  on 
the  course  of  a  nerve-fibre.  Fig.  178  (A)  shows  one  of  these  nerve- 
cells  from  the  Gasserian  ganglion  of  the  pike.  The  cells  of  the 
Gasserian  and  spinal  ganglia  in  the  mammalian  embryo  are  also 
bipolar,  but  as  development  progresses,  the  two  branches  become 
fused  for  a  considerable  distance,  so  that  in  the  fully  formed  animal 
each  cell  appears  to  be  unipolar.  This  is  shown  in  a  more  diagram- 
matic way  in  fig.  159,  p.  155.  The  bifurcation  of  the  nerve-fibre  is 


Fio.  177.— Diagram  after  Ramon  y  Cajal  to  show  the  ontogenetic  (or  embryological)  and  phylogenetic 
(i.e.  in  the  animal  series)  development  of  a  neuron.  A,  cerebral  cell  of  frog ;  B,  newt ;  C,  mouse  ; 
D,  mam.  As  the  place  in  the  zoological  series  rises,  the  neuron  increases  in  complexity  and  in  the 
number  of  points  of  contact ;  this  is  produced  partly  by  an  increase  of  the  dendrons,  partly  by  an 
increase  in  the  side  branches  or  collaterals  of  the  axon.  a,  b,  c,  d,  e,  show  the  early  stages  in  the 
development  of  a  similar  cell  in  the  human  embryo  ;  the  first  branch  of  the  cell  to  appear  (in  a)  is 
the  axon  ;  the  dendrons  are  later  outgrowths.  The  reversal  of  this  process  takes  place  in  primary 
degeneration. 

spoken  of  as  a  T-shaped  junction.  As  will  be  seen  in  fig.  178  (C), 
the  nerve  process  has  a  convoluted  course  on  the  surface  of  the  cell 
before  it  bifurcates.  In  these  ganglia  it  should  be  also  noted  that 
each  cell  is  enclosed  within  a  connective  tissue  sheath,  and  the  nuclei 
seen  are  those  of  the  connective  tissue  corpuscles. 

The  majority  of  nerve-cells  found  in  the  body  are  multipolar. 
Here  the  cell  becomes  angular  or  stellate.  Fig.  179  shows  the  usual 
form  of  cell  present  in  sympathetic  ganglia.  From  the  angles  of  the 
cell,  branches  originate ;  the  majority  of  these  branches  divide  and 
subdivide  until  each  ends  in  an  arborescence  of  fine  twigs  or  fibrils ; 


184 


NERVE-CENTRES 


[CH.  XVI. 


but  one  process,  and  one  process  only,  of  each  cell  becomes  the  axis 
cylinder  of  a  nerve-fibre. 

Passing  next  to  the  central  nervous  system,  we  here  again  find 
the  multipolar  cell  is  the  principal  kind  present. 


N.S. 


FIG.  178.— Bipolar  nerve-cells.  A.  From  the  Gasserian  ganglion  of  the  pike  (after  Bidder).  B.  From  a 
spinal  ganglion  of  a  4k  weeks'  human  embryo  (after  His).  C.  Adult  condition  of  the  mammalian 
spinal  ganglion  cell :  N.  S.  nucleated  sheath  ;  only  the  nuclei  seen  in  profile  are  represented.  T.  is 
the  T-shaped  junction  (after  Retzius). 

Fig.  180  shows  one  of  the  typical  multipolar  cells  of  the 
spinal  cord.  Here  again,  only  one  process  (a)  becomes  the  axis 
cylinder  of  a  nerve-fibre,  and  the  others  break  up  into  arborisa- 
tions of  fibrils.  The  cells  have  a  finely  fibrillar  structure,  and  the 
fibrils  can  be  traced  into  the  axis  cylinder  process  and  the  other 
branches  of  the  cell.  Between  the  fibrils  the  protoplasm  of  the  cell 
contains  a  number  of  angular  or  spindle-shaped  masses,  which  have 
a  great  affinity  for  basic  aniline  dyes  like  methylene  blue.  They  are 
known  as  Nissl's  granules.  These  nerve-cells  often  contain,  especi- 
ally in  the  adult,  granules  of  pigment,  usually  yellow,  the  nature  of 
which  has  not  been  determined. 


CH.  XVI.] 


NEHVE-CELLS 


185 


In  preparations  made  by  Golgi's  chromate  of  silver  method,  the 
cells  and  their  processes  are  stained  an  intense  black  by  a  deposit  of 


•FIG.  179. — An  isolated  sympathetic  ganglion  cell  of  man,  showing  sheath  with  nucleated  cell  lining,  B. 
A.  Ganglion  cell,  with  nucleus  and  nucleolus.  C.  Branched  process.  D.  Axis  cylinder  process 
(Key  and  Ketzius.)  x  750. 

silver.     The  various  structures  in  the  cells  (nucleus,  granules,  fibrils, 
etc.),  are  not  visible  in  such  preparations,  but  the  great  advantage  of 


FIG.  180. — Multipolar  nerve-cell  from  anterior  horn  of  spinal  cord ;  a,  axis  cylinder  process. 

Schultze.) 


(Max 


186 


NERVE-CENTRES 


[CH.  XYI. 


the  method  is  that  it  enables  one  to  follow  the  branches  to  their  finest 
ramifications.     It  is  thus  found  that  the  axis  cylinder  process  is  not 

unbranched,  as  represented  in 
fig.  180,  but  invariably  gives  off 
side-branches,  which  are  called 
collaterals ;  these  pass  into  the 
adjacent  nerve- tissue.  The  axis 
cylinder  then  acquires  the 
sheaths,  and  thus  is  converted 
into  a  nerve-fibre.  This  nerve- 
fibre  sometimes,  as  in  the  nerve- 
centres  after  a  more  or  less 
extended  course,  breaks  up  into 
a  terminal  arborescence  envelop- 
ing other  nerve-cells ;  the  col- 
laterals also  terminate  in  a 
similar  way.  The  longest  type 
of  axis  cylinder  is  that  which 


FIG.  181. — Pyramidal  cell  of  human  cerebral  cortex. 
Golgi's  method. 

passes  away  from  the  nerve-centre, 
and  gets  bound  up  with  other 
similarly  sheathed  axis  cylinders 
to  form  a  nerve;  but  all  ulti- 
mately terminate  in  an  arbor- 
escence of  fibrils  in  various 
end  -  organs  (end-plates,  muscle 
spindles,  etc.). 


H 


FIG.  182.— Cerebral  cortex  of  mammal,  prepared 
by  Golgi's  method.  A,  B,  C,  D,  F,  nerve- 
cells;  E,  neuroglia-cell.  (Ramon  y  Cajal.) 


In  the  grey  matter  of  the  cerebrum  the  nerve-cells  are  various  in 
shape  and  size,  but  the  most  characteristic  cells  are  pyramidal  in 


CH.  XVI.]  NERVE-CELLS  187 

shape.  They  are  especially  large  and  numerous  in  what  are  called 
the  motor  areas  of  the  brain.  The  apex  of  the  cell  is  directed  to  the 
surface ;  the  apical  process  is  long  and  tapering,  and  finally  breaks 
up  into  fibrils  that  lie  parallel  to  the  surface  of  the  brain  (tangential 
fibres).  From  the  lower  angles  and  other  parts  branching  processes 
originate ;  the  axis  cylinder  comes  off  from  the  base  of  the  pyramid. 
(See  figs.  181,  182). 

The  grey  matter  of  the  cerebellum  contains  a  large  number  of 
small  nerve-cells,  and  one  layer  of  large  cells.  These  are  flask-shaped, 
and  are  called  the  cells  of  Purkinje.  The  neck  of  the  flask  breaks  up 


Axon 


FIG.  183. — Cell  of  Purkinje  from  the  human  cerebellum.     Golgi's  method. 
(After  Szymonowicz.) 

into  branches,  and  the  axis  cylinder  process  comes  off  from  the  base 
of  the  flask  (fig.  183). 

The  whole  nervous  system  consists  of  nerve-cells  and  their 
branches,  supported  by  neuroglia  in  the  central  nervous  system,  and 
by  connective  tissue  in  the  nerves.  Some  of  the  processes  of  a 
nerve-cell  break  up  almost  immediately  into  smaller  branches  ending 
in  arborescences  of  fine  twigs ;  these  branches,  which  used  to  be 
called  protoplasmic  processes,  are  now  termed  dendrons.  One  branch 
becomes  the  long  axis  cylinder  of  a  nerve-fibre,  but  it  also  ultimately 
terminates  in  an  arborisation ;  it  is  called  the  axis  cylinder  process, 
or,  more  briefly,  the  axon.  The  term  neuron  or  neurone  is  applied  to 


188 


NERVE-CENTRES 


[CH.  XVI. 


the  complete  nerve-unit,  that  is,  the  body  of  the  cell,  and  all  its 
branches.  The  fibrils  of  the  axon  may  be  traced  through  the  body 
of  the  cell  from  the  dendrons. 

The  next  idea  which  it  is  necessary  to  grasp  is,  that  each  nerve- 
unit  (cell  plus  branches  of  both  kinds)  is  anatomically  independent 
of  every  other  nerve-unit.  There  is  no  true  anastomosis  of  the 
branches  from  one  nerve-cell  with  those  of  another ;  the  arborisations 
interlace  and  intermingle,  and  nerve  impulses  are  transmitted  from 
one  nerve-unit  to  another,  through  contiguous,  but  not  through  con- 
tinuous structures.  A  convenient  expression  for  the  intermingling 
of  arborisations  is  synapse  (literally,  a  clasping). 

Fig.  184  is  a  diagram  of  the  nervous  path  in  a  spinal  reflex  action. 
Excitation  occurs  at  S,  the  skin  or  other  sensory  surface,  and  the 


A.C.C 


FIG.  184.— Reflex  action. 

impulse  is  transmitted  by  the  sensory  nerve-fibre  to  the  central 
nervous  system.  It  does  not  become  anatomically  connected  to  any 
of  the  cells  of  the  central  nervous  system.  The  only  cell-body  in 
actual  continuity  with  the  sensory  nerve-fibre  is  the  one  in  the  spinal 
ganglion  (G)  from  which  it  grew.  On  entering  the  spinal  cord,  the 
main  fibre  conveys  impulses  upwards  which  ultimately  reach  the 
brain,  but  in  the  spinal  cord  it  gives  off  fine  side  branches  or 
collaterals  which  terminate  in  branches  that  arborise  around  one  or 
more  cell  bodies  and  their  dendrons;  these  cells  are  small  ones 
situated  in  the  posterior  cornu  of  the  spinal  grey  matter ;  one  only 
(P.C.C.)  is  shown  in  the  diagram.  The  short  axon  of  this  cell  similarly 
terminates  by  a  synaptic  junction  with  one  or  more  of  the  large 


CH.  XVI.]  SYSTEMS   OF  RELAY  189 

multipolar  cells  of  the  anterior  cornu  of  the  spinal  grey  matter; 
one  of  these  shown  in  the  figure  is  labelled  A.C.C.  This  motor-cell 
is  thus  stirred  up  to  action  and  sends  an  impulse  by  its  axon  to  the 
muscular  fibres  (M)  it  supplies.  Thus  excitation  of  the  skin  will 
cause,  by  this  spinal  reflex  arc,  the  contraction  of  muscles.  In  some 
cases  severe  excitation  will  cause  contraction  of  the  muscles  of  the 
opposite  side  of  the  body  (crossed  reflex) ;  under  such  circumstances 
the  intermediary  neuron  (P.C.C.)  sends  its  axon  to  the  anterior 
horn-cells  of  the  opposite  side.  The  synaptic  junctions  are  naturally 
the  places  which  the  impulse  has  the  greatest  difficulty  in  traversing ; 
and  some  observers  believe  that  at  the  points  of  contact  there  is  a 
kind  of  undifferentiated  interstitial  protoplasm  which  the  impulse 
has  to  get  through. 

This  example  illustrates  a  most  important  general  truth,  namely, 
that  a  nervous  impulse  does  not  necessarily  travel  along  the  same 
nerve-fibre  all  the  way,  but  there  is  what  we  may  term  a  system  of 
relays.  The  nervous  system  is  very  often  compared  to  a  telegraphic 
system  throughout  a  country.  The  telegraph  offices  represent  the 
nerve-centres,  the  afferent  nerve-fibres  correspond  to  the  wires  that 
carry  the  messages  to  the  central  offices,  and  the  efferent  nerve- 
fibres  are  represented  by  the  wires  that  convey  messages  from  the 
central  offices  to  more  or  less  distant  parts  of  the  country.  This 
illustration  will  serve  us  very  well  for  our  present  purpose,  provided 
that  it  is  always  remembered  that  a  nervous  impulse  travels  more 
slowly  than  electricity.  Suppose,  now,  one  wishes  to  send  a  message 
from  the  metropolis,  which  will  represent  the  brain,  to  a  distant 
house,  say  in  the  Highlands  of  Scotland.  There  is  no  wire  straight 
from  London  to  that  house,  but  the  message  ultimately  reaches  the 
house;  one  wire  takes  the  message  to  Edinburgh;  another  wire 
carries  it  on  to  the  telegraph  station  in  the  town  nearest  to  the 
house  in  question ;  and  the  last  part  of  the  journey  is  accomplished 
by  a  messenger  on  foot  or  horseback.  There  are  at  least  two  relays 
on  the  journey. 

"We  may  take  another  illustration  of  this.  Suppose  one  wishes 
to  move  the  arm ;  the  impulse  starts  in  the  nerve-cells  of  the  brain, 
but  there  are  no  fibres  that  go  straight  from  the  brain  to  the 
muscles  of  the  arm.  The  impulse  travels  down  the  spinal  cord,  by 
what  are  called  pyramidal  fibres,  which  form  synapses  with  the 
nerve-cells  of  the  spinal  cord,  and  from  these  cells  fresh  nerve- 
fibres  pass  on  the  impulse  to  the  arm-muscles.  This  is  shown  in 
the  accompanying  diagram  (fig.  185).  The  cell  of  the  cerebral  grey 
matter  is  represented  by  C.C.,  and  its  axon  (pyramidal  fibre)  by 
P.F.  This  passes  into  the  white  matter  of  the  brain,  and  in  the 
medulla  oblongata  it  crosses  over,  and  then  travels  down  the 
opposite  side  of  the  spinal  cord.  It  enters  the  grey  matter  in  the 


190 


NERVE-CENTRES 


[CH.  XVI. 


part  of  the  cord  which  controls  the  arm  movements,  and  terminates 
by  arborising  around  small  cells  at  the  base  of  the  posterior  cornu 

(P.C.C.);  thence  the  im- 
pulse is  transferred  to  the 
large  motor  cells  of  the 
anterior  cornu  (A.C.C.), 
and  the  final  link  in  the 
chain  is  formed  by  the 
motor  nerve-fibres  to  the 
muscular  fibres  (M).  The 
spinal  cord  cells  are  thus 
surrounded  by  arborisa- 
Itions  (synapses),  derived 
not  only  from  the  sensory 
[nerves  but  by  fibres  from 
the  upper  part  of  the 
nervous  system.  We  now 
see  how  it  is  possible  that 
reflex  actions  in  the  cord 
may  be  controlled  by  im- 
pulses from  the  brain. 
[>;f|  The  system  of  relays 
is  still  more  complicated 
in  the  case  of  sensory  im- 
pulses, as  we  shall  see  later 
on;  the  same  is  true  for 
the  motor  path  to  involun 
tary  muscle,  accessory  cell- 
stations  being  situated  in 
the  sympathetic  ganglia. 

We  may  now  return  for 
a  moment  to  the  subject  of 
degeneration.  If  the  nerve- 
fibre  is  cut  off  from  its 
connection  with  the  spinal 
nerve-cell,  the  peripheral 
end  degenerates  as  far  as 
the  muscle. 

Suppose,  now,  the  pyra- 
midal fibre  were  cut  across, 
the  piece  still  attached  to  the  brain-cell  would  remain  in  a  compara- 
tively normal  condition,  but  the  peripheral  end  would  degenerate  as 
far  as  the  next  synapse.  We  can  thus  use  the  degeneration  method 
to  trace  out  tracts  of  nerve-fibres  in  the  white  matter  of  the  central 
nervous  system.  The  histological  change  in  the  fibres  is  here  the  same 


FIG.  185.— Diagram  of  the  neurons  of  the  motor  path 


OIL  XVI.]  LAW   OF  AXIPETAL  CONDUCTION  191 

as  that  already  described  in  the  nerves,  except  that,  as  there  is  no 
primitive  sheath,  there  can  be  no  multiplication  of  its  nuclei;  there 
is  instead  an  overgrowth  of  neuroglia.  Degenerated  tracts  conse- 
quently stain  differently  from  healthy  white  matter,  and  can  by  this 
means  be  easily  detected. 

Another  method  of  research  which  leads  to  the  same  results  as 
the  degeneration  method  is  called  the  embryological  method.  The 
nerve-fibres  which  grow  from  different  groups  of  nerve-cells  become 
fully  developed  at  different  dates,  and  so,  by  examining  brains  and 
cords  of  embryos  of  different  ages,  one  is  able  to  make  out  indivi- 
dual tracts  before  they  have  blended  in  the  general  mass  of  white 
matter. 

We  shall,  however,  return  to  this  subject  when  later  on  we  are 
studying  the  physiology  of  the  central  nervous  system  in  detail. 

The  Law  of  Axipetal  Conduction. 

A  general  law  has  been  laid  down  by  van  Gehuchten  and  Cajal, 
that  all  nerve  impulses  are  axipetal,  that  is,  they  pass  towards  the 
attachment  of  the  axon,  by  which  they  leave  the  body  of  the  cell. 
In  other  words,  the  direction  of  an  impulse  is  towards  the  body  of 
the  cell  in  the  dendrons,  and  away  from  it  in  the  axon.  When  we 
further  consider  that  every  nervous  pathway  is  formed  of  a  chain  of 
cells,  and  that  the  impulse  always  takes  the  "  forward  direction,"  we 
see  that  there  is  what  we  may  compare  to  a  valved  action  which 
permits  the  passage  of  impulses  in  one  direction  only.  The  synapses 
are  the  situations  of  these  so-called  valves. 

On  the  onward  propagation  of  a  nerve  impulse  through  a  chain 
of  neurons,  its  passage  is  delayed  at  each  synapse,  hence  there  is 
additional  "  lost  time  "  at  each  of  these  blocks.  The  relative  number 
of  the  blocks  furnishes  a  key  to  the  differences  found  in  reaction 
time  for  different  reflexes  and  psychical  processes.  This  we  may 
illustrate  by  two  examples,  one  taken  from  the  frog,  the  other  from 
man. 

1.  If  a  frog's  posterior  root  is  stimulated,  the  time  lost  in  the 
spinal  cord  when  the  gastrocnemius  of  the  same  side  contracts  is 
0*008  sec. ;  if  the  opposite  gastrocnemius  contracts,  the  additional 
lost  time  is  0*004  sec.     If  we  assume  that  in  the  latter  case,  two 
extra  synapses  have  to  be  jumped,  the  delay  at  each  is  0*002  sec. 

2.  In  the  case  of  the  eye  and  ear  in  man  the  total  length  of  the 
pathway  to  the  brain  is  approximately  the  same,  and  so  the  reaction 
times  might  be  expected  to  be  equal ;  but  this  is  not  the  case ;  the 
reaction  time  in  response  to  a  sudden  sound  is  0*150  sec.,  in  response 
to  a  sudden  flash  of  light  0*195  sec.     The  greater  delay  in  response 
to  a  visual  stimulus  directly  corresponds  to  the  greater  number  of 


192  NERVE-CENTRES  [CH.  XVI. 

synapses  through  which  it  has  to  travel  (see  later,  on  the  structure 
of  the  visual  and  auditory  mechanisms). 

The  valved  condition  of  nervous  paths  also  explains  another 
difficulty.  We  have  seen  on  p.  160  that  under  certain  circumstances 
a  nervous  impulse  will  travel  in  both  directions  along  a  nerve.  Yet 
when  we  stimulate  the  motor  fibres  in  an  anterior  spinal  root,  the 
only  effect  is  a  contraction  of  muscles ;  there  is  no  effect  propagated 
backwards  in  the  spinal  cord.  No  doubt  a  nervous  impulse  does 
travel  backwards  to  the  anterior  horn  cells,  but  it  is  there  extin- 
guished, it  cannot  jump  the  synapses  backwards,  and  there  is  no 
negative  variation  to  be  detected  in  a  galvanometer  connected  to  the 
pyramidal  tracts  in  the  cord. 

The  law  of  axipetal  conduction  is  no  doubt  true  for  the  majority 
of  neurons.  But  there  is  at  any  rate  one  very  striking  exception, 
namely,  in  the  neurons  of  the  spinal  ganglia;  here  the  impulse 
passes  to  the  body  of  the  cell  by  one  axon  from  the  periphery,  and 
away  from  it  to  the  spinal  cord  by  the  other.  To  say,  as  some  do, 
that  the  peripheral  process  is  really  a  dendron  because  it  conducts 
impulses  centripetally,  is  simply  arguing  in  a  circle. 

The  Significance  of  Nissl's  Granules. 

If  portions  of  the  brain  or  spinal  cord  are  fixed  in  absolute  alcohol, 
and  sections  obtained  from  the  hardened  pieces  are  stained  by  means 
of  methylene  blue,  the  nerve-cells  exhibit  a  characteristic  appearance. 
The  nucleus  and  nucleolus  take  up  the  blue  stain,  but  the  total 
amount  of  chromatin  present  in  the  nucleus  is  not  large,  except  in 
embryonic  nerve-cells ;  throughout  the  cell  body  a  number  of  angular- 
shaped  masses,  which  are  termed  Nissl's  granules,  are  also  stained 
blue.  These  extend  some  distance  into  the  dendrons,  but  not  into 
the  axon.  The  substance  of  which  they  are  composed  is  termed 
chromatoplasm,  or  chromopJiilic  material.  The  existence  of  granules 
in  cells  which  have  an  affinity  for  basic  dyes  such  as  methylene  blue 
is  not  at  all  common ;  the  granules  in  the  majority  of  the  white  blood- 
corpuscles,  for  instance,  have  an  affinity  for  acid  dyes.  Micro- 
chemical  methods  have  shown  that  the  main  constituent  of  the  Nissl 
granules  is  an  iron-containing  nucleo-protein.  The  name  kineto- 
plasm  has  been  given  to  it  by  Marinesco  in  order  to  express  the  idea 
that  it  forms  a  source  of  energy  to  the  cell.  It  can  hardly  be  denied 
that  the  substance  of  which  the  granules  are  composed,  forming  as 
it  does  so  large  a  proportion  of  the  cell-contents,  and  made  of  a 
material  in  which  nuclein  forms  an  important  constituent,  is  intimately 
related  to  the  nutritional  condition  of  the  neuron.  Some  have  even 
compared  it  to  the  granular  material  which  is  present  in  secreting 
cells;  in  these  cells  before  secretion  occurs,  the  granules  accumulate, 


CH.  XVI.] 


NISSL'S    GRANULES 


193 


and  during  the  act  of  secretion  they  are  discharged  and  converted 
into  constituents  of  the  secretion.  It  is  stated  by  some  observers 
that  the  Nissl  granules  are  used  up  during  the  discharge  of  energy 
from  nerve-cells,  and  it  certainly  is  the  case  that  if  the  cells  are 
examined  after  an  epileptic  fit,  in  which  there  has  been  a  very  massive 
discharge  of  impulses,  the  Nissl  granules  have  disappeared,  or  at 
least  broken  up  into  fine  dust-like  particles,  so  that  the  cell  presents 
a  more  uniform  blue  staining.  This  is  called  chromatolysis  (see 
fig.  186).  It  is,  however,  doubtful  whether  this  is  due  to  a  transfor- 
mation associated  with  intense  activity,  or  whether  it  may  not  be 


Fto.  186. — Nissl's  granules.  A.  Normal  pyramidal  cell  of  human  cerebral  cortex.  B.  Swollen  rede* 
matous  pyramidal  cell  from  a  case  of  status  epilepticus.  Notice  diffuse  staining,  and  absence  of 
Nissl's  granules ;  the  nucleus  is  enlarged  and  eccentric.  The  lymph  space  around  the  cell  is 
dilated.  C.  Pyramidal  cell  of  dog  after  ligature  of  vessels  going  to  brain  and  consequent  anaemia. 
Notice  great  swelling  of  the  nucleus,  and  advanced  chromatolysis,  most  marked  at  the  periphery 
of  the  cell.  700  diameters.  (After  Mott.) 

caused  by  venosity  of  the  blood.  The  cells  are  very  sensitive  to 
altered  vascular  conditions ;  ansemia,  for  instance,  produces  a  similar 
change  accompanied  with  swelling  of  the  cell,  and  swelling  and  in 
extreme  cases  extrusion  of  the  nucleus. 

The  most  convincing  observations  in  reference  to  the  influence  of 
fatigue  in  producing  chromatolysis  have  been  made  on  bees ;  their 
nerve-cells  are  rich  in  chromophilic  material  when  they  are  about 
to  leave  the  hive  in  the  morning.  In  the  evening,  after  a  hard  day's 
work,  this  material  is  much  reduced  in  quantity. 

By  this  sensitive  method  neurologists  have  been  able  to  identify 
changes  in  the  cells  which  could  not  be  detected  by  the  previous 
methods  of  staining.  Thus  the  cells  have  been  examined  in  various 
diseases,  or  after  being  subjected  to  the  action  of  certain  poisons,  and 

N 


194  NERVE-CENTRES  [CH.  XVI. 

valuable  results  have  been  obtained.  We  will,  however,  be  content 
with  alluding  to  only  one  pathological  condition,  namely,  that  pro- 
duced by  extremely  high  fever  (hyperpyrexia) ;  in  this  condition 
chromatolysis  is  very  marked  and  is  produced  by  the  coagulation  of 
the  proteins  of  the  cell-protoplasm  by  the  high  temperature. 

The  question  has  arisen  whether  the  Nissl  granules  are  present 
as  such  in  the  living  cell,  or  whether  they  are  artifacts  produced  by 
the  fixative  action  of  strong  alcohol.  But,  whichever  view  is  correct, 
the  method  is  a  valuable  one,  and  Nissl's  views  on  this  question 
appear  to  be  indisputable :  they  are  briefly  as  follows : — Healthy  cells 
fixed  and  stainejj  in  a  constant  manner  will  appear  the  same  under 
constant  optical  conditions,  and  the  appearances  then  seen  form  the 
equivalent  of  such  healthy  cells  during  life.  It  follows  that  if  the 
cells  prepared  by  the  same  method  and  examined  under  the  same 
conditions  show  a  difference  from  the  equivalent  or  symbol  of  healthy 
cells,  the  difference  is  the  measure  of  some  change  that  has  occurred 
during  life.  The  view  most  generally  held  is  that  the  granules  are 
artifacts,  and  that  the  actual  Mssl  substance  in  the  living  nerve-cell 
is  a  fluid  plasm  of  rich  nutritive  value  to  the  fibrils. 

Chromatolysis  alone  is  not  indicative  of  cell  destruction,  and  a 
cell  may  recover  its  function  afterwards.  The  integrity  of  the 
nucleus  and  of  the  fibrils  between  which  the  Nissl  substance  lies  is 
much  more  important  to  the  actual  vitality  of  the  cell. 

When  a  nerve-fibre  is  cut  across,  the  distal  segment  undergoes 
Wallerian  degeneration ;  this  is  an  acute  change.  But  the  nerve-cell 
and  the  piece  of  the  nerve-fibre  still  attached  to  it  do  not  remain  un- 
affected. If  regeneration  of  the  fibre,  and  restoration  of  function 
takes  place,  no  change  is  observable.  But  if  regeneration  does  not 
occur  (and  it  never  takes  place  in  the  central  nervous  system),  the 
cell  and  its  processes  undergo  a  slow  chronic  wasting ;  one  of  the 
earliest  signs  of  this  disuse  atrophy  is  chromatolysis. 

Classification  of  Neurons  according  to  their  Function. 

In  addition  to  the  anatomical  classification  of  the  nerve-cells 
already  given,  they  may  be  grouped  into  four  chief  classes  on  a 
physiological  basis : — 

1.  Afferent  neurons. 

2.  Efferent  neurons. 

3.  Intermediary  neurons. 

4.  Distributing  neurons. 

1.  Afferent  neurons. — Originally  the  cell  bodies  are  situated  at  the 
periphery,  and  are  connected  with  a  process  or  afferent  fibre  which 
passes  to  and  arborises  among  the  nerve-cells  of  the  central  nervous 


CH.  xn.] 


CLASSIFICATION   OF  NERVE-CELLS 


195 


system.     This  primitive  condition  is  well  seen  in  the  earthworm,  and 
persists  in  the  olfactory  cells  of  all  vertebrates. 

As  evolution  progresses,  the  peripheral  cell  sinks  below  the  in- 
tegument, leaving  a  process  at  the  surface ;  this  is  seen  in  the  worm 
Nereis  (see  fig.  187).  Ultimately  in  the  vertebrates  the  body  of  the 


Earth-worm 


Nereis 


Vertebrate 


FIG.  187.— Diagram  to  illustrate  the  primitive  conditions  of  the  afferent  nerve-cell,  and  the  manner  in 
which  it  becomes  altered  in  the  process  of  evolution.  (After  Retzius.)  I,  integument ;  C,  central 
nervous  system  ;  the  arrows  show  the  direction  in  which  the  impulse  passes. 

cell  approaches  close  to  the  central  nervous  system,  in  the  spinal 
ganglion  of  the  posterior  root,  and  the  peripheral  sensory  nerve-fibre 
is  correspondingly  longer. 

The  afferent  neurons  such  as  those  of  the  spinal  ganglia  and 
the  corresponding  ganglia  of  the  cranial  nerves,  are  peculiar  in 
possessing  no  dendrons. 

2.  Efferent  neurons. — The  anterior  horn-cells  of  the  spinal  cord 
are  instances  of  these ;  their  axons  go  directly  to  muscle  fibres. 

3.  Intermediary  neurons. — These  receive  impulses  from  afferent 
cells,  and  transmit  them  either  directly  or  indirectly  through  other 
intermediary  cells  to  efferent  cells.     The  majority  of  the  cells  of  the 
brain  and  cord  come  under  this  heading ;  they  serve  the  purposes  of 
association    and    coordination,   and   thus    their    activity   underlies 
psychical  phenomena. 

4.  Distributing  neurons. — These  are  the  cells  of  the  sympathetic 
ganglia ;  they  are  situated  outside  the  central  nervous  system ;  they 
receive  impulses  from  efferent  cells  in  the  central  nervous  system, 
and  distribute  them  to  involuntary  muscles  and  secreting  glands. 


CHAPTEE   XVII 

THE  AUTONOMIC   NERVOUS   SYSTEM 

ALLUSION  has  frequently  been  made  in  the  foregoing  chapters  to 
sympathetic  nerves.  These  nerves  govern  the  processes  in  the  body 
over  which  we  have  no  voluntary  control.  They  innervate  cardiac 
muscle,  the  plain  muscle  in  the  walls  of  blood-vessels,  and  in  the 
walls  of  other  contractile  viscera  such  as  the  stomach  and  intestine, 
the  bladder,  and  the  organs  of  generation.  Secretory  nerve-fibres 
also  come  into  the  same  category.  In  the  chapters  which  im- 
mediately follow  this  one,  we  shall  be  studying  such  organs,  organs 
which  carry  on  the  vegetative  functions  of  life  as  it  was  formerly  the 
custom  to  call  them.  It  is  therefore  desirable  that,  at  the  outset,  we 
should  obtain  some  general  idea  of  the  nervous  mechanism  involved 
in  controlling  and  regulating  these  functions. 

The  sympathetic  system  proper  consists  of  a  chain  of  ganglia  or 
collections  of  nerve-cells,  situated  on  each  side  of  the  vertebral 
column.  These  ganglia  correspond  roughly  with  the  spinal  seg- 
ments; the  uppermost  is  called  the  superior  cervical  ganglion,  and  the 
next  the  inferior  cervical  ganglion  ;  these  are  the  only  two  ganglia  in 
the  cervical  region  in  the  dog ;  in  man  there  is  a  middle  cervical 
ganglion  in  addition.  The  inferior  cervical  ganglion  is  connected  to 
the  first  thoracic  ganglion  (a  large  ganglion  sometimes  called  the 
ganglion  stellatum)  by  fibres,  some  of  which  go  in  front  of,  and  others 
behind  the  subclavian  artery;  this  ring  around  the  artery  is  called 
the  annulus  of  Vieussens ;  after  this  the  correspondence  of  the 
ganglia  to  the  spinal  nerve  roots  is  more  exact,  and  we  finally  reach 
the  ganglion  at  the  end  of  the  chain,  the  ganglion  coccygeum. 

All  these  ganglia  (with  the  possible  exception  in  some  animals  of 
the  inferior  cervical  ganglion)  send  bundles  of  nerve-fibres  to  the 
spinal  nerves,  and  the  communicating  strands  between  the  ganglia 
and  the  spinal  nerves  are  termed  the  rami  communicantes.  The 
rami  communicantes  are  divided  into  white  and  grey.  The  white 
rami  consist  of  medullated  fibres  of  small  diameter ;  the  grey  rami 
consist  mainly  of  non-medullated  nerve-fibres. 

The  sympathetic  chain,  then,  is  a  system  of  ganglia  longitudinally 

196 


CH.  XVII.]  THE   AUTONOMIC   NERVOUS   SYSTEM  197 

arranged,  and  these  ganglia  are  called  the  vertebral  or  the  lateral 
ganglia. 

In  connection  with  the  lateral  chain  are  other  outlying  ganglia, 
such  as  the  semilunar  ganglion,  from  which  the  coeliac  plexus  takes 
origin ;  the  superior  mesenteric  ganglion,  and  the  inferior  mesenteric 
ganglion,  from  which  the  hypogastric  nerve  takes  origin.  These 
outlying  ganglia  are  called  the  collateral  or  the  prevertebral  ganglia. 
These  differ  from  the  lateral  ganglia  in  not  sending  any  fibres  back 
to  the  spinal  nerves;  their  fibres  pass  onwards  to  the  thoracic, 
abdominal,  and  pelvic  viscera. 

Finally,  there  are  ganglia  situated  in  the  walls  of  the  organs 
themselves,  as,  for  instance,  those  in  the  heart  wall,  and  those  in  the 
plexuses  of  the  wall  of  the  alimentary  canal  (the  plexuses  of 
Auerbach  and  of  Meissner).  By  some,  these  ganglia  are  included 
with  the  collateral  ganglia,  but  it  appears  better  for  descriptive 
purposes  to  speak  of  them  as  Gaskell  does,  as  a  third  group,  and 
name  them  the  terminal  ganglia. 

The  sympathetic  system  thus  consists  of  three  sets  of  ganglia 
with  strands  connecting  them  together,  and  all  come  into  ultimate 
connection  with  fibres  which  leave  the  spinal  cord. 

There  is,  however,  another  set  of  ganglia  which  are  related 
anatomically  in  a  similar  way  to  some  of  the  cranial  nerves,  and 
physiologically  with  the  involuntary  muscles  and  glands  in  the  head 
region  as  well  as  with  some  of  the  thoracic  and  abdominal  organs. 
Thus  we  have  the  ciliary  ganglion  in  connection  with  the  third 
cranial  nerve;  then  there  are  such  ganglia  as  the  spheno-palatine, 
otic,  and  submaxillary,  in  connection  with  other  cranial  nerves. 

It  has  been  considered  wise  not  to  extend  the  terra  sympathetic 
to  these,  but  to  include  both  them  and  the  sympathetic  system  under 
one  common  term,  and  Langley's  suggestion  that  this  word  should  be 
autonomic  has  been  very  generally  adopted.  The  word  indicates 
that  they  possess  a  certain  power  of  self-government,  and  are  to 
some  extent,  at  any  rate,  independent  of  the  central  nervous  system. 

The  impulses  that  pass  to  the  involuntary  musculature  of  the 
body  arise  in  the  central  nervous  system,  and  travel  to  the  ganglia 
of  the  autonomic  system  by  means  of  fine  medullated  nerve-fibres ; 
the  diameter  of  these  fibres  varies  from  1-8  to  3-6  /*;  the  fibres 
therefore  contrast  with  the  motor  fibres  which  pass  to  voluntary 
muscles;  the  diameter  of  these  being  14  to  19  /x  (see  fig.  95,  p.  77). 
There  is  a  further  contrast  in  the  two  cases;  the  motor  fibres  to 
voluntary  muscles  pass  uninterruptedly  from  the  brain  or  cord  until 
they  terminate  in  the  end-plates  of  the  voluntary  muscles.  The 
autonomic  fibres,  on  the  other  hand,  terminate  by  arborising  around 
cells  in  one  or  other  of  the  autonomic  ganglia,  and  from  the  ganglion 
cells  a  fresh  relay  of  nerve-fibres  carries  on  the  impulse  to  the 


198  THE   AUTONOMIC   NERVOUS   SYSTEM  [CH.  XYII. 

involuntary  muscles.  There  is  thus  an  extra  cell-station  or  synaptic 
junction  outside  the  central  nervous  system  altogether.  The 
autonomic  path,  in  other  words,  consists  of  two  neurons ;  one  from 
the  central  nervous  system  to  the  ganglion,  and  a  second  from  the 
ganglion  to  the  peripheral  tissue.  The  first  axon  is  termed  the  pre- 
ganglionic  fibre;  the  second,  the  post-ganglionic  fibre.  The  pre- 
ganglionic  fibres  are  fine  medullated  ones,  and  the  post-ganglionic 
fibres  are  usually  non-medullated,  but  there  are  exceptions  to  this 
rule. 

The  small  medullated  or  pre-ganglionic  fibres  arise  from  the 
following  four  regions  of  the  central  nervous  system. 

1.  From  the  mid-brain,  issuing  therefrom  by  the  third  cranial 
nerve  (motor  oculi). 

2.  From  the  medulla  oblongata,  issuing  therefrom  in  the  seventh 
(facial),  ninth  (glosso-pharyngeal),  tenth  (vagus),  and  eleventh  (spinal 
accessory)  nerves. 

3.  From  the  thoracic  region  of  the  spinal  cord,  issuing  therefrom 
in  the  anterior  roots  of  the  spinal  nerves  and  passing  from  these  by 
the  white  rami  communicantes  to  the  sympathetic  ganglia.     These 
occur  in   all  the  nerves  from  the  first   or  second  thoracic,  as  far 
down  as  the  second,  third,  or  fourth  lumbar  nerves. 

4.  From  the  sacral  region  of  the  spinal  cord,  issuing  therefrom  by 
the  anterior  roots  of  the  second,  third,  and  fourth  sacral  nerves,  and 
thence    passing    by    white    rami    communicantes    to    sympathetic 
ganglia ;  these  fibres  supply  the  descending  colon,  rectum,  anus,  and 
urino-genital  organs  in  the  pelvis,  and   they   constitute   the  nervi 
erigentes. 

It  will  be  noticed  that  in  the  spinal  district  white  rami  com- 
municantes only  occur  in  certain  regions :  but  all  the  spinal  nerves 
have  grey  rami  which  consist  of  post-ganglionic  fibres  returning  to 
the  spinal  nerves  for  distribution  to  the  blood-vessels  of  the  body 
wall,  to  the  muscles  which  erect  the  hairs  (pilo-motor  nerves),  and  to 
the  sweat  glands  of  the  skin. 

The  general  arrangement  of  such  nerves  is  represented  in  fig.  188. 

The  cell-station  of  any  particular  pre-ganglionic  fibre  is  not 
necessarily  situated  in  the  first  ganglion  to  which  it  passes;  the 
fibres  of  the  white  ramus  communicantes  of  the  second  thoracic  nerve, 
for  instance,  do  not  all  have  their  cell-stations  in  the  second  thoracic 
ganglion,  but  may  pass  upwards  or  downwards  in  the  chain  to  a 
more  or  less  distant  ganglion  before  they  terminate  by  arborising 
around  its  cells.  It  therefore  follows  that  fibres  that  leave  any 
given  spinal  nerve  by  its  white  ramus,  do  not  necessarily  return  as 
post-ganglionic  fibres  by  the  grey  ramus  to  the  same  spinal  nerve, 
although,  for  the  sake  of  simplifying  the  diagram,  they  are  repre- 
sented as  doing  so  in  fig.  188. 


CH.  XVII. 


THE  AUTONOMIC  PATH 


199 


SPINAL 
GANGLION 


V.M. 


FIG.  188. — Diagram  of  the  autonomic  path  in  the  spinal  region.  A.C.C.  anterior  cornual  cell  giving 
rise  to  a  large  motor  nerve-fibre  which  is  distributed  to  voluntary  muscle  (V.M.).  I.L.T.  a 
small  cell  of  the  intermedio-lateral  tract  giving  rise  to  a  small  medullated  nerve-fibre  which 
leaves  the  cord  by  an  anterior  root,  and  leaves  the  anterior  root  by  the  white  ramus  (W.R.) ;  it 
terminates  by  arborising  around  cells  in  a  ganglion  of  the  sympathetic  chain.  From  these  cells 
fresh  non-medullated  axons  continue  the  impulse,  and  return  to  the  spinal  nerve  by  the  grey 
ramus  (G.R.)  being  finally  distributed  to  involuntary  muscular  fibres  (I.M.).  The  pre-ganglionic 
path  is  coloured  red,  the  post-ganglionic  blue.  To  complete  the  diagram,  a  posterior  root-fibre  is 
also  shown  with  its  parent  cell  in  a  spinal  ganglion. 


LATERAL 
SPINAL  GANGLION 

Pre'-gangljonic  fibre 


SOLAR 
GANGLION 


Post-ganglionic  fibres 


A. 


SPINAL 
CORD 

r-^ 

LATERAL 

GANGLlCN 

Pre{-gang\ionic  fibre 

SOLAR 
GANGLION 

_^^ 

lA>«V      '-  - 

Post-ganglionic  fibres 

_^— 

£e>~-  - 

\ 

—  KT  / 

B. 


-._--'  Pre-gang.  fibre  iVj      '/ 


LATERAL 
SPINAL  GANGLION 

Pre/'-'ganglionic  fibre 


PCS  t-go  ng /ionic  fibre  "  ~ 

Flo    189.— Arrangement  of   pre-  and    post-ganglionic  fibres   in   splanchnic  and  inferior  splanchnic 

nerves.    (After  Langley.) 


200  THE   AUTONOMIC    NERVOUS    SYSTEM  [CH.  XVII. 

Furthermore,  there  are  many  fibres  of  the  white  rami  which  enter 
the  lateral  chain  of  ganglia  and  pass  through  them  without  com- 
municating with  their  cells  at  all,  and  never  return  to  the  spinal 
nerves  by  grey  rami.  They  pass  out  of  the  lateral  chain  either  to 
collateral  or  even  terminal  ganglia  before  reaching  their  cell-stations, 
whence  they  emerge  as  post-ganglionic  fibres.  This  is  the  case  for 
the  sympathetic  supply  of  the  blood-vessels  of  and  involuntary 
muscular  fibres  of  the  thoracic,  abdominal,  and  pelvic  viscera,  and  is 
therefore  true  for  such  important  nerves  as  the  cardiac  accelerators, 
the  splanchnics,  and  the  nervi  erigentes. 

Fig.  189  shows  the  course  of  the  splanchnic  fibres,  and  will 
assist  the  student  in  grasping  this  method  of  distribution. 

The  great  majority  are  arranged  as  in  A,  that  is  to  say  they  have 
their  cell-stations  in  the  solar  ganglion.  Comparatively  few  are 
arranged  as  in  B,  where  some  fibres  do  not  reach  their  cell-stations 
until  they  arrive  at  the  terminal  ganglion  situated  in  the  walls  of  the 
viscus  (for  instance,  the  pancreas)  to  which  they  are  distributed.  A 
few  possibly  and  occasionally  are  arranged  as  in  C,  with  a  cell -station 
for  some  of  their  branches  in  the  lateral  sympathetic  chain. 

It  will  be  noticed  that  if  any  post-ganglionic  fibre  is  traced  back- 
wards, there  is  one  and  only  one  cell-station  between  the  central 
nervous  system  and  the  ultimate  distribution  of  the  nerve  fibrils. 

The  next  question  that  arises  is,  how  have  all  these  facts  been 
ascertained ;  for  it  is  obviously  impossible  to  follow  the  individual 
fibres  with  the  microscope,  and  still  less  with  the  naked  eye.  The 
method  above  all  others  which  has  proved  successful  in  solving  the 
problem  is  the  nicotine  method,  originally  introduced  by  Langley 
and  Dickinson,  and  employed  since  by  Langley  mainly  in  conjunc- 
tion with  H.  K.  Anderson. 

The  Nicotine  Method. — Nicotine  in  small  doses  paralyses  nerve- 
cells,  but  not  nerve-fibres.  Before  the  paralytic  effect  of  nicotine 
comes  on,  it  excites  the  nerve-cells,  and  this  in  the  case  of  the  blood- 
vessels causes  a  general  constriction  of  the  arterioles,  and  a  con- 
sequent rise  of  arterial  pressure.  It  is  still  a  matter  of  uncertainty 
whether  the  drug  produces  these  effects  on  the  nerve-cells  themselves 
or  on  the  terminal  arborisations  (synapses)  of  the  fibres  that  sur- 
round them,  or  on  receptive  substances  (see  p.  164)  either  in  the 
cells  or  present  at  the  synaptic  junctions.  But  whichever  of  these 
modes  of  action  is  the  correct  one,  the  main  result  is  the  same;  a 
nervous  impulse  which  reaches  a  ganglion  by  a  pre-ganglionic  fibre 
cannot  get  across  to  the  corresponding  post-ganglionic  fibres  if  the 
animal  is  poisoned  with  nicotine.  Stimulation  of  the  anterior  nerve- 
roots,  or  of  the  white  rami  no  longer  produces  movements  of  the 
involuntary  muscular  tissues,  because  the  paralysed  cell-stations  act 
as  blocks  to  the  propagation  of  the  impulses.  If,  however,  post- 


CH.  XVII.]  AUTONOMIC   PATHS  201 

ganglionic  fibres  are  stimulated,  the  usual  effects  (for  instance, 
constriction  of  blood-vessels,  erection  of  the  hairs,  etc.)  take  place. 
If  instead  of  injecting  nicotine  into  the  circulation,  and  so  producing 
a  general  effect,  the  nicotine  is  painted  over  one  or  more  ganglia, 
there  will  be  a  block  in  those  fibres  only  which  have  their  cell- 
stations  in  those  particular  ganglia.  By  patiently  examining  all  the 
ganglia  in  this  way  in  turn,  stimulating  the  fibres  that  enter  it  and 
those  that  leave  it,  Langley  and  his  colleagues,  after  years  of  work, 
have  been  successful  in  localising  the  cell-stations  on  most  of  the 
autonomic  paths  in  the  body. 

We  shall  in  later  chapters  be  considering  the  autonomic  nerve 
supply  of  the  individual  organs,  but  it  will  be  convenient  here  to 
state  in  a  general  way  the  main  course  of  the  distribution  of  these 
nerves;  we  have  seen  that  the  outflow  from  the  central  nervous 
system  occurs  in  four  regions,  and  therefore  we  may  take  these 
seriatim. 

1.  The  autonomic  nerve-fibres  which  arise  from  the  mid-brain. — 
These  emerge  by  the  third  nerve ;  the  pre-ganglionic  fibres  pass  to 
the  ciliary  ganglion;   the  post-ganglionic  arising  from  the  cells  of 
this  ganglion  run  in  the  short  ciliary  nerves  to  supply  the  intrinsic 
muscles  of  the  eyeball  (sphincter  iridis  and  ciliary  muscle). 

2.  The   autonomic    nerve-fibres    which    arise  from    the    medulla 
dblongata. — These  emerge  by  the  following  nerves : — 

(a)  Seventh  and  ninth  nerves.     These  supply  the  blood-vessels 
with  vaso-dilator  fibres  and  also  the  secreting  glands  in  the  nose  and 
mouth   region.     Many   of   these   fibres   (for  instance,   those  in  the 
chorda  tympani)  get  bound  up  with  branches  of  the  fifth  nerve,  and 
are   distributed   with   them.     The  ganglia   on   the   course  of  these 
fibres  are  the   spheno-palatine,   otic,  submaxillary,   and   sublingual 
ganglia. 

(b)  Tenth  and   eleventh   nerves.     These  are  distributed  by  the 
branches  of  the  tenth  or  vagus  nerve  to  the  oesophagus,  stomach,  and 
part  of  the  intestine,  to  the  bronchial  muscles,  to  the  heart,  and  to 
the  gastric  and  pancreatic  secretory  mechanism.     Here  our  know- 
ledge of  the  localisation  of  the  cell-stations  is  not  so  exact  as  it  is  in 
other  parts ;  some  of  the  fibres  appear  to  have  their  cell-stations  in 
the  ganglion  on  the  trunk  of  the  vagus,  but  in  most  cases  they  do  not 
become  post-ganglionic  until  the  terminal  ganglia  in  the  walls  of  the 
various  organs  mentioned  are  reached. 

3.  The  autonomic  fibres  which  arise  from  the  thoracic  region  of  the 
spinal  cord. — These  constitute  the   best  known  of   the  autonomic 
fibres,  and  we  may  describe   them  according  to  their  distribution 
under  the  following  two  headings : — 

(a)  The  white  rami  leave  the  spinal  nerves  and  find  their  cell- 
stations  in  lateral  ganglia,  returning  by  the  grey  rami  for  distribution 


202  THE   AUTONOMIC   NERVOUS   SYSTEM  [CH.  XVII. 

to  the  involuntary  muscular  tissue  and  glands  in  the  body  walls  and 
skin. 

Thus  in  the  lateral  chain  of  ganglia  we  find  the  cells  on  the 
course  of  the  pilo-motor  nerves,  of  the  nerves  to  the  sweat  glands, 
possibly  of  the  splenic  nerves,  and  last  but  not  least,  of  the  vaso- 
constrictors of  the  head,  limbs,  and  body  wall.  Indeed,  at  one  time, 
Gaskell  suggested  that  the  lateral  chain  should  be  called  the  chain  of 
vaso-motor  ganglia.  In  general  terms  the  cell-stations  are  situated 
in  ganglia  that  correspond  with  the  various  spinal  segments ;  those 
for  the  lower  limbs,  for  instance,  being  further  down  the  chain  than 
those  for  the  trunk  and  upper  limb.  The  vaso -constrictor  fibres 
destined  for  the  head,  ascend  the  cervical  sympathetic  and  do  not 
reach  their  cell-station  until  they  arrive  at  the  superior  cervical 
ganglion. 

(b)  The  pre-ganglionic  fibres  traverse  the  lateral  ganglia,  and 
emerge  still  as  pre-ganglionic  fibres,  which  find  their  cell-stations  in 
more  or  less  outlying  ganglia  (collateral  or  terminal).  We  have 
already  taken  the  splanchnic  nerve  as  one  example  of  this  mode  of 
distribution ;  the  nerve  contains  inter  alia  the  vaso-constrictor  fibres, 
and  viscero-inhibitory  fibres  of  the  abdominal  organs.  The  hypo- 
gastric  nerve  arises  in  a  similar  way  from  the  inferior  mesenteric 
ganglion  and  joins  the  pelvic  plexus.  The  medullated  pre- 
ganglionic  fibres  of  this  nerve  arise  from  the  upper  lumbar  nerve- 
roots. 

4.  The  autonomic  nerve-fibres  which  arise  from  the  sacral  region  of 
the  spinal  cord. — The  pre-ganglionic  fibres  emerge  in  the  white  rami 
of  the  second,  third,  and  fourth  sacral  nerves.  They  pass  through 
the  sacral  ganglia  of  the  lateral  chain  without  forming  connections 
with  any  cells  there,  and  they  pass  on  as  the  nervus  erigens,  or  pelvic 
nerve,  to  join  the  pelvic  plexus.  The  fibres  of  this  nerve  supply  vaso- 
dilator fibres  to  the  external  generative  organs  (whence  its  name),  to 
the  rectum  and  anus,  and  motor  fibres  to  the  musculature  of  the 
descending  colon  and  rectum,  and  have  their  cell-stations  in  the  small 
scattered  ganglia  of  the  pelvic  plexus,  or  in  terminal  ganglia  in  the 
walls  of  the  viscera  they  supply. 

Looking  at  the  involuntary  muscles  for  a  moment  from  a 
rather  different  point  of  view,  we  see  that  they  (or  most  of  them) 
differ  from  the  voluntary  muscles  in  being  supplied  by  two  sets  of 
nerve-fibres  with  opposite  functions.  In  the  case  of  the  heart,  we 
have  an  accelerator  set  which  course  through  the  sympathetic,  and 
an  inhibitory  set  which  course  through  the  vagus.  In  the  case  of 
the  blood-vessels,  we  have  an  accelerator  set  called  vaso-constrictors, 
and  an  inhibitory  set  called  vaso -dilators.  In  the  case  of  the  con- 
tractile viscera  we  have  also  viscero-accelerator  and  viscero-inhibitory, 
which  respectively  hasten  and  lessen  their  peristaltic  movements. 


CH.  XVII.]  OBJECT   OF  AUTONOMIC   GANGLIA  203 

Adopting  Gaskell's  nomenclature,  we  may  term  the  accelerator 
groups  of  nerves  katabolic,  because  they  increase  the  activity  of  the 
muscles  they  supply,  bringing  about  an  increase  of  wear  and  tear 
and  an  increase  in  the  discharge  of  waste  materials,  the  products  of 
their  activity.  The  inhibitory  nerves,  on  the  other  hand,  are  ana- 
bolic, as  they  produce  a  condition  of  rest  in  the  tissues  they  supply, 
and  so  give  an  opportunity  for  repair,  or  constructive  metabolism. 

As  a  general  rule,  though  there  are  exceptions  to  it,  the  cell- 
stations  of  the  anabolic  nerves  are  in  collateral  or  terminal  ganglia, 
whereas  the  cell-stations  for  katabolic  nerves  are  in  the  lateral  chain, 
or  in  some  cases  in  collateral  ganglia. 

Our  descriptions  and  diagrams  have  further  shown  us  that  post- 
ganglionic  fibres  are  more  numerous  than  pre-ganglionic  fibres,  and 
this  brings  us  to  the  main  object  served  by  the  ganglia  on  the 
autonomic  nerves.  Nature  has,  as  it  were,  before  her  the  problem 
of  supplying  with  nerves  the  vast  mass  of  muscles  in  the  body,  and 
the  space  at  her  command  in  the  various  exits  from  the  cranium 
and  spinal  canal  does  not  allow  of  more  than  a  comparatively  small 
outflow  from  the  central  nervous  system. 

The  difficulty  is  met  to  some  extent  by  the  branching  of  the  out- 
flowing nerve-fibres,  and  in  the  case  of  the  voluntary  muscles  this 
appears  to  be  sufficient.  The  most  striking  example  of  this  can  be 
seen  in  the  electrical  organ  of  the  Malapterurus,  where  the  millions 
of  its  subdivisions  on  each  side  of  the  body  are  all  supplied  by  the 
branches  of  a  single  axis  cylinder  process  originating  from  a  single 
giant  nerve-cell  in  the  brain. 

But  in  the  case  of  the  involuntary  muscular  tissue  there  is  an 
additional  means  of  distribution,  for  each  fibre  that  leaves  the 
central  nervous  system  arborises  around  a  number  of  cells  in  the 
autonomic  ganglia,  and  thus  the  impulse  is  transferred  to  a  large 
number  of  new  axis  cylinder  processes. 

The  name  sympathetic  was  originally  bestowed  on  the  system  of 
nerves  we  are  considering,  because  the  ganglia  were  believed  to  be 
the  centres  for  reflex  actions,  or  sympathetic  actions  as  they  were 
formerly  designated. 

During  their  work  on  autonomic  nerves  Langley  and  Anderson 
have  once  more  investigated  this  ancient  question,  but  the  only 
instances  where  such  a  thing  seemed  possible  were  the  following : — 
When  all  the  nervous  connections  of  the  inferior  mesenteric  ganglion 
are  divided  except  the  hypogastric  nerves,  stimulation  of  the  central 
end  of  one  hypogastric  causes  contraction  of  the  bladder,  the  efferent 
path  to  which  is  the  other  hypogastric  nerve.  But  the  action  is 
not  truly  reflex;  it  is  caused  by  the  stimulation  of  the  central 
ends  of  motor-fibres  which  issue  from  the  spinal  cord,  and  which 
after  passing  through  the  ganglion  send  branches  down  each 


204  THE   AUTONOMIC   NERVOUS   SYSTEM  [CH.  XVII. 

hypogastric  nerve.  The  experiment  is  in  fact  similar  to  Kiihne's 
gracilis  experiment  (p.  160).  They  also  observed  an  apparent  reflex 
excitation  of  certain  nerves  supplying  the  erector  muscles  of  the 
hairs  (pilo-motor  nerves)  through  other  sympathetic  ganglia;  but 
this  is  explicable  in  the  same  way. 

It  certainly  is  the  case  that  under  normal  circumstances  the 
centres  for  reflex  action  are  in  the  central  nervous  system.  But 
there  do  appear  to  be  some  conditions  in  which  it  is  possible  for 
ganglia  to  assume  this  function.  The  recovery  of  vaso-motor  tone, 
and  of  tone  in  certain  viscera  after  destruction  of  extensive  tracts  of 
the  spinal  cord,  or  the  persistence  of  peristaltic  action  in  the  intes- 
tine after  cutting  through  all  its  nerves,  are  cases  in  point.  (See 
further,  under  Intestinal  Movements,  and  Spinal  Visceral  Eeflexes.) 
Such  action  forms,  in  fact,  the  chief  justification  for  the  adoption  of 
the  new  term,  autonomic. 

Afferent  Nerves  of  the  Autonomic  System. 

Up  to  the  present  point,  we  have  only  considered  the  efferent 
fibres  of  the  autonomic  nerves.  No  survey  of  the  autonomic  system 
will,  however,  be  complete  which  does  not  include  an  account  of  the 
afferent  fibres.  This  will  not  occupy  much  space,  because  our  infor- 
mation on  this  side  of  the  subject  is  so  scanty. 

The  " vegetative"  functions  of  the  body  are  carried  out  inde- 
pendently of  volition,  and  under  normal  circumstances  they  also 
cause  no  sensations.  In  pre-ansesthetic  days,  surgeons  discovered 
that  the  viscera  possess  no  sensibility  in  the  ordinary  sense ;  they 
may  be  handled  and  cut  without  producing  pain ;  and,  with  the 
exception  of  the  oesophagus,  they  are  insensitive  also  to  heat  and 
cold. 

Still,  under  abnormal  conditions  we  become  conscious  of  their 
activity,  especially  if  it  is  excessive,  as  for  instance  in  the  very  severe 
pain  which  the  various  forms  of  colic  give  rise  to.  But  even  under 
these  circumstances  there  is  great  difficulty  in  accurately  localising 
the  pain. 

The  afferent  or  sensory  fibres  are  much  less  numerous  than  those 
which  are  efferent.  This  has  been  ascertained  by  cutting  the 
anterior  nerve  roots  which  communicate  with  an  autonomic  nerve ; 
the  efferent  fibres  will  degenerate  peripherally,  but  the  sensory  fibres 
will  remain  intact,  and  the  relative  number  of  healthy  and  degene- 
rated fibres  can  then  be  counted.  Thus  in  the  splanchnic  and 
hypogastric  nerves  about  one-tenth  of  the  fibres  are  found  to  be 
sensory;  and  in  the  pelvic  nerve  about  one-third  of  the  total  fibres 
are  sensory. 

The  grey  rami  contain  few  if  any  sensory  fibres;  excitation  of 


OH.  XVII.]  REFERRED   PAIN  205 

their  central  ends  produces  neither  pain  nor  reflex  action ;  and  the 
same  is  true  for  the  cervical  sympathetic. 

On  the  other  hand,  excitation  of  the  central  ends  of  the  white 
rami  produces  reflex  movements,  especially  in  involuntary  muscles, 
as  is  evidenced  by  a  rise  of  blood-pressure  due  to  constriction  of 
peripheral  arteries;  this  is  especially  the  case  with  white  rami 
connected  with  thoracic  and  abdominal  viscera. 

It  is  therefore  deduced  from  this  that  the  sensory  autonomic 
fibres  enter  the  central  nervous  system  by  the  white  rami,  but 
whether  they  come  into  relationship  with  the  cells  of  either  sympa- 
thetic or  spinal  ganglia  is  very  uncertain.  Possibly  the  cells  of 
origin  are  within  the  spinal  cord  itself.  In  the  cranial  region  we 
have  some  information  especially  in  connection  with  the  vagus 
nerves  of  the  existence  of  afferent  fibres,  which  we  shall  be  studying 
in  detail  in  connection  with  the  heart  and  the  lungs. 

Referred  Pain. — Localisation  of  painful  or  uncomfortable  feelings 
arising  from  disorders  of  internal  organs  is  always  very  difficult. 
But  they  are  associated  with  pains  in  the  skin,  and  this  referred  pain, 
as  it  is  called,  often  plays  an  important  part  in  ascertaining  the 
position  of  internal  maladies.  Pains  arising  from  intestinal  irritation 
are  referred  to  the  skin  of  the  lumbar  region  in  the  area  supplied  by 
the  lower  thoracic  nerves;  pains  originating  in  the  stomach  are 
referred  to  an  area  of  skin  above  this  at  the  lower  margin  of  the 
ribs,  those  from  the  heart  to  the  shoulder  region,  and  so  forth. 

Each  viscus  appears  to  be  correlated  with  a  definite  patch  or 
band  of  skin ;  this  may  even  be  tender  on  pressure.  Eoss's  sugges- 
tion that  the  pain  in  such  case  is  referred  by  sensory  cutaneous  fibres 
ending  in  the  same  segments  of  the  cord  as  do  the  afferent  fibres 
from  the  viscera  in  question,  has  been  placed  beyond  doubt  by  the 
subsequent  work  of  Mackenzie  and  of  Head. 


CHAPTEK  XVIII 

TKOPHIC   NERVES 

NERVES  exercise  a  trophic  or  nutritive  influence  over  the  tissues  and 
organs  they  supply ;  for  when  a  nerve  going  to  an  organ  is  cut,  the 
wasting  or  degenerative  process  continues  beyond  the  nerve;  the 
muscles  it  supplies  waste  also,  and  waste  much  more  rapidly  than 
can  be  explained  by  simple  disuse.  The  same  is  seen  in  the  testicle 
after  section  of  the  spermatic  cord ;  and  in  the  disease  of  joints  called 
Charcot's  disease,  the  trophic  changes  are  to  be  explained  by  disease 
of  the  nerves  supplying  them.  After  the  division  of  the  fifth  cranial 
nerve  there  is  loss  of  sensation  in  the  corresponding  side  of  the 
face:  the  cornea  in  two  or  three  days  begins  to  get  opaque,  and 
this  is  followed  by  a  slow  inflammatory  process  which  may  lead  to  a 
destruction  not  only  of  the  cornea,  but  of  the  whole  eyeball.  The 
same  is  seen  in  man ;  when  the  fifth  nerve  is  diseased  or  pressed 
upon  by  a  tumour  beyond  the  Gasserian  ganglion,  the  result  is  loss 
of  sensation  in  the  face  and  conjunctiva,  an  eruption  (herpes)  appears 
on  the  face,  and  ulceration  of  the  cornea  leading  in  time  to  disinteg- 
ration of  the  eyeball  may  occur  too.  In  disease  such  as  haemorrhage 
in  the  spinal  ganglia  there  is  a  similar  herpetic  eruption  on  the  skin 
(shingles). 

In  the  case  of  the  fifth  nerve  the  evidence  that  there  are  special 
nerve-fibres  to  which  these  trophic  changes  are  due,  is  an  experiment 
by  Meissner  and  Buttner,  who  found  that  division  of  the  most 
internal  fibres  is  most  potent  in  producing  them. 

Those,  however,  who  do  not  believe  in  special  trophic  nerves, 
attribute  the  changes  in  the  eyeball  to  its  loss  of  sensation.  Dust, 
etc.,  is  not  felt  by  the  cornea,  and  is  therefore  allowed  to  accumulate 
and  set  up  inflammation.  This  is  supported  by  the  fact  that  if  the 
eyeball  is  protected  by  sewing  the  eyelids  together  the  trophic  results 
do  not  ensue.  On  the  other  hand,  in  paralysis  of  the  seventh  nerve, 
the  eyeball  is  much  more  exposed,  and  yet  no  trophic  disorders 
follow. 

Others  have  attributed  the  change  to  increased  vascularity  due 
to  disordered  vaso-motor  changes;  against  this  is  the  fact  that  in 

206 


CH.  XVIII.]  TROPHIC   NERVES  207 

disease  of  the  cervical  sympathetic,  the  disordered  vaso-motor 
phenomena  which  ensue  do  not  lead  to  the  disorders  of  nutrition  we 
have  described.  Nevertheless  in  trophic  disorders,  it  is  very  difficult 
to  be  sure  that  the  disordered  metabolism  is  not  in  part  due  to 
vascular  disturbances. 

There  can,  therefore,  be  but  little  doubt  that  we  have  to  deal 
with  the  trophic  influence  of  nerves ;  *  but  the  dust,  etc.,  which  falls 
on  the  cornea  must  be  regarded  as  the  exciting  cause  of  the  ulceration. 
The  division  or  disease  of  the  nerve  acts  as  the  predisposing  cause. 
The  eyeball  is  more  than  usually  prone  to  undergo  inflammatory 
changes,  with  very  small  provocation. 

The  same  explanation  holds  in  the  case  of  the  influence  of  the 
vagi  on  the  lungs.  If  both  these  nerves  are  divided,  the  animal 
usually  dies  within  a  week  or  a  fortnight  from  a  form  of  pneumonia 
called  vagus  pneumonia,  in  which  gangrene  of  the  lung  substance  is 
a  marked  characteristic.  Here  the  predisposing  cause  is  the  division 
of  the  pneumogastric  nerves ;  the  exciting  cause  is  the  entrance  of 
particles  of  food  into  the  air  passages,  which  on  account  of  the  loss 
of  sensation  in  the  larynx  and  neighbouring  parts  are  not  coughed 
up.  Another  trophic  disturbance  that  follows  division  of  the  vagi  is 
fatty  degeneration  of  the  heart. 

Many  bedsores  are  due  to  prolonged  confinement  in  bed  with 
bad  nursing ;  these  are  of  slow  onset.  But  there  is  one  class  of  bed- 
sores which  are  acute;  these  are  especially  met  with  in  cases  of 
paralysis,  due  to  disease  of  the  spinal  cord ;  they  come  on  in  three  or 
four  days  after  the  onset  of  the  paralysis  in  spite  of  the  most  careful 
attention ;  they  cannot  be  explained  by  vaso-motor  disturbance,  nor 
by  loss  of  sensation ;  the  nutrition  of  the  skin  is  so  greatly  impaired 
that  the  mere  contact  of  it  with  the  bed  for  a  few  days  is  sufficient 
to  act  as  the  exciting  cause  of  the  sore. 

It  will  be  noticed  that  in  some  instances  of  trophic  disorder  the  nerves  which  are 
injured  are  efferent ;  the  muscular  wasting  that  occurs  when  a  muscular  nerve  is  cut 
is  the  best  marked  example  of  this.  In  nerve  itself  Wallerian  degeneration  follows 
the  direction  of  growth,  which,  as  a  rule,  is  the  direction  in  which  the  nerve  transmits 
impulses.  The  acute  Wallerian  change  does  not  actually  leap  synapses,  still  the 
trophic  influence  of  one  set  of  neurons  upon  a  second  set  among  which  the  axons  of 
the  first  set  terminate  is  shown  by  a  slow  wasting  process,  of  which  chromatolysis 
is  an  early  visible  sign.  In  the  peripheral  axons  of  the  cells  of  the  spinal  and 
corresponding  cranial  ganglia,  the  trophic  disorder  follows  a  peripheral  direction, 
while  impulses  are  carried  in  the  opposite  or  afferent  direction.  The  trophic  influence 
here  travels  against  the  stream  of  impulse.  It  cannot  fail  to  be  a  striking  fact  that 
the  most  marked  trophic  disorders  with  which  we  are  acquainted,  herpes,  acute 
bedsores,  Charcot's  disease,  eye  changes  after  division  or  injury  to  the  fifth  nerve, 
vagus  pneumonia,  etc.,  are  due  to  interference  with  sensory  channels.  Loss  of 
sensation  is  the  great  predisposing  cause  of  nutritive  mischief. 

*  The  proof,  however,  that  there  are  distinct  nerve-fibres  anatomically  is  not 
very  conclusive. 


CHAPTER  XIX 

THE   CIRCULATORY   SYSTEM 

THE  circulatory  system  consists  of  the  heart,  the  arteries,  or  vessels 
that  carry  the  blood  from  the  heart  to  other  parts  of  the  body,  the 
veins,  or  vessels  that  carry  the  blood  back  to  the  heart  again,  and  the 
capillaries,  a  network  of  minute  tubes  which  connect  the  terminations 
of  the  smallest  arteries  to  the  commencements  of  the  smallest  veins. 
We  shall  also  have  to  consider  in  connection  with  the  circulatory 
system,  the  lymphatics,  which  are  vessels  that  convey  back  the 
lymph  (the  fluid  which  exudes  through  the  thin  walls  of  the  blood- 
capillaries)  to  the  large  veins  near  to  their  entrance  into  the  heart, 
and  the  large  lymph  spaces  contained  in  the  serous  membranes. 

The  Heart. 

This  is  the  great  central  pump  of  the  circulatory  system.  It  lies 
in  the  chest  between  the  right  and  left  lungs  (fig.  190),  and  is 
enclosed  in  a  covering  called  the  pericardium.  The  pericardium  is 
an  instance  of  a  serous  membrane.  Like  all  serous  membranes  it 
consists  of  two  layers;  each  consists  of  fibrous  tissue;  one  layer 
envelops  the  heart  and  forms  its  outer  covering  or  epicardium; 
this  is  the  visceral  layer  of  the  pericardium ;  the  other  layer  of  the 
pericardium,  called  its  parietal  layer,  is  situated  at  some  little  distance 
from  the  heart,  being  attached  below  to  the  diaphragm,  the  partition 
between  the  thorax  and  the  abdomen.  The  visceral  and  parietal 
layers  are  continuous  for  a  short  distance  along  the  great  vessels  at 
the  base  of  the  heart,  and  so  form  a  closed  sac.  This  sac  is  lined  by 
endothelium;  in  health  it  contains  just  enough  lymph  (pericardial 
fluid)  to  lubricate  the  two  surfaces  and  enable  them  to  glide  over 
each  other  smoothly  during  the  movements  of  the  heart.  The 
presence  of  numerous  elastic  fibres  in  the  epicardium  enables  it  to 
follow  without  hindrance  the  changing  shape  of  the  heart  itself ;  but 
the  parietal  layer  of  the  pericardium  appears  to  be  inextensible,  and 
so  it  limits  the  dilatation  of  the  heart. 


CH.  XIX.] 


THE    HEART 


209 


The  pericardium  is  a  comparatively  simple  serous  membrane,  because  the 
organ  it  encloses  is  a  single  one  of  simple  external  form.  All  serous  membranes 
are  of  similar  structure  ;  thus  the  pleura  which  encloses  the  lung,  and  the  peritoneum 
which  encloses  the  abdominal  viscera  differ  from  it  only  in  anatomical  arrangement. 
The  great  complexity  of  the  peritoneum  is  due  to  its  enclosing  so  many  organs. 
Every  serous  membrane  consists  of  a  visceral  layer  applied  to  the  organ  or  organs 
it  encloses ;  and  a  parietal  layer  continuous  with  this  in  contiguity  with  the  parietes 
or  body-walls. 


Bight 

Lung 


Pulmonary 
Artery. 


Left  Lung. 


The  Chambers  of  the  Heart. — The  interior  of  the  heart  is 
divided  by  a  longitudinal  partition  into  two  chief  cavities — right  and 
left.  Each  of  these  chambers  is  again  subdivided  transversely  into 
an  upper  and  a  lower  portion,  called  respectively,  auricle  and  ventricle, 
which  freely  communicate  one  with  the  other ;  the  aperture  of  com- 
munication, however,  is  guarded  by  valves,  so  disposed  as  to  allow 
blood  to  pass  freely  from 
the  auricle  into  the  ven- 
tricle, but  not  in  the  oppo- 
site direction.  There  are 
thus  four  cavities  in  the 
heart — the  auricle  and  ven- 
tricle of  one  side  being 
quite  separate  from  those 
of  the  other  (figs.  191, 192). 

The  right  auricle  is  a 
thin -walled  cavity  of  quad- 
rilateral shape,  prolonged 
at  one  corner  into  a  tongue- 
shaped  portion,  the  right 
auricular  appendix,  which 
slightly  overlaps  the  exit  of 
the  aorta,  from  the  heart. 

The  interior  is  smooth, 
being  lined  with  the  general 
lining  of  the  heart,  the 
endocardium,  and  into  it 
open  the  superior  and  inferior  venae  cavae,  or  great  veins,  which 
convey  the  blood  from  all  parts  of  the  body  to  the  heart.  The 
opening  of  the  inferior  vena  cava  is  protected  and  partly  covered  by 
a  membrane  called  the  Eustachian  valve.  In  the  posterior  wall  of  the 
auricle  is  a  slight  depression  called  the/ossa  ovalis,  which  corresponds 
to  an  opening  between  the  right  and  left  auricles  which  exists  in 
foetal  life.  The  coronary  sinus,  or  the  dilated  portion  of  the  coronary 
vein,  also  opens  into  this  chamber. 

The  right  ventricle  occupies  the  chief  part  of  the  anterior  surface 
of  the  heart,  as  well  as  a  small  part  of  the  posterior  surface.  It 
takes  no  part  in  the  formation  of  the  apex.  On  section  after  death 

O 


Diaphragm. 

FIG.  190.— View  of  heart  and  lungs  in  situ.  The  front 
portion  of  the  chest-wall  and  the  outer  or  parietal 
layers  of  the  pleurne  and  pericardium  have  been  re- 
moved. The  lungs  are  partly  collapsed. 


210 


THE   CIRCULATORY   SYSTEM 


[CH.  XIX. 


its  cavity,  in  consequence  of  the  encroachment  upon  it  of  the  septum 
ventriculorum,  is  crescentic  (fig.  193);  it  has  two  openings,  one 
communicating  with  the  right  auricle,  and  the  other  with  the 
pulmonary  artery ;  both  orifices  are  guarded  by  valves,  the  former 
called  tricuspid  and  the  latter  semilunar. 


FIG.  191. — The  right  auricle  and  ventricle  opened,  and  a  part  of  their  right  and  anterior  walls  removed, 
so  as  to  show  their  interior.  £.— 1,  superior  vena  cava ;  2,  inferior  vena  cava ;  2',  hepatic  veins  cut 
short ;  3,  right  auricle  ;  3',  placed  in  the  fossa  ovalis,  below  which  is  the  Eustachian  valve ;  3",  is 
placed  close  to  the  aperture  of  the  coronary  vein  ;  +  +,  placed  in  the  auriculo-ventricular  groove, 
where  a  narrow  portion  of  the  adjacent  walls  of  the  auricle  and  ventricle  has  been  preserved  ;  4,  4, 
cavity  of  the  right  ventricle,  the  upper  figure  is  immediately  below  the  semilunar  valves ;  4',  large 
columna  carnea  or  musculus  papillaris ;  5,  5',  5",  tricuspid  valve  ;  6,  placed  in  the  interior  of  the 
pulmonary  artery,  a  part  of  the  anterior  wall  of  that  vessel  having  been  removed,  and  a  narrow 
portion  of  it  preserved  at  its  commencement,  where  the  semilunar  valves  are  attached  ;  7,  concavity 
of  the  aortic  arch  close  to  the  cord  of  the  ductus  arteriosus  ;  8,  ascending  part  or  sinus  of  the  arch 
covered  at  its  commencement  by  the  auricular  appendix  and  pulmonary  artery  ;  9,  placed  between 
the  innominate  and  left  carotid  arteries ;  10,  appendix  of  the  left  auricle ;  11,  11,  the  outside  of  the 
left  ventricle,  the  lower  figure  near  the  apex.  (Allen  Thomson.) 

The  left  auricle  is  best  seen  from  behind.  It  receives  on  either 
side  two  pulmonary  veins.  The  left  auricle  is  somewhat  thicker  than 
the  right.  The  left  auriculo-ventricular  orifice  is  oval,  and  a  little 
smaller  than  that  on  the  right  side. 


CH.  XIX.] 


THE   HEART 


211 


The  left  ventricle  occupies  the  chief  part  of  the  posterior  surface. 
In  it  are  two  openings  very  close  together,  viz.,  the  auriculo-ventri- 


Fic.  192. — The  left  auricle  and  ventricle  opened  and  a  part  of  their  anterior  and  left  walls  removed.  £. 
— The  pulmonary  artery  has  been  divided  at  its  commencement;  the  opening  into  the  left  ventricle 
is  carried  a  short  distance  into  the  aorta  between  two  of  the  segments  of  the  semilunar  valves  ;  and 
the  left  part  of  the  auricle  with  its  appendix  has  been  removed.  The  right  auricle  is  out  of  view. 
1,  the  two  right  pulmonary  veins  cut  short ;  their  openings  are  seen  within  the  auricle  ;  1',  placed 
within  the  cavity  of  the  auricle  on  the  left  side  of  the  septum  and  on  the  part  which  forms  the 
remains  of  the  valve  of  the  foramen  ovale,  of  which  the  crescentic  fold  is  seen  towards  the  left  hand 
of  1' ;  2,  a  narrow  portion  of  the  wall  of  the  auricle  and  ventricle  preserved  round  the  auriculo- 
ventricular  orifice ;  3,  3',  the  cut  surface  of  the  walls  of  the  ventricle,  seen  to  become  very  much 
thinner  towards  3",  at  the  apex  ;  4,  a  small  part  of  the  anterior  wall  of  the  left  ventricle  which  has 
been  preserved  with  the  principal  anterior  columna  carnea  or  musculus  papillaris  attached  to  it ; 
5,  5,  musculi  papillares ;  5',  the  left  side  of  the  septum,  between  the  two  ventricles,  within  the 
cavity  of  the  left  ventricle ;  6,  6',  the  mitral  valve  ;  7,  placed  in  the  interior  of  the  aorta,  near  its 
commencement  and  above  the  three  segments  of  its  semilunar  valve  which  are  hanging  loosely 
together ;  7',  the  exterior  of  the  great  aortic  sinus ;  8,  the  root  of  the  pulmonary  artery  and  its 
semilunar  valves;  8',  the  separated  portion  of  the  pulmonary  artery  remaining  attached  to  the 
aorta  by  9,  the  cord  of  the  ductus  arteriosus  ;  10,  the  arteries  rising  from  the  summit  of  the  aortic 
arch.  (Allen  Thomson.) 

cular  and  the  aortic,  guarded  by  the  valves  corresponding  to  those  of 
the  right  side  of  the  heart,  viz.,  the  bicuspid  or  mitral  and  the  semi- 


212  THE  CIRCULATORY   SYSTEM  [CH.  XIX. 

lunar.  The  walls  of  the  left  ventricle,  which  in  man  are  nearly 
half  an  inch  in  thickness,  are  about  three  times  as  thick  as  those 
of  the  right. 


Cavity  of  right  ventricle.  -L^ 

^M»<V:-  ^ssas.  ^^^^.  Cavity  of  left  ventricle. 


FIG.  193.— Transverse  section  of  bullock's  heart  in  a  state  of  cadaveric  rigidity.    (Dalton.) 

Capacity  of  the  Chambers. — During  life  each  ventricle  is 
capable  of  containing  about  three  ounces  of  blood.  '  The  capacity  of 
the  auricles  is  rather  less  than  that  of  the  ventricles :  the  thick- 
ness of  their  walls  is  considerably  less.  The  latter  condition  is 
adapted  to  the  small  amount  of  force  which  the  auricles  require  in 
order  to  empty  themselves  into  their  adjoining  ventricles ;  the  former, 
to  the  circumstance  that  the  ventricles  are  partly  filled  with  blood 
before  the  auricles  contract. 

Size  and  Weight  of  the  Heart. — The  heart  is  about  5  inches 
long  (about  12'6  cm.),  3J  inches  (8  cm.)  greatest  width,  and  2£ 
inches  (6*3  cm.)  in  its  extreme  thickness.  The  average  weight  of 
the  heart  in  the  adult  is  from  9  to  10  ounces  (about  300  grms.) ; 
its  weight  gradually  increases  throughout  life  till  middle  age;  it 
diminishes  in  old  age. 

Structure. — The  main  thickness  of  the  heart-wall  is  composed 
of  muscular  tissue;  but  a  ring  of  connective  tissue,  to  which  many 
of  the  muscular  fibres  are  attached,  lies  between  each  auricle  and 
ventricle  at  the  auriculo-ventricular  orifice.  The  embryonic  origin 
of  the  heart  from  a  single  tube  is  indicated  by  the  fact  that  the 
superficial  layers  of  muscle  of  the  auricles  and  also  of  the  ventricles 
encircle  the  chambers  of  the  two  sides;  this  ensures  their  simul- 
taneous contraction.  Very  varying  accounts  are  given  of  the  arrange- 
ment of  the  layers  of  fibres  especially  in  the  ventricles,  but  the  best 
appears  to  be  the  following :  in  the  interior  we  have  muscular  fibres 
which  are  thrown  into  the  columnse  carnese,  and  papillary  muscles ; 
it  may  be  called  the  papillary  layer.  Next  come  fibres  arranged 
circularly,  some  round  the  left,  and  others  round  the  right  ventricle ; 
this  layer  called  the  circular  layer  comprises  the  main  thickness  of 
the  ventricular  wall,  and  the  act  of  propelling  the  blood  into  the 
arteries  is  chiefly  performed  by  it.  External  to  this,  arranged  in  three 
principal  bands,  are  fibres  which  spirally  encircle  one  ventricle,  and 


CH.  XIX.] 


VALVES    OF   THE   HEART 


213 


then  pass  by  the  septum  around  the  other  ventricle,    and  finally 
terminate  at  the  base  of  the  heart :  this  is  called  the  spiral  layer. 

In  the  amphibian  heart  there  is  an  obvious  muscular  con- 
nection between  the  auricle  and  ventricle.  A  similar  muscular 
link  mingled  with  non-medullated  nerve -fibres  also  occurs  in  the 
mammal.  This  bundle  passes  down  from  the  interauriciilar 
septum  to  the  interventricular  septum,  where  it  divides  into  two 
bundles,  one  for  each  ventricle :  its  fibres  are  peculiar  in  structure 
and  are  known  as  Purkinje's  fibres  (p.  71).  It  is  called  the  auriculo- 
ventricular  bundle.  At  the  junction  of  the  superior  vena  cava  and 
the  right  auricle  is  a  focus  of  tissue  known  as  the  sino-auricular  node 
which  corresponds  to  the  sinus  venosus  of  the  embryo  and  lower 
mammals.  The  special  significance  of  these  structures  will  be 
discussed  later  (see  p.  257). 

Valves. — The  arrangement  of  the  heart's  valves  is  such  that  the 
blood  can  pass  only  in  one 
direction  (fig.  194). 

The  tricuspid  valve  (5,  fig. 
191)  presents  three  principal 
cusps  or  subdivisions,  and  the 
mitral  or  bicuspid  valve  has 
two  such  portions  (6,  fig.  192). 
But  in  both  valves  there  is 
between  each  two  principal 
portions  a  smaller  one :  so 
that  more  properly,  the  tri- 
cuspid may  be  described  as 
consisting  of  six,  and  the 
mitral  of  four,  portions.  Each 
portion  is  of  triangular 
form.  Its  base  is  continu- 
ous with  the  bases  of  the 
neighbouring  portions,  so  as 
to  form  an  annular  mem- 
brane around  the  auriculo- 
ventricular  opening,  and  is 
fixed  to  the  tendinous  ring  which  encircles  the  orifice. 

While  the  bases  of  the  cusps  of  the  valves  are  fixed  to  the 
tendinous  rings,  their  borders  are  fastened  by  slender  tendinous 
fibres,  the  chordce  tendinece,  to  the  internal  surface  of  the  walls 
of  the  ventricles,  the  muscular  fibres  of  which  project  into  the 
ventricular  cavity  in  the  form  of  bundles  or  columns — the  columnce 
carnece.  These  columns  are  not  all  alike,  for  while  some  are  attached 
along  their  whole  length  on  one  side,  and  by  their  extremities,  others 
are  attached  only  by  their  extremities ;  and  a  third  set,  to  which  the 


FIG.  194.— Diagrrm  of  the  circulation  through  the 
heart.    (Dalton.). 


214  THE   CIRCULATORY   SYSTEM  [CH.  XIX. 

name  musculi  papillares  has  been  given,  are  attached  to  the  wall  of 
the  ventricle  by  one  extremity  only,  the  other  projecting,  papilla- 
like,  into  the  cavity  of  the  ventricle  (5,  fig.  192),  and  having  attached 
to  it  chordae  tendineae.  Of  the  tendinous  cords,  besides  those  which 
pass  to  the  margins  of  the  valves,  there  are  some  of  especial  strength, 
which  pass  to  the  edges  of  the  middle  and  thicker  portions  of  the 
cusps.  The  ends  of  these  cords  are  spread  out  in  the  substance  of 
the  valve,  giving  its  middle  part  its  peculiar  strength  and  toughness. 
Moreover,  the  musculi  papillares  are  so  placed  that,  from  the 
summit  of  each,  tendinous  cords  proceed  to  the  adjacent  halves  of 
two  of  the  principal  divisions,  and  to  one  intermediate  or  smaller 
division,  of  the  valve. 

The  preceding  description  applies  equally  to  the  mitral  and 
tricuspid  valve ;  but  it  should  be  added  that  the  mitral  is  considerably 
thicker  and  stronger  than  the  tricuspid,  in  accordance  with  the 
greater  force  which  it  is  called  upon  to  resist. 

The  semilunar  valves  guard  the  orifices  of  the  pulmonary  artery 
and  of  the  aorta.  They  are  nearly  alike  on  both  sides  of  the  heart ; 
but  the  aortic  valves  are  more  strongly  constructed  than  the  pul- 
monary valves,  in  accordance  with  the  greater  pressure  which  they 
have  to  withstand.  Each  valve  consists  of  three  parts  which  are 
of  semilunar  shape,  the  convex  margin  of  each  being  attached  to  a 
fibrous  ring  at  the  place  of  junction  of  the  artery  to  the  ventricle, 
and  the  concave  or  nearly  straight  border  being  free,  so  as  to  form 
a  little  pouch  like  a  watch-pocket  (7,  fig.  192).  In  the  centre  of 
the  free  edge  of  the  pouch,  which  contains  a  fine  cord  of  fibrous 
tissue,  is  a  small  fibrous  nodule,  the  corpus  Arantii,  and  from  this 
and  from  the  attached  border  fine  fibres  extend  into  every  part  of 
the  mid  substance  of  the  valve,  except  a  small  lunated  space  just 
within  the  free  edge,  on  each  side  of  the  corpus  Arantii.  Here 
the  valve  is  thinnest,  and  composed  of  little  more  than  the  endo- 
cardium. Thus  constructed  and  attached,  the  three  semilunar 
pouches  are  placed  side  by  side  around  the  arterial  orifice  of  each 
ventricle ;  they  are  separated  by  the  blood  passing  out  of  the  ventricle, 
but  immediately  afterwards  are  pressed  together  so  as  to  prevent  any 
return.  Opposite  each  of  the  semilunar  cusps,  both  in  the  aorta 
and  pulmonary  artery,  there  is  a  bulging  outwards  of  the  wall  of  the 
vessel :  these  bulgings  are  called  the  sinuses  of  Valsalva. 

Course  of  the  Circulation, 

The  blood  is  conveyed  away  from  the  left  ventricle  (as  in  the 
diagram,  fig.  195)  by  the  aorta  to  the  arteries,  and  returned  to  the 
right  auricle  by  the  veins,  the  arteries  and  veins  being  continuous 
with  each  other  at  the  far  end  by  means  of  the  capillaries. 

From  the  right  auricle  the  blood  passes  to  the  right  ventricle,  then 


CH.  XIX.] 


COURSE   OF   THE   CIRCULATION 


215 


by  the  pulmonary  artery,  which  divides  into  two,  one  for  each  lung, 
then  through  the  pulmonary  capillaries,  and  through  the  pulmonary 
veins  (two  from  each  lung)  to  the  left  auricle.  From  here  it  passes 
into  the  left  ventricle,  which  brings  us  back  to  where  we  started  from. 
The  complete  circulation  is  thus  made  up  of  two  circuits,  the  one, 
a  shorter  circuit  from  the  right  side  of  the  heart  to  the  lungs  and 
back  again  to  the  left  side  of  the  heart ;  the  other  and  longer  circuit, 
from  the  left  side  of  the  heart  to  all  parts  of  the  body  and  back 
again  to  the  right  side.  The  circulations  through  the  lungs  and 
through  the  system  generally  are  respectively  named  the  Pulmonary 


Pulmonary  capillaries. 


Pulmonary  artery. 


Superior  cava  or  vein 
from  head  and  neck. 

Right  auricle. 
Inferior  vena  cava- 

Right  ventricle. 


Portal  circulation. 


Second  renal  circu 
lation. 


Pulmonary  veins. 
Aorta. 

Arteries    to  head  and 
neck. 

Left  auricle. 


Left  ventricle. 


Gastric  and  intestinal 
vessels. 


First  renal  circulation. 


...Systemic  capillarit 


FIG.  105.— Diagram  of  the  circulation. 

and  Systemic  or  lesser  and  greater  circulations.  It  will  be  noticed 
also  in  the  same  figure  that  a  portion  of  the  stream  of  blood  having 
been  diverted  once  into  the  capillaries  of  the  intestinal  canal,  and 
some  other  abdominal  organs,  and  gathered  up  again  into  a  single 
stream,  is  a  second  time  divided  in  its  passage  through  the  liver, 
before  it  finally  reaches  the  heart  and  completes  a  revolution.  This 
subordinate  stream  through  the  liver  is  called  the  Portal  circulation. 
A  somewhat  similar  accessory  circulation  is  that  through  the  kidneys, 
called  the  Renal  circulation.  The  difference  of  colours  in  fig.  195 
indicates  roughly  the  difference  between  arterial  and  venous  blood, 


216 


THE   CIRCULATORY    SYSTEM 


[CH.  XIX. 


The  blood  is  oxygenated  in  the  lungs,  and  the  formation  of  oxy- 
hsemoglobin  gives  to  the  blood  a  bright  red  colour.  This  oxygenated 
or  arterial  blood  (contained  in  the  pulmonary  veins,  the  left  side  of 
the  heart,  and  systemic  arteries)  is  in  part  reduced  in  the  tissues, 
and  the  deoxygenated  haemoglobin  is  darker  in  tint  than  the  oxy- 
haemoglobin ;  this  venous  blood  passes  by  the  systemic  veins  to  the 
right  side  of  the  heart  and  pulmonary  artery  to  the  lungs,  where  it 
once  more  receives  a  fresh  supply  of  oxygen. 

N.B. — It  should,  however,  be  noted  that  the  lungs,  like  the  rest  of  the  body, 
are  also  supplied  with  arterial  blood,  which  reaches  them  by  the  bronchial  arteries. 


The  Arteries. 

The  arterial  system  begins  at  the  left  ventricle  in  a  single  large 
trunk,  the  aorta,  which  almost  immediately  after  its  origin  gives  off 
in  the  thorax  three  large  branches  for  the  supply  of  the  head,  neck, 
and  upper  extremities;  it  then  traverses  the  thorax  and  abdomen, 
giving  off  branches,  some  large  and  some  small,  for  the  supply  of  the 


FIG.  196. — Transverse  section  through  a 
large  branch  of  the  inferior  mesenteric 
artery  of  a  pig.  e,  Endothelial  mem- 
brane ;  i,  tunica  elastica  interna,  no 
subendothelial  layer  is  seen;  m,  mus- 
cular tunica  media,  containing  only  a 
few  wavy  elastic  fibres;  e,  e,  tunica 
elastica  externa,  dividing  the  media 
from  the  connective-tissue  adventitia, 
a.  (Klein  and  Noble  Smith.)  x  350. 


FIG.  197. — Minute  artery 
viewed  in  longitudinal 
section,  e,  Nucleated 
endothelial  membrane, 
Avith  faint  nuclei  in 
lumen,  looked  at  from 
above ;  i,  elastic  mem- 
brane ;  m,  muscular 
coat  or  tunica  media  ; 
a,  tunica  adventitia. 
(Klein  and  Noble 
Smith.)  x  250. 


various  organs  and  tissues  it  passes  on  its  way.  In  the  abdomen  it 
divides  into  two  chief  branches,  for  the  supply  of  the  lower  ex- 
tremities. The  arterial  branches  wherever  given  off  divide  and  sub- 
divide, until  the  calibre  of  each  subdivision  becomes  very  minute,  and 


CH.  XIX.] 


THE   ARTERIES 


217 


these  minute  vessels  lead  into  capillaries.  Arteries  are,  as  a  rule, 
placed  in  situations  protected  from  pressure  and  other  dangers,  and 
are,  with  few  exceptions,  straight  in  their  course,  and  frequently 
communicate  (anastomose  or  inosculate)  with  other  arteries.  The 
branches  are  usually  given  off  at  an  acute  angle,  and  the  sum  of 
the  sectional  areas  of  the  branches  of  an  artery  generally  exceeds 
that  of  the  parent  trunk ;  and  as  the  distance  from  the  origin  is 
increased,  the  area  of  the  combined  branches  is  increased  also. 
After  death,  arteries  are  usually  found  dilated  (not  collapsed  as  the 
veins  are)  and  empty,  and  it  was  to  this  fact  that  their  name 
(aprrjpia,  the  windpipe)  was  given  them,  as  the  ancients  believed  that 
they  conveyed  air  to  the  various  parts  of  the  body.  As  regards 
the  arterial  system  of  the  lungs,  the  pulmonary  artery  is  distributed 
much  as  the  arteries  belonging  to  the  general  systemic  circulation. 

Structure. — The   arterial    wall    is    composed    of    the   following 
coats : — 

(a)  The  external  coat  or  tunica  adventitia  (figs.  196  and  197,  a), 
the  strongest  part  of  the  wall  of  the  artery,  is  formed  of  areolar 
tissue,  with  which  is  mingled  throughout  a  network  of  elastic  fibres. 
At  the  inner  part  of   this  outer  coat   the 

elastic  network  forms,  in  some  arteries,  so 
distinct  a  layer  as  to  be  sometimes  called 
the  external  elastic  coat  (fig.  196,  e). 

(b)  The  middle  coat  (fig.  196,  m)  is  com- 
posed of  both  muscular  and  elastic  fibres, 
with  a  certain  proportion  of  areolar  tissue. 
In  the  larger  arteries  (fig.  196)  its  thickness 
is  comparatively  as  well  as  absolutely  much 
greater  than  in  the  small  ones;  it  consti- 
tutes the  greater  part  of  the  arterial  wall. 
The  muscular  fibres  are  unstriped  (fig.  198), 
and  are  arranged  for  the  most  part  trans- 
versely  to   the   long   axis   of   the    artery; 
while   the   elastic   element,   taking   also   a 
transverse    direction,   is    disposed    in    the 
form  of  closely  interwoven  and  branching 
fibres,  which  intersect  in  all  parts  the  layers 
of  muscular  fibres.     In  arteries  of  various 

sizes  there  is  a  difference  in  the  proportion  of  the  muscular  and 
elastic  element,  elastic  tissue  preponderating  in  the  largest  arteries, 
and  unstriped  muscle  in  those  of  medium  and  small  size. 

(c)  The  internal  coat  is  formed  by  a  layer  of  elastic  tissue,  called 
the  fenestrated  membrane  of  Henle.     Its  inner  surface  is  lined  with  a 
delicate  layer  of  elongated  endothelial  cells  (fig.  196,  e),  which  make 
it  smooth,  so  that  the  blood  may  flow  with  the  smallest  possible 


FIG.  198.— Muscular  fibre-cells 
from  human  arteries,  magni- 
fied 350  diameters.  (Kolliker.) 
a.  Nucleus,  b.  A  fibre-cell 
treated  with  acetic  acid. 


218 


THE   CIRCULATORY   SYSTEM 


[CH.  XIX. 


amount  of  resistance  from  friction.  Immediately  external  to  the 
endothelial  lining  of  the  artery  is  fine  connective  tissue  (sub- 
endothelial  layer)  with  branched  corpuscles.  Thus  the  internal  coat 
consists  of  three  parts,  (a)  an  endothelial  lining,  (5)  the  subendo- 
thelial  layer,  and  (c)  elastic  layer. 

Vasa  Vasorum.  —  The  walls  of  the  arteries  are,  like  other  parts 
of  the  body,  supplied  with  little  arteries,  ending  in  capillaries  and 
veins,  which,  branching  throughout  the  external  coat,  extend  for 
some  distance  into  the  middle,  but  do  not  reach  the  internal  coat. 
These  nutrient  vessels  are  called  vasa  vasorum. 

Nerves.  —  Most  of  the  arteries  are  surrounded  by  a  plexus  of 
sympathetic  nerves,  which  terminate  in  a  plexus  between  the 
muscular  fibres. 


Endothelium. 
Subendothelial  layer. 
Elastic  layer. 


Middle  coat. 


FIG.  199  — Transverse  section  of  aorta  through  the  internal  and  about  half  the  middle  coat. 

The  Veins. 

The  venous  system  begins  in  small  vessels  which  are  slightly 
larger  than  the  capillaries  from  which  they  spring.  These  vessels 
are  gathered  up  into  larger  and  larger  trunks  until  they  terminate 
(as  regards  the  systemic  circulation)  in  the  two  venae  cavae  and  the 


CH.  XIX.] 


THE  VEINS 


219 


Rl 


coronary  veins,  which  enter  the  right  auricle,  and  (as  regards  the 

pulmonary  circulation)  in  four  pulmonary  veins,  which  enter  the  left 

auricle.     The  total  capacity  of  the  veins  diminishes  as  they  approach 

the  heart ;  but,  as  a  rule,  their  capacity  is  two  or  three  times  that 

of  the  corresponding  arteries.      The 

pulmonary    veins,   however,   are    an 

exception  to  this  rule,  as  they  do  not 

exceed    in    capacity    the   pulmonary 

arteries.     The  veins  are  found  after 

death  more  or  less  collapsed,  owing 

to  their  want  of  elasticity.     They  are 

usually  distributed   in   a   superficial 

and  a  deep  set  which  communicate 

frequently  in  their  course. 

Structure. — In  structure  the  coats 
of  veins  bear  a  general  resemblance 
to  those  of  arteries  (fig.  200).  Thus, 
they  possess  outer,  middle,  and  in- 
ternal coats. 

(a)  The  outer  coat  is  constructed 
of  areolar  tissue  like  that  of  the 
arteries,  but  it  is  thicker.  In  some 
veins  it  contains  muscular  fibres, 
which  are  arranged  longitudinally. 

(2>)  The  middle  coat  is  consider- 
ably thinner  than  that  of  the  arteries ; 
it  contains  circular  unstriped  mus- 
cular fibres,  mingled  with  a  few 
elastic  fibres  and  a  large  proportion 
of  white  fibrous  tissue.  In  the  large 
veins,  near  the  heart,  namely,  the 
venae  cavce  and  pulmonary  veins,  the 
middle  coat  is  replaced,  for  some 
distance  from  the  heart,  by  circularly 
arranged  striped  muscular  fibres,  con- 
tinuous with  those  of  the  auricles. 
The  veins  of  bones,  and  of  the  central 
nervous  system  and  its  membranes 
have  no  muscular  tissue. 

(c)  The    internal    coat    of   veins 
membrane,    which    may    be    absent 
endothelium  is  made  up  of  cells  elongated  in  the  direction  of  the 
vessel,  but  wider  than  in  the  arteries. 

Valves. — One   main  distinction  between  arteries  and   veins  is 
the  presence  of  valves  in  the  latter  vessels.     The  general  construc- 


Fio.  200.— Transverse  section  through  a 
small  artery  and  vein  of  the  mucous 
membrane  of  a  child's  epiglottis;  the 
artery  is  thick- walled  and  the  vein  thin- 
walled.  A.  Artery,  the  letter  is  placed 
in  the  lumen  of  the  vessel,  e,  Endo- 
thelial  cells  with  nuclei  clearly  visible ; 
these  cells  appear  very  thick  from  the 
contracted  state  of  the  vessel.  Outside 
it  a  double  wavy  line  marks  the  elastic 
layer  of  the  tunica  intima.  m,  Tunica 
media,  consisting  of  unstriped  muscular 
fibres  circularly  arranged ;  their  nuclei 
are  well  seen,  a,  Part  of  the  tunica 
adventitia  showing  bundles  of  connec- 
tive-tissue fibre  in  section,  with  the 
circular  nuclei  of  the  connective-tissue 
corpuscles.  This  coat  gradually  merges 
into  the  surrounding  connective  tissue, 
v.  In  the  lumen  of  the  vein.  The  other 
letters  indicate  the  same  as  in  the 
artery.  The  muscular  coat  of  the  vein 
(TO)  is  seen  to  be  much  thinner  than 
that  of  the  artery,  x  350.  (Klein 
and  Noble  Smith.) 


has 
in 


a   very   thin 
the    smaller 


fenestrated 
The 


veins. 


220 


THE   CIRCULATORY   SYSTEM 


[CH.  XIX. 


tion  of  these  valves  is  similar  to  that  of  the  semilunar  valves  of  the 
aorta  and  pulmonary  artery,  already  described;  but  their  free  margins 
are  turned  in  the  opposite  direction,  i.e.,  towards  the  heart,  so  as  to 
prevent  any  movement  of  blood  backward.  They  are  commonly 
placed  in  pairs,  at  various  distances  in  different  veins,  but  almost 
uniformly  in  each  (fig.  201).  In  the  smaller  veins  single  valves 


FIG.  201.— Diagram  showing  valves  of  veins.  A,  part  of  a  vein  laid  open  and  spread  out,  with  two  pairs 
of  valves.  B,  longitudinal  section  of  a  vein,  showing  the  apposition  of  the  edges  of  the  valves  in 
their  closed  state.  C,  portion  of  a  distended  vein,  exhibiting  a  swelling  in  the  situation  of  a  pair 
of  valves. 

are    often   met   with;    and    three    or    four  are    sometimes  placed 
together,  or  near   one  another,  in  the  largest  veins,   such  as   the 


FIG.  202.— A,  vein  with  valves  open.    B,  with  valves  closed  ;  stream  of  blood  passing  off  by  lateral 

channel.    (Dalton.) 

subclavian,  at  their  junction  with  the  jugular  veins.     They  are  com- 
posed of  an  outgrowth   of   the  subendothelial   tissue  covered  with 


CH.  XIX. J  THE  VEINS  221 

endothelium.  Their  situation  in  the  superficial  veins  of  the  fore- 
arm is  readily  discovered  by  pressing  along  their  surface,  in  the 
direction  opposite  to  the  venous  current,  i.e.  from  the  elbow  towards 
the  wrist;  when  little  swellings  (fig.  201,  c)  appear  in  the  position 
of  each  pair  of  valves.  These  swellings  at  once  disappear  when  the 
pressure  is  removed. 

Valves  are  not  equally  numerous  in  all  veins,  and  in  many  they 
are  absent  altogether.  They  are  most  numerous  in  the  veins  of  the 
extremities,  and  more  so  in  those  of  the  leg  than  the  arm.  They  are 
commonly  absent  in  veins  of  less  than  a  line  in  diameter,  and,  as  a 
general  rule,  there  are  few  or  none  in  those  which  are  not  subject  to 
muscular  pressure.  Among  those  veins  which  have  no  valves  may 
be  mentioned  the  superior  and  inferior  vena  cava,  the  pulmonary 
veins,  the  veins  in  the  interior  of  the  cranium  and  vertebral  canal, 
the  veins  of  bone,  and  the  umbilical  vein.  The  valves  of  the  portal 
tributaries  are  very  inefficient. 

Lymphatics  of  Arteries  and  Veins. — Lymphatic  spaces  are  present 
in  the  coats  of  both  arteries  and  veins.  In  the  external  coat  of  large 


I-  n..  'J03.- -Surface  view  of  an  artery  from  the  mesentery  of  a  frog,  ensheathed  in  a  perivaseular  lym- 
phatic vessel,  a,  The  artery,  with  its  circular  muscular  coat  (media)  indicated  by  broad  transverse 
markings,  with  an  indication  of  the  adventitia  outside.  I,  Lymphatic  vessel ;  its  wall  is  a  simple 
endothelial  membrane.  (Klein  and  Noble  Sn  ith.) 

vessels  they  form  a  plexus  of  more  or  less  tubular  vessels.     In  smaller 
vessels  they  appear  as  spaces  lined  by  endothelium.     Sometimes,  as 


222  THE  CIRCULATORY  SYSTEM  [CH.  XIX. 

in  the  arteries  of  the  omentum,  mesentery,  membranes  of  the  brain, 
lung,  liver  and  spleen,  the  spaces  are  continuous  with  vessels  which 
distinctly  ensheath  them — perivascular  lymphatics  (fig.  203). 

The  Capillaries. 

In  most  cases  the  blood  finds  its  way  from  the  small  arteries  to 
the  small  veins  through  a  network  of  minute  cylindrical  vessels 
called  capillaries.  But  in  certain  cases  (parathyroid,  spleen,  the 
thyroid  of  some  animals,  erectile  tissue,  the  placenta,  and  the 
embryonic  liver  and  kidney)  the  connecting  system  of  vessels  are 
larger  and  have  an  irregular  shape ;  these  vessels  are  termed  sinusoids. 

The  walls  of  both  capillaries  and  sinusoids  are  composed  of 
endothelium — a  single  layer  of  elongated  flattened  and  nucleated 
cells,  so  joined  and  dovetailed  together  as  to  form  a  continuous 


FIG.  204.— Capillary  blood-vessels  from  the  omentum  of  rabbit,  showing  the  nucleated  endothelial 
membrane  of  which  they  are  composed.    (Klein  and  Noble  Smith.) 

transparent  membrane  (fig.  204).  Here  and  there  the  endothelial 
cells  do  not  fit  quite  accurately;  the  space  is  filled  up  with  cement 
material ;  these  spots  are  called  pseudo-stomata. 

The  diameter  of  the  capillary  vessels  varies  somewhat  in  the 
different  tissues  of  the  body,  the  most  common  size  being  about 
-ooVu-th  °f  an  incn  (12  /x).  Among  the  smallest  may  be  mentioned 
those  of  the  brain,  and  of  the  follicles  of  the  mucous  membrane  of 
the  intestines;  among  the  largest,  those  of  the  skin,  lungs,  and 
especially  those  of  the  medulla  of  bones. 

The  size  of  capillaries  varies  necessarily  in  different  animals  in 
relation  to  the  size  of  their  blood-corpuscles :  thus,  in  the  Proteus, 
the  capillary  circulation  can  just  be  discerned  with  the  naked  eye. 

The  form  of  the  capillary  network  presents  considerable  variety 
in  the  different  tissues  of  the  body :  the  varieties  consist  principally 
of  modifications  of  two  chief  kinds  of  mesh,  the  rounded  and  the 
elongated.  That  kind  in  which  the  meshes  or  interspaces  have  a 


CH.  XIX.] 


LYMPHATIC   VESSELS 


223 


roundish  or  polygonal  form  is  the  most  common,  and  prevails  in 
those  parts  in  which  the  capillary  network  is  most  dense,  such  as 
the  lungs  (fig.  205),  most  glands  and  mucous  membranes,  and  the 
cutis.  The  capillary  network  with  elongated  meshes  is  observed  in 
parts  in  which  the  vessels  are  arranged  among  bundles  of  fine  tubes 
or  fibres,  as  in  muscles  and  nerves.  In  such  parts,  the  meshes  form 
parallelograms  (fig.  206),  the  short  sides  of  which  may  be  from  three 


FIG.  205.— Network  of  capillary 
vessels  of  the  air-cells  of  the 
horse's  lung  magnified,  a,  a, 
Capillaries  proceeding  from  b, 
&,  terminal  branches  of  the 
pulmonary  artery.  (Frey.) 


FIG.  206.— Injected  capil- 
lary vessels  of  muscle 
seen  with  a  low  mag- 
nifying power. 

(Sharpey.) 


to  eight  or  ten  times  less  than  the  long  ones ;  the  long  sides  are 
more  or  less  parallel  to  the  long  axis  of  the  fibres. 

The  number  of  the  capillaries  and  the  size  of  the  meshes  in  different 
parts  determine  in  general  the  degree  of  vascularity  of  those  parts. 
The  capillary  network  is  closest  in  the  lungs  and  in  the  choroid 
coat  of  the  eye. 

It  may  be  held  as  a  general  rule,  that  the  more  active  the 
functions  of  an  organ  are,  the  more  vascular  it  is.  Hence  the 
narrowness  of  the  interspaces  in  all  glandular  organs,  in  mucous 
membranes,  and  in  growing  parts,  and  their  much  greater  width  in 
bones,  ligaments,  and  other  comparatively  inactive  tissues. 


Lymphatic  Vessels. 


The  blood  leaves  the  heart  by  the  arteries  ;  it  returns  to  the  heart 
by  the  veins ;  but  this  last  statement  requires  modification,  for  in  the 
capillaries  some  of  the  blood-plasma  escapes  into  the  cell  spaces  of 
the  tissues  and  nourishes  the  tissue-elements.  This  fluid,  which  is 


224 


THE   CIRCULATORY   SYSTEM 


[CH.  XIX. 


called  lymph,  is  gathered  up  and  carried  back  again  into  the  blood  by 
a  system  of  vessels  called  lymphatics. 

The  principal  vessels  of  the  lymphatic  system  are,  in  structure, 
like  small  thin-walled  veins,  provided  with  numerous  valves.  The 
beaded  appearance  of  the  lymphatic  vessels  shown  in  figs.  208  and 
209  is  due  to  the  presence  of  these  valves.  They  commence  in  fine 
microscopic  lymph-capillaries,  in  the  organs  and  tissues  of  the  body, 


Lymphatics  of  head  and 
neck,  right. 

Right    internal    jugular 

vein. 
Right  subclavian  vein. 


Lymphatics  of  right  arm. 


Receptaculum  chyli. 


Lymphatics  of  lower  ex- 
tremities. 


Lymphatics  of  head  and 
neck,  left. 

Thoracic  duct. 

Left  subclavian  vein. 


Thoracic  duct. 


Lacteals. 


Lymphatics  of  lower  ex- 
tremities. 


FIG.  207. —Diagram  of  the  principal  groups  of  lymphatic  vessels.    (From  Quaiu.) 

and  they  end  in  two  trunks  which  open  into  the  large  veins  near  the 
heart  (fig.  207).  The  fluid  which  they  contain,  unlike  the  blood, 
passes  only  in  one  direction,  namely,  from  the  fine  branches  to  the 
trunk,  and  so  to  the  large  veins,  on  entering  which  it  is  mingled  with 
the  stream  of  blood.  In  fig.  207  the  greater  part  of  the  contents  of 
the  lymphatic  system  of  vessels  will  be  seen  to  pass  through  a  com- 
paratively large  trunk  called  the  thoracic  duct,  which  finally  empties 
its  contents  into  the  blood-stream,  at  the  junction  of  the  internal 


CH.  XIX.] 


LYMPHATIC    VESSELS 


225 


jugular  and  subclavian  veins  of  the  left  side.     There  is  a  smaller 
duct  on  the  right  side.     The  lymphatic  vessels  of  the  intestinal  canal 


FIG.  208. — Lymphatic  vessels  of  the  head  and  neck  and  the 
upper  part  of  the  trunk  (Mascagni).  £. — The  chest  and 
pericardium  have  been  opened  on  the  left  side,  and  the 
left  mamma  detached  and  thrown  outwards  over  the  left 
arm,  so  as  to  expose  a  great  part  of  its  deep  surface.  The 
principal  lymphatic  vessels  and  glands  are  shown  on  the 
side  of  the  head  and  face  and  in  the  neck,  axilla,  and  medi- 
astinum. Between  the  left  internal  jugular  vein  and  the 
common  carotid  artery,  the  upper  ascending  part  of  the 
thoracic  duct  marked  1,  and  above  this,  and  descending 
to  2,  the  arch  and  last  part  of  the  duct.  The  termination 
of  the  upper  lymphatics  of  the  diaphragm  in  the  medias- 
tinal  glands,  as  well  as  the  cardiac  and  the  deep  mammary 
lymphatics,  is  also  shown. 


FIG.  209.— Superficial  lymphatics 
of  the  forearm  and  palm  of 
the  hand.  £.— 5.  Two  small 
glands  at  the  bend  of  the 
arm.  6.  Radial  lymphatic 
vessels.  7.  Ulnar  lymphatic 
vessels.  8,  8'.  Palmar  arch 
of  lymphatics.  9,  9'.  Outer 
and  inner  sets  of  vessels, 
b.  Cephalic  vein,  d,  Radial 
vein,  e,  Median  vein.  /,  Ulnar 
vein.  The  lymphatics  are  re- 
presented as  lying  on  the 
deep  fascia.  (Mascagni.) 


are  called  lacteals,  because  during  digestion  (if  the  meal  contains  fat) 
the  fluid  contained  in  them  resembles  milk  in  appearance ;  and  the 
lymph  in  the  lacteals  during  the  period  of  digestion  is  called  chyle. 


226 


THE  CIRCULATORY  SYSTEM 


[CH.  XIX. 


Chyle  is  lymph  containing  finely  divided  fat-globules.  In  some  parts 
of  its  course  the  lymph-stream  passes  through  lymphatic  glands,  to 
be  described  later  on. 

Origin  of  Lymph  Capillaries. — The  lymphatic  capillaries  com- 
mence most  commonly  either  (a)  in  closely-meshed  networks  (see 
fig.  210),  or  (&)  in  irregular  lacunar  spaces,  lined  by  endothelium, 
between  the  various  structures  of  which  the  different  organs  are 
composed.  These  spaces  freely  communicate  with  the  cell  spaces 
(Saft  Kanalchen,  see  p.  31)  of  the  tissues. 


FIG.  210. — Lymphatics  of  central  tendon  of  rabbit's  diaphragm,  stained  with  silver  nitrate.  The 
shaded  background  is  composed  of  bundles  of  white  fibres,  between  which  the  lymphatics  lie. 
I,  Lymphatics  lined  by  long  narrow  endothelial  cells,  and  showing  v  valves  at  frequent  intervals. 
(Schofield.) 

The  lacteals  offer  an  illustration  of  another  mode  of  origin, 
namely,  as  blind  dilated  extremities  in  the  villi  of  the  small  intestine 
(see  fig.  28,  p.  22). 

The  structure  of  lymphatic  capillaries  is  very  similar  to  that 
of  blood  capillaries ;  their  walls  consist  of  a  single  layer  of  elongated 
endothelial  cells  with  sinuous  outline,  which  cohere  along  their  edges 
to  form  a  delicate  membrane.  They  differ  from  blood  capillaries 
mainly  in  their  larger  and  very  variable  calibre,  in  the  presence  of  valves, 
and  in  their  numerous  communications  with  the  spaces  of  the  tissues. 

In  certain  parts  of  the  body,  stomata  exist,  by  which  lymphatic 
capillaries  directly  communicate  with  parts  formerly  supposed  to  be 
closed  cavities.  They  have  been  found  in  many  serous  membranes ; 
a  serous  cavity  thus  forms  a  large  lymph-sinus  or  widening  out  of 
the  lymph-capillary  system  with  which  it  directly  communicates. 


CHAPTER    XX 

THE   CIRCULATION   OF  THE  BLOOD 

WE  have  now  to  approach  the  physiological  side  of  the  subject, 
and  study  the  means  by  which  the  blood  is  kept  in  movement,  so 
that  it  may  convey  nutriment  to  all  parts,  and  remove  from  those 
parts  the  waste  products  of  their  activity. 

Previous  to  the  time  of  Harvey,  the  vaguest  notions  prevailed 
regarding  the  use  and  movements  of  the  blood.  The  arteries  were 
supposed  by  some  to  contain  air,  by  others  to  contain  a  more  subtle 
essence  called  animal  spirits;  the  animal  spirits  were  supposed  to 
start  from  the  ventricles  of  the  brain,  and  they  were  controlled  by 
the  soul  which  was  situated  in  the  pineal  gland.  How  the  animal 
spirits  got  into  the  arteries  was  an  anatomical  detail  which  was 
bridged  across  by  the  imagination. 

There  was  an  idea  that  the  blood  moved,  but  this  was  considered 
to  be  a  haphazard,  to-and-fro  movement,  and  confined  to  the  veins. 
The  proofs  that  the  movement  is  in  a  -circle  were  discovered  by 
William  Harvey,  and  to  this  eminent  discoverer  also  belongs  the 
credit  of  pointing  out  the  methods  by  which  every  physiological 
problem  must  be  studied.  In  the  first  place  there  must  be  correct 
anatomical  knowledge,  and  in  the  second  there  must  be  experiment, 
by  which  deductions  from  structure  can  be  tested;  moreover,  this 
second  method  is  by  far  the  more  important  of  the  two.  Harvey's 
proofs  of  the  circulation  came  under  both  these  heads.  The  structural 
or  anatomical  facts  upon  which  he  relied  were  the  following : — 

1.  The  existence  of  two  distinct  sets  of  tubes  in  connection  with 
the  heart,  namely,  the  arteries  and  the  veins. 

2.  The  existence  in  the  heart  and  also   in  the  veins,  of  valves 
which  would  only  allow  the  passage  of  the  blood  in  one  direction. 

His  experimental  data  were  the  following: — 

3.  That  the  blood  spurts  with  great  force  and  in  a  jerky  manner 
from  an  artery  opened  during  life,  each  jerk  corresponding  with  a 
beat  of  the  heart. 

4.  That  if  the   large  veins   near   the  heart   are  tied,  the  heart 

227 


228  THE  CIRCULATION   OF  THE  BLOOD  [CH.  XX. 

becomes  pale,  flaccid,  and  bloodless,  and  on  removal  of  the  ligature 
the  blood  again  flows  into  the  heart. 

5.  If  the  aorta  is  tied,  the  heart  becomes  distended  with  blood, 
and  cannot  empty  itself  until  the  ligature  is  removed. 

6.  The  preceding  experiments  were  performed  on  animals,  but  by 
the  following  experiment  he  showed  that  the  circulation  is  a  fact  in 
man  also ;  if  a  ligature  is  drawn  tightly  round  a  limb,  no  blood  can 
enter  it,  and  it  becomes  pale  and  cold.     If  the  ligature  is  somewhat 
relaxed  so  that  blood  can  enter  but  cannot  leave  the  limb,  it  becomes 
swollen.     If  the  ligature  is  removed,  the  limb  soon  regains  its  normal 
appearance. 

7.  Harvey  also  drew  attention  to  the  fact  that  there  is  general 
constitutional  disturbance  resulting  from  the  introduction  of  a  poison 
at  a  single  point,  and  that  this  can  only  be  explained  by  a  movement 
of  the  circulating  fluid  all  over  the  body. 

8.  If   an   artery  is   wounded,   hsemorrhage   may  be   stopped   by 
pressure  applied  between  the  heart  and  the  wound ;  but  in  the  case 
of  a  wound  in  a  vein,  the  pressure  must  be  applied  beyond  the  seat 
of  injury. 

Since  Harvey's  time  many  other  proofs  have  accumulated;  for 
instance : — 

9.  If  a  substance  which,  like  ferrocyanide  of  potassium,  can  be 
readily  detected,  is  injected  at  a  certain  point  into  a  blood-vessel,  it 
will  after  the  lapse  of  a  short  interval  have  entirely  traversed  the 
circulation  and  be  found  in  the  blood  collected  from  the  same  point. 

10.  Perhaps  the  most  satisfactory  proof  of  the  circulation  is  one 
now  within  the  reach  of  every  student,  though  beyond  that  of  Harvey. 
It  consists  in  actually  seeing  the  passage  of  the  blood   from  small 
arteries  through  capillaries   into  veins  in   the  transparent  parts  of 
animals,  such  as  the  tail  of  a  tadpole  or  the  web  of  a  frog's  foot. 
Harvey  could  not  follow  this  part  of  the  circulation,  for  he  had  no 
lenses  sufficiently  powerful  to  enable  him  to  see  it.     Harvey's  idea 
of  the  circulation  here  was  that  the  arteries  carried  the  blood  to  the 
tissues,  which  he  considered  to  be  of  the  nature  of  a  sponge,  and  the 
veins  collected  the  blood  again,  much  in  the  same  way  as  drainage 
pipes  would  collect  the  water  of  a  swamp.     The  discovery  that  the 
ends  of  the  arteries  are  connected  to  the  commencements  of  veins  by 
a  definite  system  of  small  tubes  we  now  call  capillaries,  was  made 
by  Malpighi,  in  the  year  1661.     He  first  observed  them  in  the  tail  of 
the  tadpole,  and  Leeuwenhoek,  seven  years  later,  saw  the  circulation 
in  the  lung  of  the  frog. 

We  can  now  proceed  to  study  some  of  the  principles  on  which 
the  circulation  depends : — 

The  simplest  possible  way  in  which  we  could  represent  the 
circulatory  system  is  shown  in  fig.  211  A.  Here  there  is  a  closed 


CH.  XX.] 


SIMPLE  SCHEMA   OF  CIRCULATION 


229 


ring  containing  fluid,  and  upon  one  point  of  the  tube  is  an  enlarge- 
ment (H)  which  will  correspond  to  the  heart.  It  is  obvious  that  if 
such  a  ring  made  of  an  ordinary  Higginson's  syringe  and  a  tube  were 
placed  upon  the  table,  there  would  be  no  movement  of  the  fluid  in  it ; 
in  order  to  make  the  fluid  move  there  must  be  a  difference  of 
pressure  between  different  parts  of  the  fluid,  and  this  difference  of 
pressure  is  caused  in  the  fluid  by  the  pressure  on  it  of  the  heart 
walls.  If,  for  instance,  one  takes  the  syringe  in  one's  hand  and 
squeezes  it,  one  imitates  a  contraction  of  the  heart :  if  the  syringe 
has  no  valves,  the  fluid  would  pass  out  of  each  end  of  it  in  the 
direction  of  the  two  arrows  placed  outside  the  ring.  When  the 
pressure  on  the  syringe  is  relaxed  (this  would  correspond  to  the 
interval  between  the  heart  beats),  the  fluid  would  return  into  the 
heart  again  in  the  direction  of  the  two  arrows  placed  inside  the  ring. 
This,  however,  would  be  merely  a  to-and-fro  movement,  not  a  circula- 


Fio.  211. — Simple  schema  of  the  circulation. 

tion.  Fig.  211  B  shows  how  this  to-and-fro  movement  could,  by  the 
presence  of  valves,  be  converted  into  a  circulation ;  when  the  heart 
contracts  the  fluid  could  pass  only  in  the  direction  of  the  outer 
arrow;  when  the  heart  relaxes  it  could  pass  only  in  the  direction 
of  the  inner  arrow;  the  direction  of  both  arrows  is  the  same,  and 
so  if  the  contraction  and  relaxation  of  the  heart  are  repeated  often 
enough  the  fluid  will  move  round  and  round  within  the  tubular  ring. 

The  main  factor  in  the  circulation  is  difference  of  pressure.  In 
general  terms  fluid  flows  from  where  the  pressure  is  high  to  where  it 
is  lower.  This  difference  of  pressure  is  produced  in  the  first  instance 
by  the  contraction  of  the  heart,  but  we  shall  find  in  our  study  of  the 
vessels  that  some  of  this  pressure  is  stored  up  in  the  elastic  arterial 
walls,  and  keeps  up  the  circulation  during  the  periods  that  the  heart 
is  resting. 

Coming  to  different  groups  in  the  animal  kingdom  we  may  take 
the  crayfish  or  the  lobster  as  instances  of  animals  which  possess  a 
hsemolymph  system,  that  is,  there  is  no  distinction  between  blood 


230 


THE   CIRCULATION   OF  THE   BLOOD 


[CH.   XX. 


and  lymph.  The  heart  pumps  the  circulating  fluid  along  a  system 
of  vessels  which  distribute  it  over  the  body ;  there  are  no  capillaries, 
and  the  hsemolymph  is  discharged  into  the  tissue  spaces ;  it  is  thence 
drained  into  channels  which  convey  it  to  the  gills,  and  after  it  is 
aerated  there  in  a  set  of  irregular  vessels,  it  is  returned  to  the  peri- 
cardium. It  is  sucked  from  the  pericardium  into  the  heart  during 
diastole,  through  five  small  orifices  in  the  cardiac  wall;  during 
systole  these  are  closed  by  valves.  In  these  animals  the  rate  of  flow 
of  hcemolymph  is  necessarily  slow. 

In  worms,  the  circulatory  system  is  almost  as  simple  as  in  the 

schema  just  described ;  the  heart  is 
a  long  contractile  tube  provided 
with  valves,  which  contracts  peri- 
staltically  and  presses  the  blood 
forwards  into  the  aorta  at  its  an- 
terior end ;  this  divides  into  arteries 
for  the  supply  of  the  body;  the 
blood  passes  through  these  to  capil- 
laries, and  is  collected  by  veins 
which  converge  to  one  or  two  main 
trunks  that  enter  the  heart  at  its 
posterior  end. 

In  fishes,  the  heart  is  divided 
into  a  number  of  chambers  placed 
in  single  file,  one  in  front  of  the 
other;  the  most  posterior  which 
receives  the  veins  is  called  the 
sinus  venosus;  this  contracts  and 
forces  the  blood  into  the  next 
chamber,  called  the  auricle;  this 
forces  the  blood  into  the  next 
cavity,  that  of  the  ventricle,  and 
last  of  all  is  the  aortic  bulb.  From  the  bulb,  branches  pass  to  the 
gills,  where  they  break  up  into  capillaries,  and  the  blood  is  aerated : 
it  then  once  more  enters  larger  vessels  which  unite  to  form  the 
dorsal  aorta,  whence  the  blood  is  distributed  by  arteries  to  all 
parts  of  the  body ;  here  it  passes  into  the  systemic  capillaries,  then 
into  the  veins  which  enter  the  sinus  (whence  we  started)  by  a 
few  large  trunks. 

Taking  the  frog  as  an  instance  of  an  amphibian,  we  find  the 
heart  more  complex,  and  the  simple  peristaltic  action  of  the  heart 
muscle  as  we  have  described  it  in  the  hearts  of  worm  and  fish, 
becomes  correspondingly  modified.  There  is  only  one  ventricle,  but 
there  are  two  auricles,  right  and  left. 

The  ventricle  contains  mixed   blood,  since  it  receives  arterial 


Fro.  212.— The  heart  of  a  frog  (Rana  esculenla) 
from  the  front.  V,  ventricle ;  Ad,  right 
auricle ;  As,  left  auricle  ;  B,  bulbus  arteri- 
osus,  dividing  into  right  and  left  aortse. 
(Bcker.) 


CH.  XX.] 


HEART   OF   FROG 


231 


blood  from  the  left  auricle  (which  is  the  smaller  of  the  two),  and 
venous  blood  from  the  right  auricle ;  the  right  auricle  receives  the 
venous  blood  from  the  sinus,  which  in  turn  receives  it  from  the 
systemic  veins.  The  left 

an     T«ck/->o-iirc»c!  «^.o.o.       <^^^ 

v.p. 

c' 

A.S:- 


s.v: 


--A.Z. 


auricle,  as  in  man,  receives 
the  blood  from  the  pulmon- 
ary veins. 

When  the  ventricle  con- 
tracts, it  forces  the  blood 
onward  into  the  aortic  bulb 
which  divides  into  branches 
on  each  side  for  the  supply 
of  the  head  (fig.  212,  1), 
lungs  and  skin  (fig.  212,  3), 
and  the  third  branch  (fig. 
212,  2),  unites  with  its 
fellow  of  the  opposite  side 
to  form  the  dorsal  aorta  for 

thp    Qnrvnlv    nf    tbp     rp<af    nf 
supply    i 

the  body. 

Passing  from  the  amphi- 
bians to  the  reptiles,  we 
find  the  division  of  the 
ventricle  into  two  beginning,  but  it  is  not  complete  till  we  reach 
the  birds.  The  heart  reaches  its  fullest  development  in  mammals, 
and  we  have  already  described  the  human  as  an  example  of  the 
mammalian  heart.  The  sinus  venosus  is  not  present  as  a  distinct 
chamber  in  the  mammalian  heart  (except  in  a  very  early  foetal  stage), 
but  is  represented  by  that  portion  of  the  right  auricle  at  which  the 
large  veins  enter. 


FIG.  213.— The  heart  of  a  frog  (Rana  esculenta)  from  the 
back,  s.v.,  Sinus  venosus  opened  ;  c.s.s.,  left  vena  cava 
superior;  c.s.d.,  right  vena  cava  superior;  c.i.,  vena 
cava  inferior;  v.p.,  vena  pulmonalis;  A.d.,  right 
auricle  ;  A.s.,  left  auricle  ;  A.p.,  opening  of  communi- 
cation between  the  right  auricle  and  the  sinus  venosus. 
X  2£-3.  (Ecker.) 


CHAPTEE  XXI 

PHYSIOLOGY   OF  THE   HEART 

The  Cardiac  Cycle. 

THE  series  of  changes  which  occurs  in  the  heart  constitutes  the 
cardiac  cycle.  This  must  be  distinguished  from  the  course  of  the 
circulation.  The  term  cycle  indicates  that  if  one  observes  the 
heart  at  any  particular  moment,  the  heart  from  that  moment 
onwards  undergoes  certain  changes  until  it  once  more  assumes  the 
same  condition  that  it  had  at  the  moment  when  the  observation 
commenced,  when  the  cycle  is  again  repeated,  and  so  on.  This 
series  of  changes  consists  of  alternate  contraction  and  relaxation. 
Contraction  is  known  as  systole,  and  relaxation  as  diastole. 

The  contraction  of  the  two  auricles  takes  place  simultaneously, 
and  constitutes  the  auricular  systole ;  this  is  followed  by  the  simul- 
taneous contraction  of  the  two  ventricles,  ventricular  systole,  and 
that  by  a  period  during  which  the  whole  of  the  heart  is  in  a  state  of 
relaxation  or  diastole;  then  the  cycle  again  commences  with  the 
auricular  systole. 

Taking  72  as  the  average  number  of  heart  beats  per  minute,  each 
cycle  will  occupy  TV  of  a  minute,  or  a  little  more  than  0'8  of  a 
second.  This  may  be  approximately  distributed  in  the  following 
way: — 

Auricular  systole  .  about  0*1  +  Auricular  diastole  .  0*7  =  0  '8 
Ventricular  systole  .  ,,  0 '3  +  Ventricular  diastole  .  0'5  =  0'8 
Total  systole  .  .  ,,  0'4  +  Joint  diastole  .  .  0'4  =  0'8 

If  the  speed  of  the  heart  is  quickened,  the  time  occupied  by 
each  cycle  is  diminished,  but  the  diminution  affects  chiefly  the 
diastole.  These  different  parts  of  the  cycle  must  next  be  studied  in 
detail. 

The  Auricular  Diastole. — During  this  time,  the  blood  from  the 
large  veins  is  flowing  into  the  auricles,  the  pressure  in  the  veins 
though  very  low  being  greater  than  that  in  the  empty  auricles.  The 
blood  expands  the  auricles,  and  during  the  last  part  of  the  auricular 


CH.  XXI.]  THE  CARDIAC  CYCLE  233 

diastole  it  passes  on  into  the  ventricles.  The  dilatation  of  the 
auricles  is  assisted  by  the  elastic  traction  of  the  lungs.  The  lungs 
being  in  a  closed  cavity,  the  thorax,  and  being  distended  with  air, 
are  in  virtue  of  their  elasticity  always  tending  to  recoil  and  squeeze 
the  air  out  of  their  interior ;  in  so  doing  they  drag  upon  any  other 
organ  with  which  their  surface  is  in  contact:  this  elastic  traction 
will  be  greatest  when  the  lungs  are  most  distended,  that  is  during 
inspiration,  and  will  be  more  felt  by  the  thin-walled  auricles  than  by 
the  thick -walled  ventricles  of  the  heart. 

The  Auricular  Systole  is  sudden  and  very  rapid ;  by  contracting, 
the  auricles  empty  themselves  into  the  ventricles.  The  contraction 
commences  at  the  entrance  of  the  great  veins,  and  is  thence  pro- 
pagated towards  the  auriculo-ventricular  opening.  The  reason  why 
the  blood  does  not  pass  backwards  into  the  veins,  but  onward  into 
the  ventricles,  is  again  a  question  of  pressure ;  the  pressure  in  the 
relaxed  ventricles,  which  is  so  small  as  to  exert  a  suction  action  on 
the  auricular  blood,  is  less  than  in  the  veins.  Moreover,  the 
auriculo-ventricular  orifice  is  large  and  widely  dilated,  whereas  the 
mouths  of  the  veins  are  constricted  by  the  contraction  of  their 
muscular  coats.  Though  there  is  no  regurgitation  of  the  blood 
backwards  into  the  veins,  there  is  a  stagnation  of  the  flow  of  blood 
onwards  to  the  auricles.  The  veins  have  no  valves  at  their  entrance 
into  the  auricles,  except  the  coronary  vein,  which  does  possess  a 
valve ;  there  are  valves,  however,  at  the  junction  of  the  subclavian 
and  internal  jugular  veins. 

Ventricular  Diastole ;  during  the  last  part  of  the  auricular  diastole 
and  the  whole  of  the  auricular  systole,  the  ventricles  have  been 
relaxed  and  then  filled  with  blood.  The  dilatation  of  the  ventricles 
is  chiefly  brought  about  in  virtue  of  their  elasticity ;  this  is  particu- 
larly evident  in  the  left  ventricle,  with  its  thick  muscular  coat.  It 
is  equal  to  23  mm.  of  mercury,  and  is  quite  independent  of  the 
elastic  traction  of  the  lungs,  which,  however,  in  the  case  of  the 
thinner-walled  right  ventricle  comes  into  play. 

The  Ventricular  Systole ;  this  is  the  contraction  of  the  ventricles, 
and  it  occupies  more  time  than  the  auricular  systole;  when  it 
occurs  the  auriculo-ventricular  valves  are  closed  and  prevent  re- 
gurgitation  into  the  auricles,  and  when  the  force  of  the  systole 
is  greatest,  and  the  pressure  within  the  ventricles  exceeds  that  in  the 
large  arteries  which  originate  from  them,  the  semilunar  valves  are 
opened,  and  the  ventricles  empty  themselves,  the  left  into  the  aorta, 
the  right  into  the  pulmonary  artery.  Each  ventricle  ejects  about 
3  ounces  of  blood  with  each  contraction ;  the  left  in  virtue  of  its 
thicker  walls  acts  much  more  forcibly  than  the  right.  The  greater 
force  of  the  left  ventricle  is  necessary,  as  it  has  to  overcome  the 
resistance  of  the  small  vessels  all  over  the  body ;  whereas  the  right 


234  PHYSIOLOGY  OF  THE   HEART  [CH.  XXI. 

ventricle  has  only  to  overcome  peripheral  resistance  in  the  pulmonary 
district. 

The  shape  of  both  ventricles  during  systole  has  been  described  as  under- 
going an  alteration,  the  diameters  in  the  plane  of  the  base  being  diminished,  and 
the  length  of  the  ventricles  slightly  lessened.  The  whole  heart,  moreover,  moves 
towards  the  right  and  forwards,  twisting  on  its  long  axis  and  exposing  more  of  the 
left  ventricle  anteriorly  than  when  it  is  at  rest.  These  movements,  which  were 
first  described  by  Harvey,  have  been  since  Harvey's  time  believed  to  be  the  cause 
of  the  cardiac  impulse  or  apex  beat  which  is  to  be  felt  in  the  fifth  intercostal 
space  about  three  inches  from  the  middle  line.  It  has,  however,  been  shown  by 
Haycraft  that  these  changes  only  occur  when  the  chest  walls  are  open.  When  the 
heart  contracts  in  a  closed  thorax  it  undergoes  no  rotation,  and  the  contraction  is 
concentric,  that  is,  equal  in  all  directions.  The  diminution  of  the  heart's  volume 
which  occurs  in  systole  cannot  be  the  cause  of  the  apex  beat ;  it  would  rather  tend 
to  draw  the  chest  wall  inwards  than  push  it  outwards. 

The  apex  beat  is  caused  by  two  changes  in  the  physical  condition  of  the  heart. 
In  the  first  place,  on  systole  the  heart  becomes  hard  and  tense,  and  secondly,  its 
attachment  to  the  aorta  becomes  rigid  instead  of  being  flexible  as  it  is  in  diastole. 
Thus,  in  systole,  the  heart  becomes  rigidly  fixed  to  the  aorta,  and,  as  this  vessel  is 
curved,  it  tends  to  open  out  into  a  straight  line,  but  is  prevented  by  the  counter- 
resistance  at  the  two  ends  of  the  arch.  These  are  (a)  the  resistance  of  the  chest 
wall  against  the  heart,  and  (/>)  that  of  the  vertebrae  and  ribs  against  the  thoracic 
aorta.  The  pressure  of  the  heart  against  the  chest  wall  is  confined  to  a  small  area, 
situated  in  the  fifth  intercostal  space,  because  the  heart  surface  is  much  more  curved 
than  the  internal  thoracic  wall.  The  forward  movement  this  pressure  causes  is  the 
apex  beat.  It  must  be  noted  that  this  movement  is  not  over  the  actual  apex  of  the 
heart,  but  is  communicated  from  an  area  on  the  anterior  cardiac  surface. 

Action  of  the  Valves  of  the  Heart. 

1.  The  Auriculo-  Ventricular. — The  distension  of  the  ventricles 
with  blood  continues  throughout  the  whole  period  of  their  diastole. 
The  auriculo- ventricular  valves  are  gradually  brought  into  place  by 
some  of  the  blood  getting  behind  the  cusps  and  floating  them  up ; 
by  the  time  that  the  diastole  is  complete,  the  valves  are  in  appo- 
sition, and  they  are  firmly  closed  by  the  reflux  current  caused 
by  the  systole  of  the  ventricles.  The  diminution  in  the  size  of  the 
auriculo-ventricular  rings  which  occurs  during  systole,  renders  the 
auriculo-ventricular  valves  competent  to  close  these  openings.  The 
margins  of  the  cusps  of  the  valves  are  still  more  secured  in  apposition 
with  one  another,  by  the  simultaneous  contraction  of  the  musculi 
papillares,  whose  chordse  tendineae  have  a  special  mode  of  attachment 
for  this  object.  The  cusps  of  the  auriculo-ventricular  valves  meet 
not  by  their  edges  only,  but  -  by  the  opposed  surfaces  of  their  thin 
outer  borders. 

The  musculi  papillares  prevent  the  auriculo-ventricular  valves 
from  being  everted  into  the  auricle.  For  the  chordae  tendineae  might 
allow  the  valves  to  be  pressed  back  into  the  auricle,  were  it  not  that 
when  the  wall  of  the  ventricle  is  brought  by  its  contraction  nearer 
to  the  auriculo-ventricular  orifice,  the  musculi  papillares  more  than 
compensate  for  this  by  their  own  contraction ;  they  hold  the  cords 


CH.  XXT.]  THE  SOUNDS  OF  THE  HEAKT  235 

tight,  and,  by  pulling  down  the  valves,  add  slightly  to  the  force  with 
which  the  blood  is  expelled. 

These  statements  apply  equally  to  the  auriculo-ventricular  valves 
on  both  sides  of  the  heart ;  the  closure  of  both  is  generally  complete 
every  time  the  ventricles  contract.  But  in  some  circumstances  the 
tricuspid  valve  does  not  completely  close,  and  a  certain  quantity  of 
blood  is  forced  back  into  the  auricle.  This  has  been  called  its  safety- 
valve  action.  The  circumstances  in  which  it  usually  happens  are  those 
in  which  the  vessels  of  the  lung  are  already  completely  full  when  the 
right  ventricle  contracts,  as,  e.g.,  in  certain  pulmonary  diseases,  and 
in  very  active  muscular  exertion.  In  these  cases,  the  tricuspid  valve 
does  not  completely  close,  and  the  regurgitation  of  the  blood  may  be 
indicated  by  a  pulsation  in  the  jugular  veins  synchronous  with  that 
in  the  carotid  arteries. 

2.  The  Semilunar  Valves. — The  commencement;  of  the  ventricular 
systole  precedes  the  opening  of  the  aortic  valves  by  a  fraction  of  a 
second,  as  is  proved  by  examining  records  of  the  intra ventricular  and 
aortic  pressure  curves  taken  simultaneously.  The  first  result  of  the 
contraction  of  the  ventricles  is  the  closure  of  the  auriculo-ventricular 
valves,  and  as  soon  as  this  has  been  effected  the  intra  ventricular 
pressure  begins  to  rise.  It  quickly  reaches  a  point  at  which  it  equals 
the  aortic  pressure,  and  then  exceeds  it,  and  as  soon  as  this  pressure 
differen.ee  has  been  established  the  aortic  valves  are  opened  and  blood 
flows  from  the  ventricle  into  the  aorta.  The  valves  are  kept  open  as 
long  as  the  intra  ventricular  pressure  exceeds  the  aortic,  but  as  soon 
as  the  heart  has  emptied  itself,  the  ventricle  begins  to  relax,  its 
internal  pressure  consequently  begins  to  fall,  and  an  instant  is 
quickly  reached  at  which  it  is  exceeded  by  the  aortic.  The  blood, 
therefore,  tends  to  flow  back  from  the  aorta,  and  in  so  doing  fills  up 
the  pockets  of  the  semilunar  valves,  which  have  always  remained 
partly  filled,  and  brings  them  together  with  a  sharp  movement.  The 
movements  of  the  valves  are  therefore  effected  by  the  occurrence  of 
differences  of  pressure  upon  their  two  faces.  When  they  meet  they 
completely  close  the  orifice,  because  their  inner  edges,  which  are 
thinner  than  the  rest  of  the  valves,  are  brought  into  apposition 
and  held  so  by  the  high  pressure  acting  on  their  aortic  surfaces 
only. 

The  Sounds  of  the  Heart. 

When  the  ear  is  placed  over  the  region  of  the  heart,  two  sounds 
may  be  heard  at  every  beat  of  the  heart,  which  follow  in  quick 
succession,  and  are  succeeded  by  a  pause  or  period  of  silence.  The 
first  or  systolic  sound  is  dull  and  prolonged;  its  commencement 
coincides  with  the  impulse  of  the  heart  against  the  chest  wall,  and 
it  lasts  during  the  greater  part  of  the  ventricular  systole;  it 


236 


PHYSIOLOGY   OF   THE   HEART 


[CH.  XXI. 


just  precedes  the  pulse  at  the  wrist.  The  second  or  diastolic  sound 
is  shorter  and  sharper,  with  a  somewhat  flapping  character,  and 
follows  the  end  of  ventricular  systole,  and  is  audible  just  after  the 
radial  pulse  is  felt.  The  sounds  are  often  but  somewhat  inaptly 
compared  to  the  syllables,  lull — dup. 

Causes. — The  exact  cause  of  the  first  sound  of  the  heart  is  a 
matter  of  discussion.  Two  factors  probably  enter  into  it,  viz.,  first, 
the  miration  of  the  auriculo-ventricular  valves  and  the  chordae  tendinece. 
This  vibration  is  produced  by  the  increased  intraventricular  pressure 
set  up  when  the  ventricular  systole  commences,  which  puts  the  valves 
on  the  stretch.  It  is  not  unlikely,  too,  that  the  vibration  of  the 
ventricular  walls  themselves,  and  of  the  aorta  and  pulmonary  artery, 

all  of  which  parts  are  suddenly 
put  into  a  state  of  tension  at 
the  moment  of  ventricular  con- 
traction, may  have  some  part 
in  producing  the  first  sound. 
The  second  factor  is  a  muscular 
sound  produced  by  contraction 
of  the  mass  of  muscular  fibres 
which  forms  the  ventricle. 
Looking  upon  the  contraction  of 
the  heart  as  a  single  contraction 
and  not  as  a  series  of  contrac- 
tions or  tetanus,  it  is  at  first 
sight  difficult  to  see  why  there 
should  be  any  muscular  sound 
at  all  when  the  heart  contracts, 
as  a  single  muscular  contraction 
does  not  produce  sound.  It  has 
been  suggested,  however,  that 
it  arises  from  the  repeated  unequal  tension  produced  when  the  wave 
of  muscular  contraction  passes  along  the  very  intricately  arranged 
fibres  of  the  ventricular  walls.  Many  regard  the  valvular  element  as 
the  more  important  of  the  two  factors,  because  the  sound  is  loudest 
at  first,  when  the  vibration  of  the  valves  commences,  and  fades 
away  as  the  vibrations  cease.  If  the  sound  was  mainly  muscular, 
it  would  be  loudest  when  the  muscular  contraction  was  most  powerful, 
which  is  approximately  about  the  middle  of  the  ventricular  systole. 
The  facts  of  disease  lend  support  to  the  theory  that  the  first  sound 
is  mainly  valvular ;  for  when  the  valves  are  incompetent,  the  first 
sound  is  largely  replaced  by  a  murmur  due  to  regurgitation  of  blood 
into  the  auricle.  After  the  removal  of  the  heart  from  the  body,  the 
muscular  contribution  to  the  first  sound  is  audible,  but  it  is  very  faint. 
It  is  stated  to  have  a  somewhat  lower  pitch  than  the  valvular  sound. 


CH.  XXI.]  THE   CORONARY  ARTERIES  237 

There  is,  on  the  other  hand,  much  to  be  said  against  the 
view  that  the  cause  of  the  first  sound  is  entirely  due  to  vibra- 
tion of  the  auriculo  -  ventricular  valves.  Any  sound  produced 
by  the  valves  must  be  very  quickly  damped  by  the  high  pressure 
acting  on  their  ventricular  surfaces  only.  The  sustained  character 
of  the  sound  (throughout  practically  the  whole  of  the  ventricular 
systole)  is  on  the  other  hand  exactly  what  is  to  be  expected  if  it  is 
of  muscular  origin.  The  argument  that  the  extent  to  which  the 
muscle  sound  contributes  to  the  production  of  the  first  sound  can 
be  judged  from  the  sound  heard  in  an  isolated  and  empty  heart  is 
quite  fallacious,  since  under  these  conditions  the  muscle  is  contract- 
ing against  no  resistance. 

The  cause  of  the  second  sound  is  more  simple  than  that  of  the 
first.  It  is  entirely  due  to  the  vibration  consequent  on  the  sudden 
stretching  of  the  semilunar  valves  when  they  are  pressed  down  across 
the  orifices  of  the  aorta  and  pulmonary  artery.  The  influence  of 
these  valves  in  producing  the  sound  was  first  demonstrated  by  Hope, 
who  experimented  with  the  hearts  of  calves.  In  these  experiments 
two  delicate  curved  needles  were  inserted,  one  into  the  aorta,  and 
another  into  the  pulmonary  artery,  below  the  line  of  attachment  of 
the  semilunar  valves,  and,  after  being  carried  upwards  about  half  an 
inch,  were  brought  out  again  through  the  coats  of  the  respective 
vessels,  so  that  in  each  vessel  one  valve  was  included  between  the 
arterial  walls  and  the  wire.  Upon  applying  the  stethoscope  to  the 
vessels,  after  such  an  operation,  the  second  sound  ceased  to  be 
audible.  Disease  of  these  valves,  when  sufficient  to  interfere  with 
their  efficient  action,  also  demonstrates  the  same  fact  by  modifying 
the  second  sound  or  destroying  its  distinctness. 

The  contraction  of  the  auricles  is  inaudible. 

The  first  sound  is  heard  most  distinctly  at  the  apex  beat  in  the 
fifth  interspace ;  the  second  sound  is  best  heard  over  the  second  right 
costal  cartilage — that  is,  the  place  where  the  aorta  lies  nearest  to 
the  surface.  The  pulmonary  and  aortic  valves  generally  close  simul- 
taneously. In  some  cases,  however,  the  aortic  may  close  slightly 
before  the  pulmonary  valves,  giving  rise  to  a  "  reduplicated  second 
sound."  The  pulmonary  contribution  to  this  sound  is  best  heard  over 
the  second  left  cartilage. 

The  Coronary  Arteries. 

The  coronary  arteries  are  the  first  branches  of  the  aorta;  they 
originate  from  the  sinuses  of  Valsalva,  and  are  destined  for  the  supply 
of  the  heart  itself ;  the  entrance  of  the  coronary  vein,  into  the  right 
auricle,  we  have  already  seen  (p.  209). 

Ligature    of    the   coronary   arteries    causes    almost    immediate 


238  PHYSIOLOGY   OF   THE   HEART  [CH.  XXI. 

death ;  the  heart,  deprived  of  its  normal  blood-supply,  beats  irregu- 
larly, goes  into  fibrillary  twitchings,  and  then  ceases  to  contract 
altogether. 

In  fatty  degeneration  of  the  heart  in  man,  sudden  death  is  by 
no  means  infrequent.  This  is  in  many  cases  due  to  a  growth  in 
thickness  of  the  walls  of  the  coronary  arteries  called  atheroma,  which 
progresses  until  the  lumen  of  these  arteries  is  obliterated,  and  the 
man  dies  almost  as  if  they  had  been  ligatured. 

Self-steering  Action  of  the  Heart. — This  expression  was  originated  by  Briicke. 
He  supposed  that  the  serailunar  valves  closed  the  orifices  of  the  coronary  arteries 
during  the  systole  of  the  heart.  Unlike  all  the  other  arteries  of  the  body,  the 
coronary  arteries  would  therefore  fill  only  during  diastole,  and  this  increased  fulness 
of  the  vessels  in  the  heart  walls  during  diastole  would  assist  the  ventricle  to  dilate. 
This,  however,  is  incorrect ;  the  valves  do  not  cover  the  mouths  of  the  arteries ;  and 
at  the  beginning  of  systole  the  velocity  and  pressure  in  the  coronary  arteries 
increase  ;  but  later  on  during  systole  the  ventricular  wall  is  so  strongly  contracted 
that  the  muscular  tension  becomes  greater  than  the  coronary  pressure,  and  so  the 
coronary  arteries  and  their  branches  are  compressed,  and  the  blood  driven  back 
into  the  aorta;  the  coronary  arteries  are  then  again  filled  with  the  commencing 
diastole.  Self-steering  action  of  the  heart  therefore  exists,  but  it  is  brought  about  in 
a  different  way  from  what  Briicke  supposed. 

Cardiographs. 

A  cardiograph  is  an  instrument  for  obtaining  a  graphic  record 
of  the  heart's  movements.  In  animals  the  heart  may  be  exposed, 
and  levers  connected  to  its  various  parts  may  be  employed  to 
write  on  a  revolving  blackened  surface. 

A  simple  instrument  for  the  frog's  heart  is  the  following : — 

\F 


FIG.  215.— Simple  Cardiograph  for  frog's  heart. 

The  sternum  of  the  frog  having  been  removed,  the  pericardium 
opened,  and  the  fraenum  (a  small  band  from  the  back  of  the  heart 
to  the  pericardium)  divided,  the  heart  is  pulled  through  the  open- 
ing, a  minute  hook  placed  in  its  apex,  and  this  is  fixed  by  a  silk 
thread  to  a  lever  pivoted  at  F  as  in  the  figure.  The  cardiac  wave 
of  contraction  starts  at  the  sinus,  this  is  followed  by  the  auricular 
systole,  and  that  by  the  ventricular  systole  and  pause.  This  is 


CH.  XXL] 


CARDIOGRAPHS 


239 


recorded  as  in  the  next  figure  (fig.  216)  by  movements  of  the  writing 
point  at  the  end  of  the  long  arm  of  the  lever.  Such  apparatus  is, 
however,  not  applicable  to  the  human 
heart,  and  all  the  various  forms  of  cardio- 
graph devised  for  this  purpose  are  modi- 
fications of  Marey's  tambours.  One  of 
those  most  frequently  used  is  depicted  in 
the  next  two  diagrams. 


It  (fig.  217)  consists  of  a  cup-shaped  metal  box 
over  the  open  front  of  which  is  stretched  an  elastic 
india-rubber  membrane,  upon  which  is  fixed  a  small 
knob  of  hard  wood  or  ivory.  This  knob,  however, 
may  be  attached,  as  in  the  figure,  to  the  side  of  the 
box  by  means  of  a  spring,  and  may  be  made  to  act 
upon  a  metal  disc  attached  to  the  elastic  membrane. 

The  knob  is  for  application  to  the  chest  wall 
over  the  apex  beat.  The  box  or  tambour  communi- 
cates by  means  of  an  air-tight  tube  with  the  interior 
of  a  second  tambour,  in  connection  with  which  is  a 
long  and  light  lever.  The  shock  of  the  heart's 
impulse  being  communicated  to  the  ivory  knob  and 

through  it  to  the  first  tambour,  the  effect  is  at  once  transmitted  by  the  column 
of  air  in  the  elastic  tube  to  the  interior  of  the  second  tambour  (fig.  218),  also  closed, 
and  through  the  elastic  and  movable  lid  of  the  latter  to  the  lever,  which  is  placed  in 
connection  with  a  registering  apparatus,  which  consists  of  a  cylinder  covered  with 

Tube  to  communicate 
with  tambour. 


FIG.  216. — Cardiogram  of  frog's 
heart  C,  showing  auricular, 
followed  by  ventricular  beat; 
T,  time  in  half  seconds. 


Tambour. 


Ivory    Tape  to  attach  the  instru- 
knob.  ment  to  the  chest. 


FIG.  217. — Cardiograph.    (Sanderson's.) 

smoked  paper,  revolving  with  a  definite  velocity.  The  point  of  the  lever  writes 
upon  the  paper,  and  a  tracing  of  the  heart's  impulse  or  cardiogram  is  thus 
obtained. 


Fig.  219  represents  a  typical  tracing  obtained  in  this  way.  The 
first  small  rise  of  the  lever  is  caused  by  the  auricular,  the  second 
larger  rise  by  the  ventricular  systole ;  the  downstroke  represents  the 


240 


PHYSIOLOGY   OF  THE   HEAKT 


[CH.  XXL 


pause,  the  tremors  at  the  commencement  of  which  are  partly  instru- 
mental and  partly  caused  by  the  closure  of  the  semilunar  valves. 


Screw  to  regulate  elevation  of  lever. 


Writin 


lever. 


I 

Tambour. 


Tube  of  cardiograph. 


FIG.  218.— Marey's  Tambour,  to  which  the  movement  of  the  column  of  air  in  the  first  tambour  is  con- 
ducted by  a  tube,  and  from  which  t  is  communicated  by  the  lever  to  a  revolving  cylinder,  so  that 
the  tracing  of  the  movement  of  the  impulse  beat  is  obtained. 

Another  method  of  obtaining  a  tracing  from  one's  own  heart 
consists  in  dispensing  with  the  first  tambour,  and  placing  the  tube 
of  the  recording  tambour  in  one's  mouth,  and  holding  the  breath 


FIG.  219.— Cardiogram  from  human  heart.    The  variations  in  the  individual  beats  are  due  to  the 
^.influence  of  the  respiratory  movements  on  the  heart.    To  be  read  from  left  to  right. 

though  keeping  the  glottis  open.  The  chest  then  acts  as  the  first 
tambour,  and  the  movements  of  the  lever  (cardio-pneumatogram)  may 
be  written  in  the  usual  way. 

Intracardiac  Pressure. 

The  tracings  of  the  cardiograph  are,  however,  very  variable,  and 
their  interpretation  is  a  matter  of  discussion.  A  much  better  method 
of  obtaining  a  graphic  record  of  the  events  of  the  cardiac  cycle  con- 
sists in  connecting  the  interior  of  an  animal's  heart  with  recording 
apparatus.  There  are  several  methods  by  which  the  intracardiac 
pressure  may  be  recorded. 

By  placing  two  small  india-rubber  air-bags  or  cardiac  sounds  down 
the  jugular  vein  into  the  interior  respectively  of  the  right  auricle  and 
the  right  ventricle,  and  a  third  in  an  intercostal  space  in  front  of  the 
heart  of  a  living  animal  (horse),  and  placing  these  bags,  by  means  of 


CH.  XXI.] 


INTKACAilDIAC    PEESSURE 


241 


long  narrow  tubes,  in  communication  with  three  tambours  with 
levers,  arranged  one  over  the  others  in  connection  with  a  registering 
apparatus  (fig.  220),  Chauveau  and  Marey  were  able  to  record  and 


FIG. 


).— Apparatus  of  MM.  Chauveau  and  Marey  for  estimating  the  variations  of  endocardiac 
pressure,  and  the  production  of  the  impulse  of  the  heart. 


measure  the  variations  of  the  intracardiac  pressure  and  the  compara- 
tive duration  of  the  contractions  of  the  auricles  and  ventricles.  By 
means  of  the  same  apparatus,  the  synchronism  of  the  impulse  with 
the  contraction  of  the  ventricles  is  also  shown. 

In  the  tracing  (fig.  221),  the  inter- 
vals between  the  vertical  lines  represent 
periods  of  a  tenth  of  a  second.  The 
parts  on  which  any  given  vertical  line 
falls  represent  simultaneous  events.  It 
will  be  seen  that  the  contraction  of  the 
auricle,  indicated  by  the  marked  curve 
at  A  in  the  first  tracing,  causes  a  slight 
increase  of  pressure  in  the  ventricle, 
which  is  shown  at  A'  in  the  second 
tracing,  and  produces  also  a  slight  im- 
pulse, which  is  indicated  by  A"  in  the 
third  tracing.  The  large  curve  of  the 
ventricular  and  the  impulse  tracings, 
between  A'  and  D',  and  A"  and  D",  are 
caused  by  the  ventricular  contraction ; 
while  the  smaller  undulations,  between 
B  and  c,  B'  and  c',  B"  and  c",  are  caused 
by  the  vibrations  consequent  on  the  tightening  and  closure  of  the 
auriculo-ventricular  valves. 

Much  objection  has,  however,  been  taken  to  this  method  of 
investigation.  First,  because  it  does  not  admit  of  both  positive 
and  negative  pressure  being  recorded.  Secondly,  because  the  method 

Q 


FIG.  221.— Tracings  of  (1),  Intra-auricular, 
and  (2),  Intraventricular  pressure, 
and  (3),  of  the  impulse  of  the  heart; 
to  be  read  from  left  to  right;  ob- 
tained by  Chauveau  and  Marey's 
apparatus. 


242 


PHYSIOLOGY   OF   THE   HEART 


[CH.  XXI. 


is  only  applicable  to  large  animals,  such  as  the  horse.  Thirdly, 
because  the  intraventricular  changes  of  pressure  are  communicated 
to  the  recording  tambour  by  a  long  elastic  column  of  air ;  and 
fourthly,  because  the  tambour  arrangement  has  a  tendency  to  record 
inertia  vibrations.  Kolleston  reinvestigated  the  subject  with  a  more 
suitable  but  rather  complicated  apparatus.  The  principle  of  his 
method  consisted  in  placing  the  cavity  of  a  heart-chamber  in 
communication  with  a  recording  apparatus  by  means  of  a  tube 
containing  saline  solution.  His  recording  apparatus  consisted  of  a 
lever  connected  to  a  piston ;  the  upward  and  downward  movements 
of  the  piston-rod  were  due  to  the  varying  pressures  exerted  on  the 
blood  by  the  contraction  and  dilatation  of  the  heart. 

Another  and  still  better  method  of  overcoming  the  imperfections 
of  Marey's  tambour  is  by  the  use  of  Hurthle's  manometer  (fig.  222). 


FIG.  222.— Hurthle's  Manometer. 

In  this  the  tambour  is  very  small,  the  membrane  is  made  of  -thick 
rubber,  and  the  whole,  including  the  tube  that  connects  it  to  the 
heart,  is  filled  with  a  strong  saline  solution  (saturated  solution  of 
sodium  sulphate). 

The  tracing  obtained  by  this  instrument,  when  connected  with 
the  interior  of  the  ventricle,  is  represented  in  the  next  figure. 


FIG.  223. — Curve  of  intraventricular  pressure.    (After  Hiirthle.) 

The  auricular  systole  causes  a  small  rise  of  pressure  (A  B)  ;  it  lasts 
about  *05  second.  It  is  immediately  followed  by  the  ventricular  con- 
traction, which  lasts  from  B  to  D.  From  B  to  c  the  ventricle  is 
getting  up  pressure,  so  that  at  C  it  equals  the  aortic  pressure.  This 
takes  '02  to  '04  second.  Just  beyond  c  the  aortic  valves  open,  and 
blood  is  driven  into  the  aorta ;  the  outflow  lasts  from  c  to  D  ('2 
second).  At  D  the  ventricle  relaxes.  The  flat  top  of  the  curve  is 
spoken  of  as  the  systolic  plateau,  and  according  to  the  state  of  the 


CH.  XXI.]  THE  ELECTRO -CARDIOGK AM  243 

heart  and  the  peripheral  resistance  may  present  a  gradual  ascent  or 
descent ;  it  occupies  about  18  second.  Almost  immediately  after  the 
relaxation  begins  the  intraventricular  pressure  falls  below  the 
aortic,  so  that  the  aortic  valves  close  near  the  upper  part  of  the 
descent  at  E. 

The  actual  amount  of  pressure  in  the  heart  is  measured  by  a 
mercurial  manometer,  which  is  connected  to  the  heart  by  a  tube  con- 
taining a  valve.  This  was  first  used  by  Goltz  and  Gaule.  If  the  valve 
permits  fluid  to  go  only  from  the  heart,  the  manometer  will  indicate 
the  maximum  pressure  ever  attained  during  the  cycle.  If  it  is 
turned  the  other  way,  it  will  indicate  the  minimum  pressure.  The 
following  are  some  of  the  measurements  taken  from  the  dog's  heart 
in  terms  of  millimetres  of  mercury : — 

Maximum  Minimum 

pressure.  pressure. 

Left  ventricle  .  .  .140  ram.  -  30  to  40  mm. 

Right  ventricle  .  .  .60  mm.  - 15  mm. 

Right  auricle .  .  .  .20  mm.  -    7  to  8  mm. 

By  a  negative  ( — )  pressure  one  means  a  pressure  less  than  that  of 
the  atmosphere,  so  that  the  mercury  is  sucked  up  in  the  limb  of  the 
manometer  towards  the  heart. 

Another  valuable  instrument  introduced  by  Hiirthle  is  called  the  differential 
manometer.  In  this  instrument,  two  cannulae  are  brought  into  connection  with 
tambours  (A  and  u)  which  work  on  points  of  a  lever  at  equal  distances  from  and  on 


B  A 

FIG.  '224.— Diagram  of  Hiirthle's  differential  Manometer. 

opposite  sides  of  its  fulcrum  (r).  The  lever  sets  in  motion  a  writing  style  (s).  This 
instrument  enables  us  to  determine  the  relations  of  the  pressure  changes  in  any 
two  cavities.  For  instance,  suppose  A  is  connected  to  the  left  ventricle,  and  B  to 
the  aorta  ;  when  the  pressure  in  the  ventricle  is  greater  than  that  in  the  aorta,  the 
writing  style  will  be  raised ;  when  the  pressure  in  the  aorta  is  greater  than  that  in 
the  ventricle,  the  style  will  fall ;  when  the  two  pressures  are  equal,  it  will  be  in  the 
zero  position. 

The  Electro-Cardiogram. 

The  muscular  tissue  of  the  heart  gives  rise  on  action  to  an 
electrical  disturbance  which  is  in  all  essential  features  the  same 
as  the  diphasic  variation  we  have  already  studied  in  Chapter  XI. 
in  connection  with  voluntary  muscle.  The  excised  beating  heart 
of  a  frog  can  be  readily  connected  either  to  a  galvanometer  or 


244 


PHYSIOLOGY   OF   THE   HEART 


[CH.  XXI. 


electrometer,  and  the  different  phases  of  the  action  current  can  in 
the  former  case  be  ascertained  by  watching  the  movements  of  the 
magnetic  needle,  and  in  the  latter  case  by  watching  under  the 
microscope  the  movements  of  the  meniscus  of  mercury  in  the  capil- 
lary tube.  If  the  eyepiece  of  the  microscope  is  removed,  and  the 
image  of  the  mercurial  column  allowed  to  fall  on  a  moving  photo- 
graphic plate,  a  graphic  record  is  obtained,  in  which  the  to-and-fro 
movements  of  the  mercury  are  shown  as  waves.  Such  a  graphic 
record  is  termed  an  electro-cardiogram,  and  one  of  these  is  shown 
in  the  next  figure  (fig.  225). 


FIG.  '225. — Electrocardiogram  from  frog's  ventricle.  Diphasic  variation.  (Simultaneous  photograph 
of  a  single  beat  (upper  black  line),  and  the  accompanying  electrical  change  indicated  by  the  level 
of  the  black  area,  which  shows  the  varying  level  of  mercury  in  a  capillary  electrometer.  The  time- 
tracing  at  the  top  marks  tenths  of  a  second.  (Waller.) 

It  is,  however,  possible  (as  Waller  first  demonstrated)  to  obtain 
an  electro- cardiogram  in  the  intact  animal,  and  even  in  man.  If  a 
dog  is  placed  with  a  fore  paw  in  a  basin  of  salt  solution,  and  a  hind 
paw  in  another,  and  the  two  basins  are  led  off  to  the  electrometer, 
the  electrical  changes  produced  by  the  beating  heart  will  be  con- 
ducted through  the  body  of  the  animal  and  through  the  electrometer, 
and  the  movements  of  the  mercury  can  be  watched  with  a  microscope 
or  recorded  on  a  travelling  photographic  plate.  By  the  use  of  this 
method  Miss  Buchanan  has  succeeded  in  performing  what  otherwise 
would  have  been  the  impossible  task  of  counting  the  heart  rate  of 
small  mammals  such  as  mice.  The  photographic  plate  must  travel 
at  great  speed,  and  the  notches  in  the  shadow  of  the  mercurial 
column,  which  correspond  to  the  heart-beats,  were  found  in  the 
mouse  to  occur  at  the  rate  of  700  per  minute.  In  a  corresponding 
way  the  human  electro-cardiogram  can  be  registered,  as  shown  in 
fig.  226.  In  that  particular  experiment,  the  "lead-offs"  were  from 
mouth  and  left  foot.  It  is  more  usual  to  employ  one  hand  and 
one  foot. 

We  must,  however,  recognise  that  the  heart  muscle  is  not  a 
simple  longitudinal  strip  like  a  sartorius,  but  is  arranged  in  a  com- 
plex way,  and  in  the  mammalian  heart  is  arranged  around  four 


CH.  XXL] 


THE   ELECTRO-CARDIOGRAM 


245 


chambers,  and  that  the  left  and  right  sides  are  contracting 
simultaneously.  One  would  therefore  anticipate  that  there  would 
be  a  corresponding  complexity  in  the  electrical  record  of  the  intact 
organ.  This  expectation  has  been  verified  by  later  work  in  which 
investigators  have  used  more  sensitive  instruments.  But  there  was 
some  indication  of  this  even  in  the  records  of  the  earlier  workers 
who  employed  the  capillary  electrometer.  Thus  Bayliss  and 
Starling  described  in  the  mammalian  heart  a  triphasic  variation, 
and  Gotch  by  means  of  careful  experiments  on  both  cold  and  warm 
blooded  animals,  has  shown  that  this  is  explicable  in  the  following 


FIG.  226. — Human  heart.  Electro-cardiogram,  EE,  and  simultaneous  cardiogram,  CC.  Time,  tt,  is 
marked  in  ^th  second.  The  lead-offs  to  the  capillary  electrometer  were  from  the  mouth  to  the 
sulphuric  acid,  and  from  the  left  foot  to  the  mercury.  (Waller.) 

way.  Leaving  out  of  account  complications  due  to  auricular 
activity,  he  has  shown  that  the  contraction  process  in  each  ventricle 
and  its  electrical  concomitant  commences  at  the  part  of  the  base  of 
the  ventricle  where  it  is  continuous  with  its  respective  auricle ;  the 
contraction  wave  travels  to  the  apex  and  returns  to  the  part  of  the 
base  from  which  the  aorta  on  one  side  and  the  pulmonary  artery  on 
the  other  side  arise.  An  electrode  placed  on  the  base  will  therefore 
record  the  increased  positivity  at  the  beginning  and  the  end  of  the 
ventricular  contraction;  the  electrode  on  the  apex  will  record  the 
middle  phase  when  the  contraction  wave  reaches  that  point,  and 
causes  an  increase  of  positivity  there. 

By  far  the  most  delicate  instrument  now  in  use  is  Einthoven's 
String  Galvanometer  (see  p.  121),  and  during  the  last  few  years  it 
has  been  much  employed,  not  only  by  Einthoven  himself,  but  by 
numerous  other  observers,  including  Dr  T.  Lewis,  in  this  country. 
The  excursions  of  the  thread  or  string  can  be  photographed,  and  the 
following  diagram  is  a  cardio-electrogram  obtained  from  the  human 
heart  during  a  single  beat,  the  electrodes  being  connected  with  the 
right  and  left  hands. 

It  will  be  seen  that  there  is  a  small  movement  due  to  the 
auricular  systole,  and  several  large  ones  which  accompany  ventricular 
contraction.  The  exact  meaning  of  these  different  waves  is  still  far 


246  PHYSIOLOGY  OF  THE  HEART  [CH.  XXL 

from  clear,  and  the  extent  of  each  varies  considerably  even  in  health, 
but   in    heart   disease   the   electro-cardiogram   shows    very   marked 
differences  from   the   normal,  especially  in  cases  of  "heart-block." 
When  in  the  future  the  meaning  of  each  part  of  the  record  is  under 
stood,  the  physician  will  be  provided  with  a  new  help  to  diagnosis. 


FIG.  227.— Electro-cardiogram  obtained  by  photographing  the  movements  of  the  thread  of  a  String 
Galvanometer.  The  electrodes  were  connected  to  a  man's  right  and  left  hands.  Waves  upwards 
indicate  that  the  base  (right  ventricle)  is  galvanometrically  negative  to  the  apex  (left  ventricle) ; 
downward  waves  have  the  opposite  meaning.  Wave  P  accompanies  auricular  systole ;  waves 
Q,  R,  S,  and  T  occur  during  ventricular  systole.  The  time- tracing  (T)  shows  tenths  of  a  second. 
(After  Einthoven.) 

The  Cardiophonogram. — An  interesting  extension  of  this  work 
consists  in  the  registration  of  the  heart  sounds.  This  was  first  done 
by  Hiirthle  some  years  ago,  but  Einthoven's  string  galvanometer,  as 
an  instrument  of  precision  far  exceeding  these  previously  used, 
has  enabled  him  to  repeat  this  work  with  much  greater  accuracy.  A. 
stethoscope  is  placed  over  the  chest  and  connected  to  a  microphone, 
which  magnifies  the  heart  sounds ;  the  vibrations  in  the  microphone 
are  communicated  as  electrical  changes  by  a  transformer  to  the 
string  galvanometer,  the  movements  of  the  quartz  fibre  being  finally 
photographed  on  a  travelling  plate.  If  simultaneously  an  electro- 
cardiogram is  taken,  the  simultaneity  of  the  first  heart  sound  with 
the  ventricular  systole,  and  of  the  second  heart  sound  with  the  com- 
mencement of  ventricular  diastole,  are  very  conclusively  demon- 
strated. In  heart  disease  where  the  adventitious  sounds  called 
murmurs  are  present,  their  time  relationships  in  the  cardiac  cycle 
are  most  clearly  seen. 

Einthoven  has  further  found  the  presence  of  a  third  heart  sound,  which  is 
inaudible  to  the  unaided  ear,  although  it  was  first  described  by  Dr  A.  G.  Gibson 
of  Oxford,  in  a  patient  in  whom  it  was  very  pronounced,  by  means  of  ordinary 
auscultation.  It  seems,  however,  to  be  present  in  all  human  hearts  in  varying 
degrees  of  intensity  when  the  cardiophonogram  is  examined.  It  occurs  during 
diastole,  and  follows  the  second  sound  after  a  short  pause.  It  is  not  due  to  a 
reduplication  of  the  second  sound,  nor  is  it  a  presystolic  murmur  such  as  can  be 
heard  in  man  when  there  is  obstruction  at  the  auriculo-ventricular  orifices. 
Einthoven  adduces  evidence  against  both  these  views,  and  believes  it  is  produced 
at  the  aortic  orifice ;  the  semilunar  valves  and  the  neighbouring  portion  of  the 
aortic  wall  being  thrown  for  a  second  time  and  for  a  short  period  into  vibration 
by  the  changes  in  the  aortic  pressure  which  occur  during  diastole. 


CH.  XXI.] 


WORK  OF  THE  HEART 


247 


Frequency  of  the  Heart's  Action. 

The  heart  of  a  healthy  adult  man  contracts  about  72  times  in  a 
minute;  but  many  circumstances  cause  this  rate  to  vary  even  in 
health.  The  chief  are  age,  temperament,  sex,  food  and  drink, 
exercise,  time  of  day,  posture,  atmospheric  pressure,  temperature. 
Some  figures  in  reference  to  the  influence  of  age  are  appended. 

The  frequency  of  the  heart's  action  gradually  diminishes  from  the 
commencement  to  near  the  end  of  life,  thus : — 


Before  birth  the  average  number 

of  pulsations  per  minute  is  .  150 
Just  after  birth  .  .  from  140  to  130 
During  the  first  year  .  ,,  130  to  115 
During  the  second  year  ,,  115  to  100 


About  the  seventh  year  .    from  90  to  85 
About      the      fourteenth 

year  .  .  .  .  ,,  85  to  80 
In  adult  age  .  .  .  ,,  80  to  70 
In  old  age 70  to  60 


In  health  there  is  a  uniform  relation  between  the  frequency  of 
the  heart  -beats  and  of  the  respirations;  the  proportion  being  1 
respiration  to  3  or  4  beats.  The  same  relation  is  generally  main- 
tained in  cases  in  which  the  action  of  the  heart  is  naturally 
accelerated,  as  after  food  or  exercise;  but  in  disease  this  relation 
may  cease. 

Work  of  the  Heart. 

Waller  compares  the  work  performed  by  the  heart  in  a  day  to 
that  done  by  an  able-bodied  labourer  working  hard  for  two  hours. 
The  heart's  work  consists  in  discharging  blood  against  pressure,  and 
in  imparting  velocity  to  it.  It  is  therefore  necessary  to  know  how 
much  blood  is  expelled  from  the  heart  at  each  beat,  the  time 
occupied  in  such  expulsion,  the  velocity  with  which  the  blood  is 
expelled,  and  the  pressure  against  which  the  heart  has  to  act. 
Without  going  into  the  somewhat  elaborate  calculations  obtained 
from  these  and  other  data,  it  will  be  sufficient  to  say  that  about 
TV  of  the  total  energy  of  the  heart  is  used  in  imparting  velocity  to 
the  blood,  but  when  the  blood  reaches  the  aorta  the  velocity  is  checked, 
and  that  the  kinetic  energy  of  the  blood  in  the  aorta  is  only  about 
-g-Jrj-  of  the  total  energy  imparted  to  the  blood  by  the  heart. 


The  Output  of  the  Heart.  —  Direct  measurements  of  the  heart's  output  have 
been  made  by  Stolnikow  and  Tigerstedt.  The  former  cut  off  the  whole  of  the 
systemic  circulation  in  the  dog,  and  then  measured  the  amount  of  blood  passing 
through  the  simplified  circulation,  which  consisted  only  of  the  pulmonary  and 
coronary  vessels  by  means  of  a  cylinder  interposed  on  the  course  of  the  vessels, 
(see  fig.  228).  Tigerstedt  made  his  observations  by  means  of  a  Stromuhr  (see  next 
chapter)  inserted  into  the  aorta.  Severe  operative  measures  of  this  kind,  however, 
interfere  with  the  circulation  a  good  deal. 

G.  N.  Stewart  has  introduced  an  ingenious  method,  the  principle  of  which  is 
the  following  :  —  A  solution  of  an  innocuous  substance,  which  can  be  easily  recog- 
nised and  estimated,  is  allowed  to  flow  for  a  definite  time  and  at  a  uniform  rate  into 
the  heart  ;  the  substance  selected  was  sodium  chloride.  This  mingles  with  the 


248 


PHYSIOLOGY  OF  THE  HEART 


[CH.  XXI. 


blood  and  passes  into  the  circulation.  At  a  convenient  point  of  the  vascular 
system,  a  sample  of  blood  is  drawn  off  just  before  the  injection,  and  an  equal 
amount  during  the  passage  of  the  salt ;  the  quantity  of  the  sodium  chloride 
solution  which  must  be  added  to  the  first  sample  in  order  that  it  may  contain 
as  much  as  the  second  sample  is  determined.  This  determination  gives  the 
extent  to  which  the  salt  solution  has  been  mixed  with  the  blood  in  the  heart, 

and  knowing  the  quantity  of  the  solu- 
tion which  has  run  into  the  heart,  the 
output  in  a  given  time  can  be  calculated. 
All  these  experiments  have  been  on 
animals.  The  results  obtained  neces- 
sarily vary  with  the  size  of  the  animal 
used,  and  with  the  rate  at  which  the 
heart  is  beating.  If  the  same  relation- 
ship holds  for  man  as  for  animals, 
Stewart  calculates  that  in  a  man  weigh- 
ing 70  kilos  the  output  of  each  ventricle 
per  second  is  less  than  0  '002  of  the  body 
weight,  i.e.,  about  105  grammes  of 
blood  per  second,  or  87  grammes  (about 
80  c.c.)  per  heart-beat  with  a  pulse  rate 
of  72. 

An  instrument  called  the  cardi- 
ometer  was  invented  by  Roy  for  regis- 
tering the  output  of  the  heart.  His 
instrument  was  made  of  metal,  and  oil 
was  used  as  the  transmitting  medium 
in  its  interior.  A  simple  modification 
of  this  applicable  to  the  heart  of  a  small 
mammal  like  a  cat  has  been  devised  by 
Barnard.  It  consists  of  an  india-rubber 
tennis  ball  with  a  circular  orifice  cut  in 
one  side  of  it  large  enough  to  admit  the 
heart ;  a  glass  tube  is  securely  fixed  into 
a  small  opening  on  the  opposite  side 
of  the  ball.  The  animal  is  anaesthetised, 
and  its  thorax  opened.  The  animal  is 
kept  alive  by  artificial  respiration. 
The  pericardium  is  then  opened  by  a 
crucial  incision,  the  heart  is  slipped  into 
the  ball ;  the  pericardium  overlaps  the 
outside  of  the  ball,  and  the  apparatus 
is  rendered  air-tight  by  smearing  the 
edges  of  the  hole  with  vaseline.  The 
four  corners  of  the  pericardium  are  then 
tightly  tied  by  ligatures  round  the  glass 
tube  just  mentioned.  This  tube  is  con- 
nected by  a  stout  india-rubber  tube  to 
a  Marey's  tambour  or  a  piston-recorder, 
the  writing-point  of  which  is  applied  to 
a  moving  blackened  cylinder.  When 


FIG.  228.— Stolnikow's  apparatus.  A  and  B  are 
two  cylinders  fitted  with  floats  provided  with 
writing-points  at  their  upper  ends.  The  tube 
from  the  lower  end  of  each  bifurcates  into 
two,  a  and  v  from  A ;  a!  and  v'  from  B.  a  and 
a'  are  united  together  and  enter  the  right 
carotid  artery ;  v  and  v'  unite  and  are  inserted 
into  the  superior  vena  cava.  The  remaining 
branches  of  the  aorta  and  the  inferior  vena 
cava  are  tied.  B  is  first  filled  with  defibrin- 
ated  blood,  which  passes  down  v'  into  the 
right  auricle,  thence  to  the  right  ventricle, 
lungs  (where  it  is  oxygenated),  and  then 
enters  the  left  side  of  the  heart ;  the  left 
ventricle  expels  it  by  the  tube  a  into  A,  so 
that  the  float  in  A  rises  while  that  in  B  falls. 
As  soon  as  B  is  empty  the  tubes  v  and  a' 
which  were  previously  clamped  are  released, 
and  v'  and  a  are  clamped  instead.  The  left 
ventricle  now  expels  its  blood  by  the  tube  a' 
into  the  cylinder  B ;  simultaneously  A  empties 
itself  through  v  into  the  right  side  of  the 
heart.  Zigzag  lines  are  thus  traced  by  the 
writing-points  on  the  top  of  the  floats,  and 
their  frequency  enables  one  to  estimate  the 
output  of  the  left  ventricle  in  a  given  time. 
(After  Starling.) 


the  heart  contracts,  air  will  be  with- 
drawn from  the  tambour  to  the  cardi- 
ometer ;  when  the  heart  expands,  the  air  will  move  in  the  reverse  direction. 
.These  movements  are  written  by  the  end  of  the  lever  of  the  tambour,  and  varia- 
tions in  the  excursions  of  this  lever  correspond  with  variations  in  the  amount  of 
blood  expelled  from  or  drawn  into  the  heart  with  systole  and  diastole  respec- 
tively. By  calibrating  the  instrument  the  actual  volume  of  the  blood  expelled  can 
be  ascertained. 


CH.  XXL]  INNERVATION  OF  THE  HEART  249 

Innervation  of  the  Heart. 

The  nerves  of  the  heart,  which  under  normal  circumstances 
control  its  movements,  are : — 

1.  Cardiac  branches  of  the  vagus  (inhibitory  fibres). 

2.  Cardiac  branches  of  the  sympathetic  (augmentor  and  acceler- 
ator fibres). 

These  pass  to  the  heart  and  terminate  in  certain  collections  of 
ganglion  cells  in  its  wall  (terminal  ganglia) ;  from  these  cells  post- 
ganglionic  fibres  are  distributed  among  the  muscular  fibres.  In 
addition  to  these  nerves,  which  are  efferent,  we  have  to  mention : — 

The  sensory  or  afferent  nerves  of  the  heart,  the  best  known  of 
which  is  called  the  depressor  nerve.  This  nerve,  starting  from  the 
cardiac  tissue,  joins  the  vagus  trunk;  it  passes  to  the  bulb,  especially 
to  the  vaso-motor  centre.  We  shall  therefore  postpone  its  study 
until  we  are  considering  the  vaso-motor  nerves. 

The  Vagus. — The  ninth,  tenth,  and  eleventh  cranial  nerves  arise 
close  together  from  the  grey  matter  in  the  floor  of  the  fourth  ventricle, 
and  leave  the  bulb  by  a  number  of  rootlets.  These  rootlets  are 
divided  by  Grossmann  into  three  groups,  a,  &,  and  c ;  there  is  a  good 
deal  of  blending  of  the  rootlets  before  they  ultimately  emerge  from 
the  skull,  but  the  a  (the  uppermost)  group  corresponds  fairly 
well  with  the  fibres  of  the  glossopharyngeal,  b  with  those  of 
the  vagus,  and  c  (the  lowermost)  with  those  of  the  spinal  acces- 
sory. The  rootlets  of  the  tenth  nerve  pass  through  two  ganglia 
called  respectively  the  jugular  ganglion,  and  the  ganglion  trunci 
vagi.  The  fibres  of  the  spinal  accessory  nerve  which  join  the 
vagus  are  chiefly  motor,  especially  to  the  larynx,  but  some  go  to  the 
heart.  The  vagus  gives  off  branches  to  many  organs,  pharynx,  larynx, 
heart,  lungs,  oesophagus,  and  various  abdominal  organs.  We  have, 
however,  in  this  place  only  to  deal  with  its  cardiac  fibres.  It  has 
been  known  since  the  experiments  of  the  Brothers  Weber  in  1845 
that  stimulation  of  one  or  both  vagi  produces  slowing  or  stoppage  of 
the  beats  of  the  heart.  It  has  since  been  shown  that  in  all  vertebrate 
animals,  this  is  the  normal  result  of  vagus  stimulation ;  the  pheno- 
menon is  called  inhibition,  and  the  nerve-fibres  cardio-irihibitory. 
Section  of  one  vagus  produces  slight  acceleration  of  the  heart ;  this 
result  is  better  marked  when  both  vagi  are  divided.  This  shows  that 
the  restraining  influence  of  the  vagus  is  being  continuously  exercised ; 
it  is,  however,  found  that  the  amount  of  vagus  control  varies  a 
good  deal  in  different  animals.  The  most  potent  artificial  stimulus 
which  can  be  applied  to  the  vagus  nerve  to  produce  inhibition  of  the 
heart  is  a  rapidly  interrupted  induction  current ;  severe  mechanical 
stimuli  have  a  slight  effect,  but  chemical  and  thermal  stimuli  are 
ineffective. 


250  PHYSIOLOGY  OF   THE   HEART  [CH.  XXI. 

A  certain  amount  of  confusion  has  arisen  as  to  the  effect  of  vagus 
stimulation,  because  so  many  experiments  have  been  made  on  the 
frog.  In  this  animal  the  sympathetic  fibres  join  the  vagus  after  it 
leaves  the  skull,  and  so  what  is  usually  called  the  vagus  in  this 
animal  should  more  properly  be  termed  the  vago-sympathetic.  It  will 
readily  be  understood  that  by  stimulating  a  mixed  nerve,  one  obtains 


FIG.  229. — Tracing  showing  the  actions  of  the  vagus  on  the  heart.  Aur.}  auricular  ;  Vent.,  ventricular 
tracing.  The  part  between  the  perpendicular  lines  indicates  the  period  of  vagus  stimulation.  C.8 
indicates  that  the  secondary  coil  was  8  c.m.  from  the  primary.  The  part  of  the  tracing  to  the  left 
shows  the  regular  contractions  of  moderate  height  before  stimulation.  During  stimulation,  and 
for  some  time  after,  the  beats  of  auricle  and  ventricle  are  arrested.  After  they  commence  again 
they  are  small  at  first,  but  soon  acquire  a  much  greater  amplitude  than  before  the  application  of 
the  stimulus.  (From  Brunton,  after  Gaskell.) 

an  intermixture  of  effects.  If,  however,  one  stimulates  the  intra- 
cranial  vagus  before  the  sympathetic  blends  with  it,  a  pure  inhibitory 
effect  is  obtained.  Figs.  229  and  230  show  the  common  effect  of 
stimulating  the  mixed  trunk ;  the  inhibitory  effect  is  usually  mani- 
fested first,  and  this  is  followed  by  the  augmentor  effect  due  to 


Fro.  230.— Tracing  showing  diminished  amplitude  and  slowing  of  the  pulsations  of  the  auricle  and 
ventricle  without  complete  stoppage  during  stimulation  of  the  vagus.  (From  Brunton,  after 
Gaskell.) 

sympathetic  action.  But  it  is  by  no  means  infrequent  to  obtain  the 
phenomena  in  the  reverse  order.  It  is  often  stated  that  the  right 
nerve  contains  more  inhibitory  fibres  than  the  left,  but  this  is  by  no 
means  a  constant  rule.  One  can  always  obtain  good  inhibition  if  the 
stimulus  is  applied  to  the  wall  of  the  sinus;  here  one  stimulates 
the  post-ganglionic  fibres  which  originate  from  the  nerve-cells  in 
the  sinus  ganglion  around  which  the  vagi  terminate. 


CH.  XXI.] 


CAEDIAC   SYMPATHETIC   NERVES 


251 


The  effect  of  the  stimulus  is  not  immediately  seen ;  one  or  more 
beats  may  occur  before  stoppage  of  the  heart  takes  place,  and  slight 
stimulation  may  produce  only  slowing  and  not  complete  stoppage  of 
the  heart  (fig.  230).  The  stoppage  may  be  due  either  to  prolongation 
of  the  diastole,  as  is  usually  the  case,  or  to  diminution  of  the  systole. 
Vagus  stimulation  lessens  the  conductivity  of  the  cardiac  tissue,  but 
it  does  not  abolish  the  irritability  of  the  heart-muscle,  since  direct 
mechanical  stimulation  may  bring  out  a  beat  during  the  standstill 
caused  by  vagus  stimulation.  The  inhibition  of  the  beats  varies  in 
duration,  but  if  the  stimulation  is  a  prolonged  one,  the  beats  reappear 
before  the  current  is  shut  off.  This  is  known  as  "  vagus  escape,"  and 
is  probably  due  to  fatigue  of  the  vagal  endings. 

The  Sympathetic. — The  influence  of  the  sympathetic  is  the 
reverse  of  that  of  the  vagus.  Stimulation  of  the  sympathetic 
produces  acceleration  of  the 
heart-beats,  and  as  a  rule,  sec- 
tion of  the  nerve  produces 
slowing.  Hence  the  nerve  is 
also  in  constant  action  like 
the  vagus.  The  acceleration 
produced  by  stimulation  of  the 
sympathetic  fibres  is  accom- 
panied by  increased  force,  and 
so  the  action  of  the  nerve  is 
also  termed  augmentor.  It  is 
probable  that  the  augmentor 
fibres  are  distinct  from  the 
accelerator  fibres,  because  in 
mammals  one  or  two  of  the 
small  nerves  leaving  the  stel- 
late ganglion  on  stimulation 
produce  augmentation  without 
acceleration. 

The  fibres  of  the  sympa- 
thetic system  which  influence 
the  heart-beat  in  the  frog, 
leave  the  spinal  cord  by  the 
anterior  root  of  the  third 


Post,  root 


spinal  nerve,  and  pass  by  the 

ran  ins    communicans    to    the 

third     sympathetic    ganglion, 

then  to  the  second  sympathetic  ganglion,  then  by  the  annulus  of 

Vieussens  (round  the  subclavian  artery)  to  the  first   sympathetic 

ganglion,  and  finally  in  the  main  trunk  of  the  sympathetic,  to  near 

the  exit  of  the  vagus  from  the  cranium,  where  it  joins  that  nerve 


FIG.  231. — Heart  nerves  of  frog.    (Diagrammatic.) 


252 


PHYSIOLOGY   OF   THE   HEART 


[CH.  XXI. 


JugularGanglion 


Ganglion 
trunci 
Vagi 


and  runs  down  to  the  heart  within  its  sheath,  forming  the  joint  vago- 
sympathetic  trunk.  These  fibres  are  indicated  by  the  dark  line  in 
fig.  231.  The  fibres  of  the  sympathetic  seen  running  up  into  the 
skull  are  for  the  supply  of  blood-vessels  there.  It  should  be  noted 
that  the  frog  has  no  spinal  accessory  nerve. 

In  the  mammal   the  sympathetic   fibres   leave  the  cord  by  the 

second  and  third  dorsal 
nerves,  and  possibly  by  an- 
terior roots  of  two  or  more 
lower  nerves ;  they  pass  by 
the  rami  communicantes  to 
the  ganglion  stellatum,  or 
first  thoracic  ganglion,  and 
thence  by  the  annulus  of 
Vieussens  to  the  inferior 
cervical  ganglion  of  the  sym- 
pathetic ;  fibres  from  the  an- 
nulus, or  from  the  inferior 
cervical  ganglion,  proceed  to 
the  heart  (see  fig.  232). 

In  man,  the  cardiac 
branches  of  the  sympa- 
thetic travel  to  the  heart 
from  the  annulus  of  Vieus- 
sens and  cervical  sympa- 
thetic in  superior,  middle, 
and  lower  bundles  of  fibres. 
These  pass  into  the  cardiac 
plexus,  and  surrounding  the 
coronary  vessels  ultimately 
reach  the  heart. 


Inferior  Cervical 
Ganglion 

Subclauian 
A rtery 

Annulus 


Ganglion  Stellatum 


Ant.  root 

nd.Thoracic 

Nerue 

~Post.root 


Third 
Thoracic 
Ganglion 


PIG.  232.— Heart  nerves  of  mammal.    (Diagrammatic.) 


By  stimulating  each  rootlet 
in  his  three  groups,  Grossmann 
found  the  cardio-inhibitory  fibres 
in  the  lower  two  or  three  rootlets 
of  group  b  and  the  upper  rootlet 
of  group  c.  There  are  probably 
differences  in  different  animals. 
In  the  cat  and  dog  Cadman  finds 
that  the  rootlets  in  the  a  group 

are  respiratory  and  afferent  inhibitory,  and  that  all  the  efferent  inhibitory  fibres  are 
in  group  c. 

The  inhibitory  fibres  are  medullated,  and  only  measure  2  p  to  3  p  in  diameter  ; 
they  pass  to  the  heart  and  have  their  cell-stations  in  the  ganglia  of  that  organ. 
Some  of  the  sympathetic  fibres,  on  the  other  hand,  reach  the  heart  as  non- 
medullated  fibres ;  having  their  cell-stations  in  the  sympathetic  (inferior  cervical 
and  first  thoracic)  ganglia ;  but  the  majority  do  not  reach  their  cell-stations  until 
they  reach  terminal  ganglia  in  the  heart  wall.  The  augmentor  and  accelerator 
centres  in  the  central  nervous  system  have  not  yet  been  accurately  localised. 


CH.  XXI.]  CARDIAC   SYMPATHETIC   NERVES  253 

Influence  of  Drugs. — The  question  of  the  action  of  drugs  on  the 
heart  forms  a  large  branch  of  pharmacology.  We  shall  be  content 
here  with  mentioning  two  only,  as  they  are  largely  used  for  experi- 
mental purposes  by  physiologists.  Atropine  produces  consider- 
able augmentation  of  the  heart-beats  by  paralysing  the  inhibitory 
mechanism.  Muscarine  (obtained  from  poisonous  fungi)  produces 
marked  slowing,  and  in  larger  doses  temporary  stoppage  of  the 
heart.  Its  effect  is  a  prolonged  inhibition,  and  can  be  removed  by 
the  action  of  atropine.  The  action  of  atropine  cannot,  however,  be 
easily  antagonised  by  muscarine ;  a  large  dose  is  necessary.  That  these 
drugs  act  on  the  nerves,  and  not  the  muscular  substance  of  the 
heart,  is  shown  by  the  fact  that  in  the  hearts  of  early  embryos,  so 
early  that  no  nerves  have  yet  grown  to  the  heart,  these  drugs  have 
little  or  no  effect.  (Pickering.) 

Reflex  Inhibition. — Thus  there  is  no  doubt  that  the  vagi  nerves 
are  simply  the  media  of  an  inhibitory  or  restraining  influence  over 
the  action  of  the  heart,  which  is  conveyed  through  them  from  the 
centre  in  the  medulla  oblongata,  which  is  always  in  operation.  The 
restraining  influence  of  the  centre  in  the  medulla  may  be  reflexly 
increased  by  stimulation  of  many  afferent  nerves,  particularly  those 
from  the  nasal  mucous  membrane,  the  larynx,  and  the  lungs.  A 
blow  on  the  abdomen  causes  inhibition  and  fainting ;  a  blow  on  the 
larynx,  even  a  moderate  one,  will  kill.  There  is  no  comparison 
between  the  ease  with  which  stimulation  of  the  laryngeal  or  pul- 
monary fibres  produces  inhibition,  as  compared  to  the  difficulty  of 
obtaining  inhibition  from  the  alimentary  tract.  Tobacco  smoke  in 
some  people  and  animals,  by  acting  on  the  terminations  of  the 
vagi  or  their  branches  in  the  respiratory  system,  may  also  produce 
reflex  inhibition  of  the  heart.  Some  very  remarkable  facts  concern- 
ing the  readiness  by  which  reflex  inhibition  of  the  fish's  heart  may 
be  produced  were  made  out  by  M 'William ;  any  irritation  of  the  tail, 
gills,  mucous  membrane  of  mouth  and  pharynx,  or  of  the  parietal 
peritoneum,  causes  the  heart  to  stop  beating. 

In  connection  with  the  subject  of  reflex  inhibition,  it  may  be 
mentioned  in  conclusion  that  though  we  have  no  voluntary  control 
over  the  heart's  movements,  yet  cerebral  excitement  will  produce  an 
effect  on  the  rate  of  the  heart,  as  in  certain  emotional  conditions. 

Action  of  Chloroform  on  the  Cardiac  Mechanism. — The  mammalian 
heart  is  more  difficult  to  stop  by  stimulation  of  the  vagus  than  the 
frog's  heart ;  commonly  it  is  only  slowed,  and  the  amplitude  of  the 
beat  reduced,  yet  it  is  most  important  for  the  student  of  medicine 
to  recollect  that  vagus  inhibition  may  have  far-reaching  results. 
One  of  the  most  familiar  causes  of  heart  stoppage  in  surgical  practice 
is  that  produced  by  chloroform;  chloroform  acts  directly  on  the 
cardiac  tissue  when  it  is  administered  incautiously,  or  in  too  large 


254 


PHYSIOLOGY  OF  THE   HEART 


[CH.  XXI. 


doses  over  long  periods  of  time ;  the  term  inhibition  is  not  applicable 
in  this  case,  and  the  effects  of  the  poisonous  action  of  chloroform  on 
the  heart  itself  can  be  avoided  by  keeping  the  proportion  of  chloro- 
form in  the  inspired  air  at  2  per  cent,  or  less.  But  in  other  cases 
which  are  seen  both  in  animals  and  human  beings  who  may  be 
peculiarly  susceptible  to  the  influence  of  chloroform,  heart  stoppage 
occurs  during  the  onset  of  anaesthesia  long  before  the  percentage  of 
chloroform  in  the  blood  has  reached  a  value  which  is  toxic  to  the 
heart.  Some  have  considered  that  death  during  the  induction  of 
chloroform  anaesthesia  is  due  to  the  vapour  irritating  the  vagal 
terminations  in  the  lung,  and  so  leading  to  reflex  inhibition  of  the 
heart.  Embley's  experiments,  however,  lead  to  the  conclusion  that 
the  chloroform  acts  on  the  vagus  centre  in  the  medulla  oblongata. 
In  animals,  cutting  the  vagi  immediately  sets  the  heart  going  again. 
In  man  this  operation  cannot  be  performed,  and  it  is  therefore  a  wise 
precaution,  whenever  it  is  necessary  to  administer  chloroform,  to 
give  beforehand  a  small  dose  of  atropine  under  the  skin  so  as  to 
temporarily  paralyse  the  vagus  endings  in  the  heart. 

Gaseous  Exchanges  in  the  Heart. — The  using  up  of  oxygen  by  the 
living  heart  was  well  illustrated  by  an  old  experiment  of  Yeo's.  He 
passed  a  weak  solution  of  oxyhseinoglobin  through  an  excised  beat- 
ing frog's  heart,  and  found  that  after  it  had  passed  through  the  heart, 
the  solution  became  less  oxygenated  and  venous  in  colour. 

This  is  still  better  shown  by  the  following  numbers,  obtained 
by  Barcrof  t  and  Dixon  by  estimating  the  gases  in  the  blood  entering 
and  leaving  the  coronary  vessels  of  a  cat.  It  will  be  seen  that  the 
metabolism  in  the  heart  tissue  is  reduced  during  inhibition;  this  is 
followed  by  increased  metabolism  during  the  subsequent  period, 
which  corresponds  with  the  increase  of  visible  activity  which  then 
occurs,  and  which  is  seen  in  the  tracings  given  in  figs.  229  and  230. 


Oxygen  used  up  per  minute 
Carbonic  acid  given  out  per  minute 

Normal  Heart. 

During  Vagus 
Inhibition. 

After  Vagus 
Inhibition. 

0-21  C.C. 
0-45  C.C. 

0-13  c.c. 
0'07  c.c. 

0-34  C.C. 
0-22  c.c. 

Rhythm,  Conduction,  etc.,  in  Cardiac  Muscle. 

In  one  time,  the  rhythm  which  cardiac  muscle  exhibits  was 
supposed  to  be  due  to  the  action  upon  it  of  the  nerves  which  are 
present.  We  now  know  that  the  property  of  rhythmical  peristalsis 
resides  in  the  muscular  tissue  itself,  though  normally  during  life  it  is 
controlled  and  regulated  by  the  nerves  that  supply  it.  This  conclusion 
may  be  expressed  by  saying  that  cardiac  rhythm  is  myoyenic,  not 


CH.  XXI.]  CARDIAC    RHYTHM   AND    CONDUCTION  255 

neurogenic.  There  are  still  a  few  physiologists  who  maintain  the 
older  neurogenic  theory,  but  these  are  mainly  those  whose  chief  work 
has  been  performed  on  the  hearts  of  invertebrate  animals,  and  it  is 
quite  possible  that  the  mechanism  there  is  a  different  one.  But  so 
far  as  the  vertebrate  heart  is  concerned,  the  myogenic  theory  is  now 
held,  because  (1)  the  foetal  heart  manifests  rhythm  long  before  any 
nerves  reach  it ;  (2)  the  apex  of  the  ventricle  of  such  animals  as  frogs 
and  tortoises  can  be  made  to  beat  rhythmically  by  perfusing  it 
with  suitable  fluids  at  high  pressure ;  and  this  part  of  the  heart  has 
few  nerves  and  no  ganglion  cells ;  and  (3)  the  rate  of  conduction  of 
the  peristaltic  wave  is  slow,  and  corresponds  to  the  rate  of  muscular 
rather  than  of  nervous  conduction. 

The  older  observers,  who  first  made  the  striking  observation  that 
a  heart  will  continue  to  beat  after  its  removal  from  the  body  for  a 
considerable  period,  and  who  at  the  same  time  were  imbued  with 
the  neurogenic  theory,  naturally  placed  the  seat  of  rhythm  in  the 
intracardiac  ganglia.  They  were  not  at  the  time  aware  of  the  general 
arrangements  of  autonomic  nerves,  and  therefore  did  not  recognise 
that  the  ganglia  were  terminal  cell-stations  on  the  course  of  the 
nerves  which  reach  the  heart  via  vagus  and  sympathetic. 

The  intracardiac  nerves  have  been  chiefly  studied  in  the  frog ;  in 
this  animal  the  two  vago-sympathetic  nerves  terminate  in  various 
groups  of  ganglion-cells ;  of  these  the  most  important  are  Remalts 
ganglion,  situated  at  the  junction  of  the  sinus  with  the  right  auricle; 
and  Bidder's  ganglion,  at  the  junction  of  the  auricles  and  ventricle. 
A  third  collection  of  ganglion  cells  (von  Bezold's  ganglion)  is  situated 
in  the  interauricular  septum.  From  the  ganglion  -  cells,  post- 
ganglionic  fibres  spread  out  over  the  walls  of  the  sinus,  auricles,  and 
upper  part  of  the  ventricle.  Kemak's  ganglion  used  to  be  called  the 
local  inhibitory  centre  of  the  heart ;  it  is  really  the  chief  cell-station 
of  the  inhibitory  fibres,  and  stimulation  of  the  heart  at  the  sino- 
auricular  junction  is  the  most  certain  way  of  obtaining  stoppage  of 
the  heart.  Bidder's  ganglion  was  called  the  local  accelerator  centre 
for  a  corresponding  reason. 

The  intracardiac  ganglia  have  been  examined  in  a  few  other  cold- 
blooded animals  (for  instance  the  tortoise),  but  any  precise  knowledge 
of  their  arrangement  and  position  in  the  mammalian  and  human 
heart  is  unfortunately  lacking. 

Conduction  in  the  Heart. — As  already  stated,  the  slow  rate  of 
propagation  of  the  wave  points  to  the  link  being  muscular  rather 
than  nervous,  and  histology  lends  support  to  this  view,  the  muscular 
fibres  being  connected  to  each  other  by  intercellular  bridges  of  proto- 
plasm (see  p.  71).  An  experimental  proof  of  the  same  view  is  the 
following:  if  a  strip  of  the  heart  wall  is  taken  and  a  number  of 
cuts  going  nearly  completely  across  it,  be  made  first  from  one  side, 


256  PHYSIOLOGY   OF   THE   HEART  [CH.  XXI. 

then  from  the  other,  all  the  nerves  must  be  cut  through  at  least  once, 
and  the  only  remaining  tissue  not  severed  is  muscular,  yet  the  strip 
still  continues  to  beat ;  in  other  words,  the  propagation  is  myodromic. 
The  passage  of  the  wave  from  one  chamber  to  another  is  also  myo- 
dromic. The  slow  rate  of  propagation  indicates  that  this  is  so,  and 
the  view  has  been  fully  proved  by  the  discovery  of  muscular  strands, 
passing  across  from  one  chamber  to  the  next. 

It  appears  that  under  normal  conditions  the  wave  of  contraction 
in  the  heart  starts  at  the  sinus,  and  travels  over  the  auricles  to  the 
ventricle ;  the  irritability  of  the  muscle  and  the  power  of  rhythmic 
contractility  is  greatest  in  the  sinus,  less  in  the  auricles,  and  still  less 
in  the  ventricles.  Under  ordinary  conditions  the  apical  portion  of 
the  ventricles  exhibits  very  slight  power  of  spontaneous  contraction. 
The  importance  of  the  sinus  as  the  starting-point  of  the  peristalsis 
can  be  shown  by  warming  it.  If  a  frog's  heart  is  warmed  by  bathing 
it  in  warm  salt  solution  at  about  body  temperature,  it  beats  faster ; 
this  is  due  to  the  sinus  starting  a  larger  number  of  peristaltic  waves ; 
that  this  is  the  case  may  be  demonstrated  by  warming  localised  portions 
of  the  heart  by  a  small  galvano-cautery ;  if  the  sinus  is  warmed  the 
heart  beats  faster,  but  if  the  auricles  or  ventricles  are  warmed  there 
is  no  alteration  in  the  heart's  rate.  The  sinus  in  the  frog's  heart, 
and  that  portion  of  the  right  auricle  in  the  mammal's  heart  which 
corresponds  to  the  sinus,  is  always  the  last  portion  of  the  heart  to 
cease  beating  on  death,  or  after,  removal  from  the  body  (ultima 
moriens,  Harvey).  This  is  an  additional  proof  of  the  superior  rhyth- 
mical power  which  it  possesses.  The  foetal  remnant  of  the  sinus 
in  the  mammal's  heart  has  been  called  the  sino-auricular  ncde  (Keith 
and  Flack),  and  this  has  been  believed  to  act  as  the  "  pace-maker  " 
of  the  heart.  But  after  its  removal  other  parts  in  the  same  region 
which  contain  no  Purkinje's  fibres  have  been  found  quite  capable 
of  maintaining  the  ordinary  cardiac  rhythm.  The  sino-auricular 
node  cannot  therefore  be  the  specific  or  exclusive  pace-maker,  and 
some  observers  regard  the  final  part  of  the  large  veins  outside  the 
heart  altogether  as  more  important  from  this  point  of  view. 

It  is  supposed  that  the  wave  starting  at  the  sinus  is  more  or  less 
blocked  by  a  ring  of  lower  irritability  at  its  junction  with  the  auricle ; 
again,  the  wave  in  the  auricle  is  similarly  delayed  in  its  passage  over 
to  the  ventricle  by  a  ring  of  lesser  irritability,  and  thus  the  wave  of  con- 
traction is  delayed  at  its  entrance  into  both  auricular  and  ventricular 
tissue.  By  an  arrangement  of  ligatures,  or,  better,  of  clamps,  one  part 
of  the  heart  may  be  isolated  from  the  other  portions,  and  the  contrac- 
tion when  aroused  by  an  induction  shock  may  be  made  to  stop  in  the 
portion  of  the  heart  muscle  in  which  it  begins.  It  is  not  unlikely 
that  the  contraction  of  one  portion  of  the  heart  acts  as  a  stimulus 
to  the  next  portion,  and  that  clamps  and  ligatures  prevent  or  "  block  " 


CH.  XXI.]  HEART-BLOCK  257 

this  normal  propagation  of  stimuli.  It  must  not,  however,  be  thought 
that  the  wave  of  contraction  is  incapable  of  passing  over  the  heart  in 
any  other  direction  than  from  the  sinus  onwards;  for  it  has  been 
shown  that  by  the  application  of  appropriate  stimuli  at  appropriate 
instants,  the  natural  sequence  of  beats  may  be  reversed,  and  the  con- 
traction starting  at  the  arterial  part  of  the  ventricle  may  pass  to  the 
auricles  and  then  to  the  sinus.  If  clamps  or  ligatures  are  not  applied 
sufficiently  tightly  one  often  sees  partial  blocking ;  a  few  waves  get 
through  but  not  all;  or  if  the  ventricular  wall  is  left  connected 
with  other  parts  of  the  heart  by  only  a  small  portion  of  undivided 
muscular  tissue,  the  effect  is  much  the  same,  the  wave  is  only  able 
to  pass  the  block  every  second  or  third  beat. 

Heart-Block. — The  phenomena  of  blocking  just  described  were 
made  out  by  Gaskell  many  years  ago  in  his  study  of  the  hearts  of 
cold-blooded  animals.  But  the  same  sort  of  thing  occurs  also  in  the 
mammalian  heart.  The  starting-point  in  our  knowledge  of  this 
branch  of  the  subject  was  the  discovery  by  Stanley  Kent  of  bands 
of  muscular  tissue  passing  across  from  auricles  to  ventricles,  and 
the  principal  one  was  subsequently  and  independently  re-discovered 
by  His,  and  is  known  as  Kent's  bridge  or  the  Bundle  of  His,  or 
better  as  the  auricula-ventricular  bundle.  It  arises  in  close  con- 
nection with  the  fibres  of  the  interauricular  septum,  and  with  the 
tissue  of  the  sino-auricular  node  at  the  junction  of  the  superior 
vena  cava  and  right  auricle.  It  comes  also  into  relationship  with 
another  similar  mass  or  foetal  residue  known  as  the  auriculo- 
ventricular  node  which  lies  at  the  base  of  the  auricular  septum  on 
the  right  side  below  the  coronary  sinus.  From  here  the  bundle 
runs  along  the  top  of  the  intraventricular  septum  and  divides  into 
right  and  left  sub-divisions  which  run  down  to  their  respective 
ventricles  along  the  septum  which  separates  them,  and  into  the 
papillary  muscles  arising  from  the  septum.  From  the  papillary 
muscles  fine  strands  run  to  other  parts  of  the  ventricle  immediately 
under  the  endocardium,  and  finally  reach  the  apex.  All  these 
structures  are  made  of  the  peculiar  muscular  fibres  known  as 
Purkinje's  fibres  (see  p.  71).  There  is  no  doubt  that  this  is  the 
main  conducting  path  from  auricles  to  ventricles,  and  although  there 
are  nerve-fibres  mingled  with  the  muscular  fibres  of  Purkinje  there 
is  no  reason  for  modifying  the  view  already  expressed  that  con- 
duction is  myodromic. 

The  conclusion  that  the  auriculo- ventricular  bundle  is  the 
important  link  which  propagates  the  rhythmic  wave  has  been 
reached  first  by  experiments  on  animals,  and  secondly,  by  observa- 
tions in  disease  in  man.  In  animals,  cutting  through  the  bundle 
abolishes  the  ordinary  sequence  of  cardiac  events.  The  auricles  go 
on  beating,  but  the  ventricles  stop  altogether,  and  later  when  they 

K 


258  PHYSIOLOGY  OF  THE  HEART  [CH.  XXL 

do  begin  to  beat  again,  the  ventricular  beat  is  much  less  frequent 
than  the  auricular,  and  bears  no  relationship  to  it.  This  lack  of 
correspondence  in  auricular  and  ventricular  rhythm  is  known  as 
arhythmia. 

When  the  bundle  is  destroyed  by  disease  in  man  (Stokes- Adams' 
disease)  there  is  a  similar  dissociation  between  the  auricular  and 
ventricular  rhythm,  the  ventricles  beating  slowly  and  the  auricles 
rapidly.  Sometimes  the  "heart-block"  is  incomplete.  This  is  seen 
in  the  early  stages  of  the  disease ;  then  one  out  of  every  two  or 
three  auricular  waves  gets  over  to  the  ventricle,  just  as  in  Gaskell's 
experiments  on  the  frog's  heart  when  the  clamp  is  not  sufficiently  tight. 

These  recently  discovered  facts  throw  a  good  deal  of  light  on 
the  propagation  of  the  normal  heart  wave.  It  starts  in  the  sino- 
auricular  node,  and  spreads  thence  to  both  auricles ;  it  also  travels 
to  the  ventricles  by  the  auriculo- ventricular  bundle,  reaching  first 
the  papillary  muscles,  and  thence  the  rest  of  the  heart  until  it 
arrives  at  the  apex,  and  finally  returns  by  the  spiral  fibres  (see 
p.  212)  to  the  base  of  the  heart  in  the  region  of  the  origin  of  the 
pulmonary  artery,  which  is  the  representative  of  the  bulbus  aortse  of 
the  primitive  heart.  It  is  therefore  not  surprising  that  the  electro 
cardiogram  (p.  246)  is  complex.  The  wave  P  due  to  auricular 
activity  is  followed  by  a  pause  before  the  waves  which  accompany 
ventricular  systole  occur.  During  this  pause  it  is  supposed  that 
the  excitatory  wave  is  travelling  along  the  auriculo -ventricular 
bundle,  the  mass  of  which  is  too  small  to  affect  the  galvanometer. 
The  pause  which  intervenes  after  the  wave  E,  which  is  the  sign  of 
commencing  ventricular  activity,  is  supposed  to  be  due  to  a  state  of 
equipotentiality  when  the  great  mass  of  the  circular  muscles  of  the 
ventricle  are  contracting;  the  final  wave  T  indicates  the  arrival  of 
the  contraction  wave  at  the  base  by  the  spiral  fibres. 

The  Stannius  Experiment. — This  consists  in  applying  a  tight  ligature 
to  the  heart  between  the  sinus  and  the  right  auricle ;  the  sinus 
continues  to  beat,  but  the  rest  of  the  heart  is  quiescent.  The  quiescent 
parts  of  the  heart  may  be  made  to  contract  in  response  to  mechanical 
or  electrical  stimulation.  If  a  second  ligature  is  applied  to  the 
junction  of  the  auricles  with  the  ventricle,  the  ventricle  begins  to 
beat  again;  the  auricles  may  also  beat,  but  they  usually  do  not. 
According  to  Gaskell,  the  effect  of  the  first  ligature  is  simply  an 
example  of  blocking ;  it  is,  however,  difficult  to  wholly  accept  this 
view,  for  if  instead  of  applying  a  ligature  at  the  sino-auricular 
junction,  the  heart  wall  is  simply  cut  through  at  this  spot,  the 
auricles  and  ventricle  are  not  thereby  always  rendered  quiescent.  It 
appears  probable,  therefore,  that  there  is  some  truth  in  the  older 
view  that  the  ligature  acts  as  a  stimulus  irritating  the  vagal  termi- 
nations in  Eemak's  ganglion,  and  so  eliciting  a  condition  of  prolonged 


CH.  XXI.]  THE  STANNIUS  EXPERIMENT  259 

inhibition;  this,  however,  passes  off  after  a  variable  time,  and  the 
auricles  and  ventricle  once  more  beat  rhythmically.  It  is  impossible 
to  explain  the  effect  of  the  second  Stannius  ligature  except  on  the 
hypothesis  that  it  acts  as  a  stimulus,  and  there  is  no  a  priori  reason 
why  the  two  ligatures  should  act  in  opposite  ways. 

The  fact  that  the  Stannius  heart  is  quiescent  has  enabled 
physiologists  to  study  the  effects  of  stimuli  upon  heart  muscle.  A 
single  stimulus  produces  a  single  contraction,  which  has  a  long  latent 
period,  is  slow,  and  propagated  as  a  wave  over  the  heart  at  the  rate 
of  f  to  f  inch,  or  10 — 15  mm.  a  second.  A  second  stimulus  causes 
a  rather  larger  contraction,  a  third  one  larger  still,  and  so  on  for 
some  four  or  five  beats,  when  the  size  of  the  contraction  becomes 
constant.  This  staircase  phenomenon,  as  it  is  called,  is  also  seen  in 
voluntary  muscle,  but  it  is  more  marked  in  the  heart.  The  accom- 
panying tracing  (fig.  233)  shows  the  result  of  an  actual  experiment. 


FJ<;.  233. — Staircase  from  frog's  heart.  This  was  obtained  from  a  Stauuius  preparation;  au  induction 
shock  being  sent  into  it  with  every  revolution  of  the  cylinder  (rapid  rate).  The  contractions 
became  larger  with  every  beat.  To  be  read  from  right  to  left. 

There  are,  however,  more  marked  differences  than  this  between 
voluntary  and  heart  muscle.  The  first  of  these  is,  that  the  amount 
of  contraction  does  not  vary  with  the  strength  of  the  stimulation.  A 
stimulus  strong  enough  to  produce  a  contraction  at  all  brings  out  as 
big  a  beat  as  the  strongest.  The  second  is,  that  the  heart  muscle 
has  a  long  refractory  period ;  that  is  to  say,  after  the  application  of 
a  stimulus,  a  second  stimulus  will  not  cause  a  second  contraction 
until  after  the  lapse  of  a  certain  interval  called  the  refractory  period. 
The  refractory  period  lasts  as  long  as  the  contraction  period.  The 
third  difference  depends  on  the  second,  and  consists  in  the  fact  that 
the  heart-muscle  can  never  be  thrown  into  complete  tetanus  by  a  rapid 
series  of  stimulations ;  with  a  strong  current  there  is  a  partial  fusion 
of  the  beats,  but  this  is  entirely  independent  of  the  rate  of  faradisa- 
tion. Indeed,  as  a  rule,  the  heart  responds  by  fewer  beats  to  a  rapid 
than  to  a  slow  rate  of  stimulation. 

Although  nearly  all  our  information  on  this  subject  is  derived 
from  the  examination  of  the  hearts  of  cold-blooded  animals,  and 
mainly  from  the  heart  of  the  frog,  there  is  no  reason  to  suppose 
that  what  is  true  for  one  vertebrate  is  not  true  for  all-;  such  differences 


260  PHYSIOLOGY   OF  THE   HEART  [CH.  XXI. 

as  tdo  occur  are  differences  of  degree  and  detail  rather  than  of  kind, 
and  Wooldridge,  many  years  ago,  succeeded  in  performing  the 
Stannius  experiment  on  the  heart  of  a  mammal. 

The  Isolated  Heart. 

If  a  frog's  heart  is  simply  excised  and  allowed  to  remain  without 
being  fed,  it  ceases  to  beat  after  a  time  varying  from  a  few  minutes 
to  an  hour  or  so.  But  if  it  is  fed  with  a  nutritive  fluid,  it  will  con- 
tinue to  beat  for  many  hours.  Other  substances  such  as  drugs  may 
be  added  to  the  perfusion  fluid,  and  their  effects  noted.  The  fluid 
may  be  passed  through  the  heart,  and  the  apparatus  employed  may 
be  exemplified  by  the  following  diagram  of  Schdfer's  heart -plethys- 
mograph  (fig.  234).  A  frog's  heart  is  tied  on  to  the  end  of  a  perfusion 


FIG.  234.— Schafer's  Heart-plethysmograph. 

caimula,  one  tube  of  which  serves  for  the  fluid  to  enter,  the  other  for 
it  to  leave.  The  end  of  the  cannula  projects  into  the  ventricle ;  the 
frog's  heart,  it  should  be  remembered,  possesses  no  coronary  vessels ; 
the  spongy  texture  of  the  cardiac  tissue  enables  it  to  take  up  what  it 
requires  from  the  blood  in  its  interior. 

The  cannula  passes  through  the  well-fitting  stopper  of  an  air-tight 
vessel  containing  oil.  On  one  side  of  the  vessel  is  a  tube,  in  which 
a  lightly  moving  piston  is  fitted ;  to  this  a  writing-point  is  attached. 
The  piston  is  moved  backwards  and  forwards  by  the  changes  of 
volume  in  the  heart  causing  the  oil  to  alternately  recede  from  and 
pass  into  this  side  tube.  The  corresponding  tube  on  the  other  side 
can  be  opened  and  the  tube  with  the  piston  closed  when  one  wishes 
to  cease  recording  the  movements.  It  is  with  instruments  of  this 
kind  that  a  vast  amount  of  valuable  work  was  performed,  and  the 
name  of  the  late  Dr  Sydney  Einger  is  specially  connected  with 
investigations  of  drug  action  by  means  of  this  method. 

The  best  nutritive  fluid  to  employ  is  undoubtedly  the  natural 
fluid,  the  blood.  But  in  order  to  use  blood  there  are  practical 
difficulties ;  it  is  difficult,  for  instance,  to  obtain  much  blood  from  a 
frog;  it  is  difficult  to  prevent  it  from  clotting,  and  if  agents  are 
added  to  check  clotting,  such  agents  usually  act  deleteriously  in  the 
cardiac  tissue.  The  blood  of  another  animal  may  not  be  altogether 


CH.  XXI.]  THE   EXCISED   MAMMALIAN   HEART  261 

innocuous,  and  this  is  specially  the  case  if  that  blood  has  been  pre- 
viously whipped,  and  the  fibrin  removed.  Physiologists  therefore 
owe  Dr  Einger  a  deep  debt  of  gratitude  for  his  discovery  of  the 
solution  now  known  as  Ringer's  solution.  This  is  physiological  salt- 
solution  to  which  minute  quantities  of  calcium  and  potassium  salts 
have  been  added.  In  other  words,  the  inorganic  salts  in  the  propor- 
tion occurring  in  the  blood  will  maintain  cardiac  activity  for  a  long 
time  without  the  addition  of  any  organic  material.  These  salts  are 
not  nutritive  in  the  strict  sense,  but  they  constitute  the  stimulus  for 
the  heart's  action.  Howell  of  Baltimore  has  shown  that  such  an 
inorganic  mixture  is  especially  efficacious  in  throwing  the  sinus  or 
venous  end  of  the  heart  into  rhythmical  action.  The  normal 
stimulus  for  the  starting  of  the  heart-beat  is  thus  to  be  sought  in 
the  mineral  constituents  of  the  blood.  These  mineral  compounds  in 
solution  are  broken  up  into  their  constituent  ions;  and  of  these, 
sodium  ions  are  the  most  potent  in  maintaining  the  osmotic  con- 
ditions that  lead  to  irritability  and  contractility.  A  solution  of  pure 
sodium  chloride,  however,  finally  throws  the  heart  into  a  condition  of 
relaxation;  hence  it  is  necessary  to  mix  with  it  small  amounts  of 
calcium  ions  to  restrain  this  effect.  Potassium  is  not  absolutely 
necessary,  but  it  also  favours  relaxation  during  diastole.  Calcium,  on 
the  other  hand,  is  the  element  which  produces  contraction,  and  if 
present  alone  or  in  excess,  will  produce  an  intense  condition  of  tonic 
contraction  known  as  calcium  rigor. 

Some  physiologists  have  manifested  a  hesitation  in  accepting  the  simple  view 
that  the  various  kations  mentioned  actually  originate  the  heart-beat,  and  have 
advanced  the  hypothesis  that  they  influence  a  mysterious  factor  they  have  named 
the  inner  stimulus.  What  this  inner  stimulus  is,  is  entirely  unknown,  and  whether 
or  not  it  is  connected  with  one  or  more  of  Langley's  receptive  substances  is  equally 
a  matter  of  speculation.  If  it  exists  it  is  not  able  to  originate  cardiac  rhythm  in 
the  absence  of  the  appropriate  inorganic  salts. 

The  Excised  Mammalian  Heart. — During  the  past  few  years  it 
has  been  shown  that  the  mammalian  heart  can  also  be  kept  alive 
and  active  after  it  has  been  excised.  Valuable  as  the  results  have 
been  from  a  study  of  the  frog's  heart,  one  can  hardly  doubt  that 
those  which  one  hopes  to  obtain  in  the  future  from  a  similar  study 
of  the  mammal's  heart  will  be  still  more  important,  and  still  more 
trustworthy  for  the  drawing  of  deductions  useful  to  man.  Already 
the  new  method  has  shown  its  usefulness  not  only  in  reference  to 
the  metabolism  occurring  during  normal  cardiac  activity,  but  also 
from  the  pharmacological  point  of  view. 

In  order  to  maintain  the  action  of  the  excised  mammalian  heart 
certain  precautions  must  be  taken — 

1.  The  perfusion  fluid  must  be  maintained  at  or  about  body 
temperature  (37°  C.). 


262  PHYSIOLOGY   OF   THE   HEART  [CH.  XXI. 

2.  It  must  circulate  through  the  coronary  vessels. 

3.  It  must  be  well  oxygenated. 

As  before,  living  blood  is  the  ideal  fluid  for  perfusion,  but  the 
practical  difficulties  in  its  use  are  so  great,  that  a  modification  of 
Einger's  fluid  is  usually  employed.  On  this  fluid  the  heart  will 
continue  to  beat  for  many  hours,  but  it  will  beat  longer  (sometimes 
several  days)  if  a  little  dextrose  is  added  to  the  solution.  We  owe 
this  addition,  and  the  oxygenation  alluded  to  above,  to  Dr  Locke ; 
and  the  perfusion  fluid  now  universally  employed  is  consequently 
called  Locke's  solution.  This  has  the  following  composition:— 

Pure  distilled  water  .  .  .  .  100  c.c. 

Sodium  chloride  .  .  .  .  .  0'9  grammes. 

Potassium  chloride  .  .  .  .  .  0'042       „ 

Calcium  chloride  .  .  .  0'048 

Sodium  bicarbonate  •     .  .  .  .  0'02         ,, 

Dextrose  .  .  0'2 

Dr  Locke  has  tried  other  sugars  besides  dextrose,  but  no  other 
has  the  same  favourable  effect ;  Isevulose  is  better  than  most  other 
sugars,  but  not  nearly  so  good  as  dextrose.  Locke  and  Rosenheim 
have  further  shown  that  the  dextrose  is  used  up  during  cardiac 
activity,  and  this  lends  support  to  the  view  already  expressed  on  the 
importance  of  this  kind  of  sugar  as  a  source  of  muscular  energy 
(see  p.  131). 

A  mammal  such  as  a  cat  or  rabbit  is  killed  by  bleeding  or 
pithing.  The  heart  enclosed  in  the  pericardium  is  quickly  cut  out, 
and  gently  kneaded  to  free  it  from  blood,  in  some  warm  Einger's 
solution.  The  pericardium  is  then  dissected  off,  and  a  cannula  tied 
into  the  aorta;  this  is  connected  to  a  burette  which  is  kept  full  of 
Locke's  solution.  The  solution  must  be  maintained  at  body  tempera- 
ture, by  a  warm  water-jacket,  and  must  be  well  oxygenated  by  letting 
oxygen  bubble  through  it.  The  fluid  is  then  allowed  to  flow,  and  its 
pressure  closes  the  aortic  valves,  and  so  the  fluid  enters  the  coronary 
arteries,  and  escapes  from  the  right  auricle,  which  should  be  freely 
opened.  Under  these  circumstances  the  heart  will  continue  to  beat 
for  many  hours.  A  graphic  record  may  be  obtained  by  putting  a 
small  hook  into  the  apex,  and  attaching  this  by  a  thread  to  a  record- 
ing lever  beneath  it.  A  very  good  illustration  of  the  usefulness  of 
the  method  for  demonstrating  the  action  of  drugs  consists  in  adding 
a  small  amount  of  chloroform  to  the  circulating  fluid,  and  one  notices 
its  immediate  depressant  effect ;  on  the  other  hand,  a  minute  dose  of 
adrenaline  markedly  increases  the  rate  and  force  of  the  heart. 


CHAPTER  XXII 

THE   CIRCULATION   IN   THE   BLOOD-VESSELS 

THE  movement  of  the  blood  from  the  heart  through  the  arteries, 
capillaries,  and  veins  back  to  the  heart  again,  depends  on  a  number 
of  physical  factors;  and  in  the  consideration  of  this  important  subject 
we  shall  have  to  take  into  account  the  general  laws  which  regulate 
the  movement  of  fluids  in  tubes,  as  well  as  their  special  application 
to  the  flow  of  the  blood  in  the  blood-vessels. 

The  contraction  of  the  heart  is  the  primary  propelling  force,  and 
the  increase  of  pressure  which  is  thus  communicated  to  the  blood  it 
contains  causes  that  blood  to  enter  the  arteries ;  the  arterial  blood- 
pressure  is  higher  than  that  in  the  capillaries,  and  the  capillary 
pressure  is  higher  than  that  in  the  veins;  the  venous  pressure 
gradually  falls  as  we  approach  the  heart ;  it  is  lowest  of  all  in  the 
heart  cavities  during  diastole ;  fluid  moves  in  the  direction  of  lower 
pressure,  hence  the  flow  of  blood  is  from  the  heart  through  the 
vessels  back  to  the  heart  again. 

The  vessels  are  not  rigid  tubes,  but  possess  marked  elasticity ;  it 
is  owing  to  this  that  the  intermittent  force  of  the  heart  is  modified 
in  such  a  way  that  the  stream  of  blood  in  the  capillaries  is  a  constant 
one,  and  under  normal  circumstances  exhibits  no  pulsation  ;  the  pulse 
is  one  of  the  main  characters  of  the  arterial  flow.  A  further  com- 
plication is  due  to  the  fact  that  the  vessels  through  which  the  blood 
flows  are  of  varying  calibre,  and  this  is  the  main  factor  in  determin- 
ing its  velocity.  Every  time  an  artery  divides,  the  united  sectional 
area  of  its  branches  is  greater  than  that  of  the  parent  artery,  although, 
of  course,  each  of  the  individual  branches  is  of  smaller  calibre.  The 
total  bed  of  the  stream  is  thus  becoming  greater,  until  when  we 
reach  the  capillaries  the  bed  is  increased  suddenly  and  enormously, 
being  several  hundred  times  greater  than  that  of  the  aorta  from 
which  they  all  ultimately  spring.  In  the  case  of  the  veins  the  same 
is  true  in  the  reverse  direction ;  the  sectional  area  of  a  vein  is  less 
than  that  of  the  total  sectional  area  of  its  tributaries ;  hence  as  we 
approach  the  heart  the  total  bed  of  the  stream  is  becoming  continually 


264  THE   CIRCULATION    IN   THE   BLOOD-VESSELS  [CH.  XXII. 

smaller,  but  never  so  small  as  in  the  corresponding  arteries ;  a  vein 
is  always  twice  the  size,  often  more  than  twice  the  size,  of  the  cor- 
responding artery.  Velocity  of  flow  varies  inversely  with  the  bed 
of  the  stream ;  the  velocity  is  therefore  greatest  in  the  aorta,  slows 
down  in  the  small  arteries,  and  becomes  slowest  of  all  in  the  capil- 
laries where  the  total  bed  is  widest ;  we  may  compare  the  combined 
capillaries  to  a  vast  lake  into  which  the  arterial  river  flows.  On 
leaving  the  capillaries,  the  blood,  in  traversing  the  veins  once  more, 
becomes  accelerated  because  the  bed  of  the  stream  becomes  narrower, 
but  its  speed  in  a  vein  is  only  about  half  that  in  the  corresponding 
artery  because  the  bed  is  twice  as  great. 

In  connection  with  the  variation  in  the  bed  of  the  stream  we 
must  also  consider  the  question  of  resistance.  If  the  increase  in 
sectional  area  took  place  without  division  of  the  stream  into  numerous 
branches,  the  main  effect  would  be  to  lower  resistance  to  the  flow  of 
fluid ;  but  the  friction-lowering  effect  of  increased  area  is  much  more 
than  counterbalanced  by  the  increased  surface  of  the  numerous 
branches,  and  there  is  increased  friction  on  this  account.  The  resist- 
ance of  the  capillaries  would  be  large  even  for  a  stream  of  water, 
and  when  we  consider  that  the  blood  is  much  more  viscid  than  water, 
we  see  the  effect  must  be  much  greater.  The  resistance  to  the  flow 
of  fluid  along  a  small  tube  is  in  inverse  proportion  to  the  fourth 
power  of  the  diameter,  i.e.,  if  the  diameter  of  the  tube  is  halved,  the 
resistance  is  increased  sixteen-fold.  Between  the  arteries  and  the 
capillaries  are  the  small  arteries  or  arterioles ;  these  vessels  are 
always  in  a  state  of  moderate  or  tonic  constriction ;  they  may  roughly 
be  compared  to  narrow  inlets  into  the  wide  capillary  lake.  The 
main  resistance  to  the  passage  of  blood  through  the  tissues  is  situated 
in  the  arterioles,  and  not  in  the  capillaries ;  this  is  usually  spoken 
of  as  the  peripheral  resistance,  and  it  is  variable  by  alterations  in  the 
calibre  of  the  arterioles,  their  muscular  tissue  being  under  the  control 
of  nerves  which  are  termed  vaso-motor. 

The  main  resistance  is  in  the  arterioles  and  not  in  the  capillaries 
for  the  following  reason :  each  individual  capillary  is  small,  and  its 
resistance  therefore  great,  but  their  number  is  so  immense,  and  the 
total  bed  so  large,  that  the  resultant  resistance  offered  is  com- 
paratively small.  This  is  well  brought  out  by  a  comparison  of  the 
velocity  in  the  two  cases ;  in  the  arterioles  the  velocity  has  to  be 
high  in  order  to  supply  with  blood  the  large  capillary  areas  spring- 
ing from  them;  in  the  capillaries,  as  we  have  already  seen,  the 
velocity  is  low. 

After  this  general  account  of  the  main  features  of  the  circulation, 
we  can  now  pass  to  a  detailed  description  of  the  various  points 
raised. 


CH.  XXII.]  ELASTICITY   OF   THE   BLOOD-VESSELS  265 

Use  of  the  Elasticity  of  the  Vessels. 

If  a  puinp  is  connected  to  a  rigid  tube,  such  as  a  glass  tube, 
filled  with  water,  and  a  certain  amount  of  water  is  forced  into  the 
tube,  an  exactly  equal  amount  of  water  is  driven  out  from  the  open 
end.  During  the  intervals  of  pumping  the  flow  ceases,  accurately  at 
the  instant  the  inflow  stops.  If  in  the  next  place  the  open  orifice  is 
constricted  and  the  pumping  continued  as  before,  the  outflow  is  still 
restricted  to  the  time  during  which  water  is  being  driven  into  the 
tube.  The  only  difference  is  that  a  greater  force  of  pumping  will  be 
required  if  the  pump  is  to  empty  itself  in  the  same  time  as  before, 
and  the  force  required  will  increase  in  proportion  to  the  degree  of 
constriction  of  the  orifice,  until  with  a  fairly  considerable  constriction 
the  force  required  will  be  enormous. 

If  the  rigid  tube  is  replaced  by  an  elastic  one  with  a  wide  free 
opening,  the  outflow  will  again  be  intermittent  but  not  quite  restricted 
to  the  time  of  the  pumping.  This  latter  difference  is  because  the 
elastic  wall  of  the  tube  will  stretch  a  little  at  each  output  of  the 
pump,  and  this  continues  after  the  pump  has  ceased  to  discharge,  and 
will  then  recover,  at  the  same  time  driving  out  the  extra  small  amount 
of  fluid  it  contained,  after  the  pump  has  ceased  to  act.  The  flow  will 
thus  be  intermittent,  but  the  outflow  will  last  for  a  short  time 
longer  than  the  inflow.  If  now  the  orifice  be  diminished,  the  dura- 
tion of  the  outflow  will  begin  to  increase  still  further,  and,  as  the 
constriction  is  increased  more  and  more,  will  gradually  extend  over 
the  diastolic  period  of  the  pumping.  The  amount  of  work  required 
to  drive  the  fixed  volume  of  fluid  through  the  constricted  orifice  is 
the  same  with  a  rigid  and  with  an  elastic  tube.  In  the  former  case, 
however,  the  duration  of  the  outflow  is  of  necessity  the  same  as  that 
of  the  inflow,  whereas  in  the  second  case  this  time  is  prolonged.  If 
the  constriction  of  the  orifice  of  the  elastic  tube  is  sufficiently 
increased,  a  point  is  at  last  reached  at  which  the  outflow  lasts 
throughout  the  whole  cycle  of  the  pump,  and  here  therefore  some  of 
the  energy  imparted  to  the  fluid  by  the  pump  is  converted  into  a 
pressure  energy  represented  by  the  tension  of  the  elastic  walls  of  the 
tube,  and  this  energy  is  given  out  again  after  the  fluid  has  ceased  to 
enter  the  tube  and  is  just  sufficient  to  exactly  drive  out  the  stored 
fluid  during  the  resting  period,  and  a  point  will  ultimately  be  reached 
at  which  the  outflow  will  become  not  only  continuous  but  also 
constant.  The  degree  of  constriction  necessary  to  produce  this  effect 
will  depend  upon  the  distensibility  of  the  elastic  tube.  The  more 
distensible  this  is,  the  earlier  will  this  stage  be  reached,  and  the  lower 
will  be  the  mean  pressure.  This  is  the  condition  we  find  in  the 
circulatory  system. 

Let  us  now  apply  this  to  the  body. 


266  THE  CIRCULATION   IN   THE   BLOOD-VESSELS  [CH.  XXII. 

At  each  beat  the  left  ventricle  forces  about  three  ounces  of  blood 
into  the  already  full  arterial  system.  The  arteries  are  elastic  tubes, 
and  the  amount  of  elastic  tissue  is  greatest  in  the  large  arteries. 
The  first  effect  of  the  extra  three  ounces  is  to  distend  the  aorta  still 
further ;  the  elastic  recoil  of  the  walls  drives  on  another  portion  of 
blood,  which  distends  the  next  section  of  the  arterial  wall,  and  this 
distension  is  transmitted  as  a  wave  along  the  arteries,  but  with 
gradually  diminishing  force  as  the  total  arterial  stream  becomes 
larger.  This  wave  constitutes  the  pulse-wave.  Between  the  strokes 
of  the  pump,  or,  in  other  words,  during  the  periods  of  diastole,  the 
energy  imparted  to  the  elastic  arterial  walls  by  the  heart,  and  which 
has  produced  distension  of  the  arteries,  comes  into  play ;  their  recoil 
drives  the  blood  onwards  and  the  arteries  return  to  their  original  size. 
The  flow,  therefore,  does  not  cease  during  the  heart's  inactivity,  so 
that  although  the  force  of  the  heart  is  an  intermittent  one,  the  flow 
through  the  capillaries  and  the  veins  beyond  is  a  constant  one,  all 
trace  of  pulsation  having  disappeared.  The  peripheral  resistance 
which  keeps  up  the  blood-pressure  in  the  arteries,  and  like  the  con- 
striction at  the  end  of  our  india-rubber  tube,  assists  in  the  conversion 
of  the  intermittent  into  a  continuous  and  constant  stream,  is  to.  be 
found  in  the  arterioles  or  small  arteries,  just  before  the  blood  passes 
into  what  we  have  termed  the  vast  capillary  lake.  These  small 
arteries  with  their  relative  excess  of  muscular  tissue,  are  in  health 
always  in  a  state  of  moderate  tonic  contraction. 

The  large  arteries  contain  a  considerable  amount  of  muscular  as 
well  as  elastic  tissue.  This  co-operates  with  the  elastic  tissue  in 
adapting  the  calibre  of  the  vessels  to  the  quantity  of  blood  they 
contain.  For  the  amount  of  blood  in  the  vessels  is  never  quite 
constant,  and  were  elastic  tissue  only  present,  the  pressure  exercised 
by  the  walls  of  the  containing  vessels  on  the  contained  blood  would 
be  sometimes  very  small,  sometimes  too  great.  The  presence  of  a 
contractile  element,  however,  provides  for  a  certain  uniformity  in  the 
amount  of  pressure  exercised.  There  is  no  reason  to  suppose  that 
the  muscular  coat  assists  in  propelling  the  onward  current  of  blood, 
except  in  virtue  of  the  fact  that  muscular  tissue  is  elastic,  and  there- 
fore co-operates  in  the  large  arteries  with  the  elastic  tissue  in  keeping 
up  the  constant  flow  in  the  way  already  described. 

The  contractility  of  the  arterial  walls  fulfils  a  useful  purpose  in 
checking  haemorrhage  should  a  small  vessel  be  cut,  as  it  assists  in  the 
closure  of  the  cut  end,  and  this  in  conjunction  with  the  coagulation 
of  the  blood  arrests  the  escape  of  blood. 

Blood-pr  e  ssur  e . 

The  circulation  of  the  blood  depends  on  the  existence  of  different 
degrees  of  pressure  in  different  parts  of  the  circulatory  system ; 


CH.  XXII.]  BLOOD-PRESSURE  267 

there  is  a  diminution  of  pressure  from  the  heart  onwards  through 
arteries,  capillaries,  and  veins,  back  to  the  heart  again. 

Fig.  235  represents  roughly  the  fall  of  pressure  along  the  systemic 
vascular  system. 

It  falls  slowly  in  the  great  arteries  and  manifests  oscillations 
corresponding  with  the  alternate  systole  and  diastole  of  the  heart ; 
at  the  end  of  the  arterial  system  it  falls  suddenly  and  extensively  in 
the  course  of  the  arterioles  ;  it 
again  falls  gradually  through 
the  capillaries  and  veins  till  in 
the  large  veins  near  the  heart 
it  is  negative.  Such  a  diagram 
of  blood-pressure  is  thus  very 
different  from  one  of  velocity ; 
the  velocity  like  the  pressure 

falls  from  the  arteries  to  the      °LV~  A  c  v 

capillaries  but  unlike  it,  rises   Fm  235._Height  of  blood.pressure  (BP)  in  LV,  ^ 

again  in  the  Veins.  ventricle.     A,    arteries ;    C,    capillaries  ;    V,    veins ; 

We  must  now  study  the 

methods  by  which  blood-pressure  is  measured  and  recorded,  and  the 
main  causes  that  produce  variations  in  its  amount. 

In  order  that  we  may  understand  the  methods  that  are  used  for 
this  purpose,  it  will  be  first  necessary  for  us  to  consider  some  of  the 
general  laws  of  fluid  pressure,  and  then  to  study  the  methods  that 
are  employed  in  an  artificial  schema  of  the  circulation. 

Fluid  pressure  is  a  different  thing  from  the  pressure  of  a  solid, 
and  is  exercised  equally  in  all  directions.  If  a  cylindrical  vessel, 
placed  vertically,  is  filled  with  a  cylinder  of  ice,  the  pressure  of  the 
ice  will  be  exercised  on  the  bottom  of  the  cylinder,  but  not  on  its 
sides.  When  the  ice  melts,  the  water  presses  on  the  sides  also,  and 
if  a  hole  is  made  in  the  cylinder  below  the  level  of  the  upper  surface 
of  the  water,  the  water  will  flow  out  of  the  hole,  and  the  force  with 
which  it  escapes  will  be  proportional  to  the  depth  of  the  hole  beneath 
the  surface.  If  we  take  a  square  centimetre  as  the  unit  of  area,  the 
actual  pressure  exerted  on  it  is  h  x  d  x  g,  where  h  is  the  height  of  the 
free  surface  above  the  level  where  we  are  measuring  the  pressure,  d 
the  density  of  the  fluid,  and  g  the  acceleration  of  gravity  (981). 
Suppose  a  gramme  of  water  to  flow  out,  we  may  consider  that  this 
gramme  has  fallen  through  a  height  or  head  h  in  centimetres  from 
the  free  surface  to  the  opening ;  it  comes  practically  from  the  top, 
because  it  is  there  that  the  liquid  disappears  from  inside  the  vessel. 
In  falling  the  height  k,  it  gives  out  hg  ergs  of  work. 

The  unit  of  force  is  called  a  dyne ;  a  moving  body  is  said  to  possess 
momentum  :  this  is  measured  by  the  product  of  its  mass  and  its  velocity  ;  thus  the 
effective  quantity  of  motion  of  a  body  may  be  large  on  account  of  its  having  a  large 


268  THE   CIRCULATION   IN   THE   BLOOD-VESSELS  [CH.  XXII. 

mass  (for  instance,  a  heavy  waggon  rolling  down  a  hill),  or  large  velocity  (for  instance, 
a  bullet  speeding  through  the  air).  A  force  continuously  applied  to  a  moving  mass 
produces  a  continuous  increase  in  its  rate  of  movement  ;  this  is  termed  acceleration, 
and  force  may  be  defined  as  the  rate  of  change  of  momentum  ;  it  can  be  measured, 
therefore,  by  observing  the  amount  of  momentum  it  generates  in  a  measured  time, 
and  dividing  by  that  time.  If  a  gramme  is  taken  as  the  unit  of  mass,  a  centimetre 
as  the  unit  of  length,  and  a  second  as  the  unit  of  time,  the  unit  of  force 

_  momentum   _  gramme-centimetre  per  second 

Time.  Time  in  seconds. 

=  gramme-centimetre  per  second,  per  second  =  1  dyne. 

The  unit  which  corresponds  to  the  dyne  in  the  measurement  of  work  is  called  an 
erg,  that  is,  the  work  done  in  lifting  a  gramme  weight  through  the  height  of  one 
centimetre  ;  the  weight  of  a  gramme  is  981  dynes,  and  the  work  done  in  lifting  it 
one  centimetre  is  981  ergs. 

The  kinetic  energy  of  a  body  moving  with  velocity  v  is  £  x  mass 
or  for  one  gramme  Jv2;  hence  if  all  the  work  that  liquid  can  do 
is  spent  in  giving  kinetic  energy  to  it,  the  velocity  with  which  it  will 
flow  out  is  given  by  putting  the  kinetic  energy  =  work  done.     In 
other  terms  :  — 

=    h  ;  hence  v  =      lh  or  h  =  !L 


A  liquid,  however,  has  not  necessarily  a  free  surface,  but  may  be 
completely  enclosed,  as  is  the  water  in  a  system  of  hydraulic  pressure 
mains,  or  the  blood  in  the  circulatory  system.  The  pressure  in  such 
a  system  at  any  point  may  be  measured  by  inserting  at  that  point 
a  vertical  tube  at  right  angles  to  the  blood-vessel  ;  the  blood  would 
rise  in  it  to  a  point,  and  would  form  a  free  surface  a  certain  distance 
up  this  tube  ;  the  head  h  in  the  above  calculation  must  be  reckoned 
from  this  free  surface  downwards.  If,  instead  of  using  a  tube  of  fine 
bore  for  this  purpose,  we  employ  a  wider  tube,  say  of  ten  times 
greater  area,  the  height  or  head  to  which  the  fluid  rises  will  be  the 
same  as  in  the  narrow  tube,  though  naturally  the  actual  weight  of 
fluid  supported  will  be  ten  times  greater  ;  but  the  weight  per  unit  of 
area  is  the  same  in  both  cases.  When,  therefore,  we  measure  the 
pressure  of  fluid  in  terms  of  the  height  of  a  column  of  fluid,  such  as 
mercury,  which  it  will  balance,  we  really  mean  that  the  force  of  the 
blood  is  equal  to  the  weight  of  the  mercury  it  supports  per  unit  of 
area,  and  this  will  naturally  be  proportional  to  the  height  of  the 
column. 

Let  us  next  consider  the  simple  case  of  a  fluid  flowing  from  a 
reservoir,  E  (fig.  236),  along  a  tube,  which  we  will  imagine  is  open  at 
the  other  end. 

In  the  course  of  the  tube  we  will  suppose  three  upright  glass 
tubes  (A,  B,  and  D)  are  inserted  at  equal  distances.  Between  B  and 
D  there  is  a  bladder,  which  may  be  divided  into  a  number  of  channels 
by  packing  it  with  tow  to  represent  the  capillaries,  and  between  B  and 


CH.  XXII.] 


SCHEMA   OF   THE   CIRCULATION 


269 


C,  a  clip  E,  which  can  be  tightened  or  loosened  at  will,  and  which 
will  roughly  represent  the  peripheral  resistance  produced  by  the 
arterioles.  The  far  end  of  the  tube  is  provided  with  a  stop-cock.  If 
this  stop-cock  is  closed  there  will  naturally  be  no  flow  of  fluid,  and 
the  fluid  will  rise  to  equal  heights  indicated  by  the  dotted  line  in  all 
the  upright  tubes.  This  shows  that  the  pressure  in  all  parts  of  the 
tube  is  the  same.  The  upright  tubes  which  measure  the  lateral 
pressure  exerted  by  the  fluid  on  the  wall  of  the  main  tube,  are  called 
pizometers,  manometers,  or  pressure  measurers. 

If  now  the  stop-cock  is  opened,  the  fluid  flows  on  account  of  the 
difference  of  pressure  brought  about  by  gravitation ;  the  height  of  the 


FIG.  236. — Schema  to  illustrate  blood-pressure. 

fluid  in  the  manometers  indicates  that  the  pressure  is  greatest  in  R, 
less  in  A,  less  still  in  B,  and  least  of  all  in  D. 

On  account  of  the  peripheral  resistance  of  the  arterioles  and 
capillaries,  the  pressure  is  very  small  in  the  veins,  as  indicated  by  the 
height  of  the  fluid  in  the  manometer  D.  The  difference  between  D 
and  B  is  much  more  marked  than  the  difference  between  B  and  A. 
If  the  fluid  which  flows  out  of  the  end  of  the  tube  is  collected  in  a 
jug  and  poured  back  into  R,  we  complete  the  circulation.  But  the 
schema  is  an  extremely  rough  one,  and  is  especially  faulty  in  that  the 
pressure  which  starts  at  R  is  nearly  constant  and  not  intermittent. 
This  may  be  remedied  by  taking  R  in  the  hand,  and  raising  and  lower- 
ing it  alternately.  The  fluid  in  the  manometers  bobs  up  and  down 
with  every  rise  and  fall  of  R :  this  is  least  marked  in  D.  The  greater 
and  the  faster  the  movement  of  R,  the  greater  is  the  rise  of  arterial 
pressure.  This  is  a  rough  illustration  of  the  fact  that  increase  in 


270 


THE   CIRCULATION    IN   THE   BLOOD-VESSELS  [CH.  XXII. 


the  force  and  frequency  of  the  heart's  beat  causes  a  rise  of  arterial 
pressure. 

Again,  if  more  fluid  is  poured  into  E,  there  is  a  correspond- 
ing rise  in  fluid  in  the  manometers.  This  illustrates  the  rise  of 
pressure  produced  by  an  increase  in  the  contents  of  the  vascular 
system. 

And  this  schema,  rough  though  it  is,  also  serves  to  illustrate  the 
third  important  factor  in  the  maintenance  of  the  blood-pressure, 
namely,  the  peripheral  resistance.  This  is  done  by  means  of  the  clip 
E ;  if  the  clip  is  tightened,  one  imitates  increased  constriction  of  the 
arterioles ;  if  it  is  loosened,  one  imitates  dilatation  of  the  arterioles. 
If  it  is  closed  entirely,  the  fluid  in  A  and  B  rises  to  the  same  level  as 
that  in  E ;  the  pressure  of  E  is  not  felt  at  all  by  C  and  D,  which 
empty  themselves,  and  the  flow  ceases.  If  the  clip  E  is  only  tightened 
so  as  not  to  be  quite  closed,  the  arterial  pressure  (in  A  and  B)  rises, 
and  the  venous  pressure  (in  D)  falls ;  if  the  clip  is  freely  opened,  the 
arterial  pressure  falls,  and  the  venous  pressure  rises. 

These  same  facts  can  be  demonstrated  by  a  more  perfect  circula- 
tion schema,  such  as  is  represented  in  fig.  237. 


AUo' 


FIG.  237.— Schema  of  the  circulation. 

The  heart  (H)  is  represented  by  a  Higginson's  syringe,  which  is 
worked  with  the  hand  ;  the  tube  from  it  represents  the  arterial  system, 
the  clip  E  the  resistance  of  the  arterioles ;  C  is  the  capillary  lake, 
from  which  the  vein  (larger  than  the  artery)  leads  back  to  the  heart 
H.  A  and  B  are  two  manometers  which  respectively  indicate  arterial 
and  venous  pressures.  Only  in  place  of  straight  tubes  mercurial 
manometers  are  used.  Each  of  these  is  a  |J~tube  about  half  filled 
with  mercury,  and  united  to  the  artery  or  vein  by  a  tube  containing 
fluid.  If  the  mercury  in  the  two  limbs  of  the  U  is  at  the  same  level, 
the  pressure  of  the  fluid  in  connection  with  one  limb  is  exactly  equal  to 


en.  XXIL] 


STEPHEN    HALES     EXPERIMENTS 


271 


that  exerted  by  the  atmospheric  pressure  on  the  other.  The  mercury, 
however,  is  pushed  up  in  the  far  limb  of  the  manometer  connected  to 
the  artery,  the  pressure  there  being  greater  than  that  of  the  atmos- 
phere ;  this  is  therefore  called  positive  pressure,  and  the  total  amount 
of  pressure  is  measured  by  the  difference  between  the  levels  a  and  a. 
The  manometer  B  attached  to  the  vein,  however,  indicates  a  negative 
pressure  (b  V),  that  is  a  pressure  less  than  that  of  the  atmosphere,  so 
that  the  mercury  in  the  limb  nearest  the  vein  is  sucked  up. 

Anderson  Stuart's  kymoscope  (fig.  238)  is  a  more  complete  schema. 
It  consists  of  a  long  leaden  tube  filled  with  fluid,  the  two  ends  of 
which  are  connected  by  an  india-rubber 
tube  on  which  is  a  valved  syringe  to 
represent  the  heart  On  the  course  of 
the  tube  are  a  large  number  of  open- 
mouthed  upright  manometers  which 
indicate  the  pressure  when  the  syringe 
is  worked,  and  confer  on  the  tube  the 
elasticity  necessary  to  cause  the  dis- 
appearance of  the  pulse  in  the  middle 
region  which  represents  the  capillaries. 
The  long  leaden  tube  is  twisted  round 
a  cylinder,  so  that  the  manometers  are 
placed  closely  side  by  side. 

We  can  now  pass  on  to  the  methods 
adopted  in  the  investigations  of  blood- 
pressure  in  animals. 

The  fact  that  the  blood  exerts 
considerable  pressure  on  the  arterial 
walls  may  be  readily  shown  by 
puncturing  any  artery;  the  blood  is 
propelled  with  great  force  through 
the  opening,  and  the  jet  rises  to  a 
considerable  height;  in  the  case  of  a 
small  artery,  where  the  pressure  is 
lower,  the  jet  is  not  so  high  as  in  a  large  artery :  the  jerky  character 
of  the  outflow  due  to  the  intermittent  action  of  the  heart  is  also 
seen.  If  a  vein  is  similarly  injured,  the  blood  is  expelled  with  much 
less  force,  and  the  flow  is  continuous,  not  intermittent. 

The  first  to  make  an  advance  on  this  very  rough  method  of 
demonstrating  blood-pressure  was  the  Rev.  Stephen  Hales,  vicar  of 
Teddington  (1702).  He  inserted,  using  a  small  brass  tube  as  a 
cannula,  a  glass  tube  at  right  angles  to  the  femoral  artery  of  a  horse, 
and  noted  the  height  to  which  the  blood  rose  in  it.  This  is  a  method 
like  that  which  we  used  in  the  first  schema  described  (fig.  236).  The 
blood  rose  to  the  height  of  about  8  feet,  and  having  reached  its  highest 


FIG.  238.— Anderson  Stuart's 
Kymoscope. 


272 


THE   CIRCULATION   IN   THE   BLOOD-VESSELS  [CH.  XXII. 


point,  it  oscillated  with  the  heart-beats,  each  cardiac  systole  causing 
a  rise,  each  diastole  a  fall.  Hales  also  noted  a  general  rise  during 
each  inspiration.  The  method  taught  Hales  these  primary  truths  in 
connection  with  arterial  pressure,  but  it  possesses  many  disadvan- 
tages ;  in  the  first  place,  the  blood  in  the  glass  tube  very  soon  clots, 
and  in  the  second  place,  a  column  of  liquid  8  feet  high  is  an 
inconvenient  one  to  work  with. 

The  first  of  these  disadvantages  was  overcome  to  a  great  extent 
by  Vierordt,  who  attached  a  tube  filled  with  saturated  solution  of 
sodium  carbonate  to  the  artery,  and  the  blood-pressure  was  measured 
by  the  height  of  the  column  of  this  saline  solution  which  the  blood 
would  support. 

The  second  disadvantage  was  overcome  by  Poiseuille,  who  intro- 
duced the  heavy  liquid,  mercury,  as  the  substance  on  which  the  blood 
exerted  its  pressure;  and  the  U-shaped  mercurial  manometer  was 
connected  to  the  artery  by  a  tube  filled  with  sodium  carbonate 
solution  to  delay  clotting. 

The  study  of  blood-pressure  cannot,  however,  be  considered  to 
have  been  in  a  satisfactory  condition  until  the  introduction  by  Carl 


A 


B 


FIG.  239. — Diagram  of  mercurial  Kymograph. 


Ludwig  of  the  Kymograph;  that  is  to  say,  Poiseuille's  hcemodyna- 
mometer  was  combined  with  apparatus  for  obtaining  a  graphic  record 
of  the  oscillations  of  the  mercury.     The  name  kymograph  or  wave- 
writer,  we  shall  see  immediately,  is  a  very  suitable  one. 
A  skeleton  sketch  of  the  apparatus  is  given  in  fig.  239. 


CH.  XXII.]  THE    KYMOGRAPH  273 

The  artery  is  exposed  and  clamped,  so  that  no  haemorrhage 
occurs ;  it  is  then  opened,  and  a  glass  cannula  is  inserted  and  firmly 
tied  in.  The  form  of  cannula  usually  employed  (Francois  Franck's) 
is  shown  on  a  larger  scale  at  A ;  the  narrow  part  with  the  neck  in  it 
is  tied  into  the  artery  towards  the  heart ;  the  cross  piece  of  the  T  is 
united  to  the  manometer;  the  third  limb  is  provided  with  a  short 
piece  of  india-rubber  tubing  which  is  kept  closed  by  a  clip  and  only 
opened  on  emergencies,  such  as  to  clear  out  a  clot  with  a  feather 
should  one  form  in  the  cannula  during  the  progress  of  an  experiment. 

The  tube  by  means  of  which  the  cannula  is  united  to  the  man- 


FIG.  240.—  The  manometer  of  Ludwig's  Kymograph.  It  is  also  shown  in  fig.  241,  D,  C,  E.  The 
mercury  which  partially  fills  the  tube  supports  a  float  in  the  form  of  a  piston,  nearly  filling  the 
tube  ;  a  wire  is  iixed  to  the  float,  and  the  writing  style  or  pen  fixed  to  the  wire  is  guided  by  passing 
through  the  brass  cap  of  the  tube  ;  the  pressure  is  communicated  to  the  mercury  by  means  of  a 
flexible  metal  tube  fille 


led  with  fluid. 


ometer  is  not  an  elastic  one,  but  is  made  of  flexible  metal  or  thick 
rubber,  so  that  none  of  the  arterial  force  may  be  wasted  in  expanding 
it.  The  tube,  cannula,  and  proximal  limb  of  the  manometer  are  all 
filled  with  a  saturated  solution  of  sodium  carbonate,  sodium  sulphate, 
or  other  salt  which  will  mix  with  blood  and  delay  its  clotting.  Before 
the  clip  is  removed  from  the  artery,  the  pressure  is  first  got  up  by  a 
syringe  (or  pressure  bottle  containing  the  same  saline  solution  sus- 
pended at  a  good  height  above  the  apparatus  and  connected  to  it  by 
a  tube),  so  that  the  mercury  rises  in  the  distal  limb  to  a  height  greater 
than  that  of  the  anticipated  blood-pressure  ;  this  prevents  blood  pass- 
ing into  the  cannula  when  the  arterial  clip  is  removed. 

In  the  distal  limb  of  the  (J'tube,  floating  on  the  surface  of  the 

s 


274 


THE   CIRCULATION    IN    THE   BLOOD-VESSELS  [CH.  XX11. 


mercury,  is  an  ivory  float,  from  which  a  long  steel  wire  extends 
upwards,  and  terminates  in  a  stiff  piece  of  parchment  or  a  bristle 
which  writes  on  a  moving  surface  covered  with  smoked  paper.  When 
the  two  limbs  of  the  mercury  are  at  rest,  the  writing-point  inscribes 
a  base-line  or  abscissa  on  the  travelling  surface ;  when  the  pressure 
is  got  up  by  the  syringe  it  writes  a  line  at  a  higher  level.  When 
the  arterial  clip  is  removed  it  writes  waves  as  shown  in  the  diagram 


PIG.  241. — Diagram  of  mercurial  Kymograph.  A,  revolving  cylinder,  worked  by  a  clockwork  arrange- 
ment contained  in  the  box  (B),  the  speed  being  regulated  by  a  fan  above  the  box ;  the  cylinder  is 
supported  by  an  upright  (b),  and  is  capable  of  being  raised  or  lowered  by  a  screw  (a),  by  a  handle 
attached  to  it;  D,  C,  E,  represent  the  mercurial  manometer,  which  is  shown  on  a  larger  scale  in 
fig.  240. 

(fig.  239),  the  large  waves  corresponding  to  respiration  (the  rise  of 
pressure  in  most  animals  accompanying  inspiration),*  the  smaller 
ones  to  the  individual  heart-beats.  The  blood-pressure  is  really 
twice  as  great  as  that  indicated  by  the  height  of  the  tracing  above 
the  abscissa,  because  if  the  manometer  is  of  equal  bore  throughout, 
the  mercury  falls  in  one  limb  the  same  distance  that  it  rises  in  the 
other;  the  true  pressure  is  measured  by  the  difference  of  level 
between  a  and  a  (fig.  239). 

*  The  explanation  of  the  respiratory  curves  on    the  tracing  is  postponed  till 
after  we  have  studied  Respiration. 


CH.  XXIL] 


VENOUS    BLOOD-PKESSUKE 


275 


Fig.  240  shows  a  more  complete  view  of  the  manometer,  and 
fig.  241  is  a  diagram  of  the  arrangement  by  means  of  which  it  is 
made  into  a  kymograph. 

Fig.  242  shows  a  typical  normal  arterial  blood-pressure  tracing  on 
a  larger  scale. 


KIG.  242.— Normal  tracing,  somewhat  magnified,  of  arterial  pressure  in  the  rabbit  obtained  with  the 
mercurial  kymograph.  The  smaller  undulations  correspond  with  the  heart-beats,  the  larger  curves 
with  the  respiratory  movements.  The  abscissa  or  base-line,  which  on  this  scale  would  be  several 
inches  below  the  tracing,  is  not  shown.  (Burdon-Sanderson.) 

Iii  taking  a  tracing  of  venous  Hood-pressure,  the  pressure  is  so  low 
and  corresponds  to  so  few  millimetres  of  mercury,  that  a  saline 
solution  is  usually  employed  instead  of  mercury.  If  the  vein  which 


FIG.  243.— A  form  uf  Kirk's  Spring  Kymograph,  a,  Tube  to  be  connected  with  artery  ;  c,  hollow  spring, 
the  movement  of  which  moves  b,  the  writing  lever ;  e,  screw  to  regulate  height  of  b ;  d,  outside 
protective  spring ;  g,  screw  to  lix  on  the  upright  of  the  support. 

is  investigated  is  near  the  heart,  a  venous  pulse  is  exhibited  on  the 
tracing,  with  small  waves  as  before  corresponding  to  heart-beats,  and 


276 


THE   CIRCULATION   IN  THE    BLOOD-VESSELS  [CH.  XXII. 


larger  waves  to  respiration,  only  the  respiratory  rise  in  pressure  now 
accompanies  expiration. 

The  capillary  pressure  is  estimated  by  the  amount  of  pressure 
necessary  to  blanch  the  skin ;  this  has  been  done  in  animals  and  men 
(v.  Kries,  Roy  and  Brown). 

Other  manometers  are  often  employed  instead  of  the  mercurial 
one.  Fick's  is  one  of  these.  The  blood-vessel  is  connected  as  before 
with  the  manometer,  and  the  pressure  got  up  by  the  use  of  a  syringe 


FIG.  244.— Fick's  Kymograph,  improved  by  Bering  (after  M'Kendrick).  a,  Hollow  spring  tilled  with 
alcohol,  bearing  lever  arrangement  b,  d,  c,  to  which  is  attached  the  marker  e ;  the  rod  c  passes 
downwards  into  the  tube/,  containing  castor  oil,  which  offers  resistance  to  the  oscillations  of  c; 
g,  syringe  for  filling  the  leaden  tube  h  with  saturated  sulphate  of  sodium  solution,  and  to  apply 
sufficient  pressure  as  to  prevent  the  blood  from  passing  into  the  tube  h  at  i,  the  cannula  inserted 
into  the  vessel;  I,  abscissa-marker,  which  can  be  applied  to  the  moving  surface  by  turning  the 
screw  m ;  k,  screw  for  adjusting  the  whole  apparatus  to  the  moving  surface  ;  o,  screw  for  elevating 
or  depressing  the  Kymograph  by  a  rack-and-pinion  movement ;  n,  screw  for  adjusting  the  position 
of  the  tube/. 

(which  is  seen  in  fig.  244,  g),  before  the  clip  is  removed  from  the 
artery.  The  manometer  itself  is  a  hollow  C -shaped  spring  filled  with 
liquid ;  this  opens  with  increase,  and  closes  with  decrease  of  pressure, 
and  the  movements  of  the  spring  are  communicated  to  a  lever  pro- 
vided with  a  writing-point. 

Hurthle's  manometer  (see  p.  242)  is  also  very  much  used.  The 
advantage  of  these  forms  of  manometer  is  that  the  character  and 
extent  of  each  pressure  change  is  much  better  seen.  In  a  mercury 


CH.  XXII.]  VARIATIONS   OF   BLOOD-PRESSURE  277 

manometer  the  inertia  is  so  great  that  it  cannot  respond  to  the  very 
rapid  variations  in  pressure  which  occur  within  an  artery  during  each 
cardiac  cycle.  If  Fick's  or  Hiirthle's  manometer  is  employed,  and 
the  surface  travels  sufficiently  fast,  these  can  be  recorded  (see  fig. 
245).  These  instruments,  though  useful  for  recording  the  complete 


FIG.  245. — Normal  arterial  tracing  obtained  with  Fick's  Kymograph  in  the  dog. 
(Burdon-Sanderson . ) 

changes  in  pressure,  require  calibration :  that  is,  the  extent  of  move- 
ment that  corresponds  to  known  pressures  must  be  ascertained  by 
actual  experiment.  They  teach  us  that  the  highest  pressure  reached 
during  systole  may  be  twice  or  thrice  the  lowest  attained  during 
diastole.  . 

The  following  table  gives  the  probable  average  height  of  blood- 
pressure  in  various  parts  of  the  vascular  system  in  man.  They  have 
been  very  largely  inferred  from  experiments  on  animals : — 

Large  arteries  (e.g.  carotid)  (  +  14°  mm'  <>bout  6  inches) 

I          mercury. 

Medium  arteries  (e.g.  radial)      .         +110  mm.  mercury. 
Capillaries          .          .          .   +  15  to  +     20     „ 
Small  veins  of  arm    .          .  +        9     „ 

Portal  vein  .  .  .  .  +  10  „ 
Inferior  vena  cava  .  .  .  +  3  „ 
Large  veins  of  neck  from  0  to  -  8  „ 

(Starling.) 

These  pressures  are,  however,  subject  to  considerable  variations ; 
the  principal  factors  that  cause  variation  are  the  following : — 
Increase  of  arterial  blood-pressure  is  produced  by — 

1.  Increase  in  the  rate  and  power  of  the  heart-beat. 

2.  Increase  in  the  contraction  of  the  arterioles. 

3.  Increase  in  the  total  quantity  of  blood  (plethora,  after  a  meal, 

after  transfusion). 
Decrease  in  the  arterial  blood-pressure  is  produced  by — 

1.  Decrease  in  the  rate  and  force  of  the  heart-beat. 

2.  Decrease  in  the  contraction  of  the  arterioles. 

3.  Decrease  in  the  quantity  of  blood  (e.g.  after  haemorrhage). 

The  above  is  true  for  general  arterial  pressure;  but  if  we  are 
investigating  local  arterial  pressure  in  any  organ,  the  increase  or 


278  THE   CIRCULATION    IN    THE   BLOOD-VESSELS  [CH.  XXII. 

decrease  in  the  size  of  the  arterioles  of  other  areas  may  make  its 
effect  felt  in  the  special  area  under  investigation. 

Venous  pressure  varies  directly  with  the  volume  of  the  blood  ;  in 
the  arteries  the  effect  of  increase  of  fluid  is  slight  and  temporary, 
owing  to  the  rapid  adaptability  of  the  peripheral  resistance;  the 
excess  of  fluid  collects  in  and  distends  the  easily  dilatable  venous 
reservoir.  With  regard  to  the  first  and  second  factors  in  the  fore- 
going table,  venous  pressure  varies  in  the  opposite  way  to  arterial 
pressure. 

It  is  easy  to  understand  how  this  is ;  when  the  rate  of  the  heart 
increases,  the  total  volume  of  blood  discharged  into  the  aorta  per 
second  is  increased ;  similarly,  an  increase  in  the  force  of  the  beat 
also  results  in  an  increase  in  the  cardiac  output,  and  in  both  cases 
a  more  rapid  and  complete  emptying  of  the  auricle  is  produced.  This 
is  felt  throughout  the  whole  of  the  pulmonary  circulation,  and  the 
accelerated  flow  therefore  causes  a  fall  in  the  venous  pressure.  If, 
however,  the  rise  of  pressure  is  due  to  a  contraction  of  the  arterioles, 
a  stage  may  be  reached  in  which  the  heart  is  no  longer  able  to  over- 
come the  high  pressure  produced.  It  then  fails  to  empty  itself,  and 
the  bloo4  is  dammed  up  on  the  venous  side,  i.e.  the  venous  pressure 
rises. 

With  regard  to  the  arterioles,  contraction  means  a  rise  in  arterial 
pressure,  because  while  the  amount  sent  into  the  arteries  remains  the 
same  the  outflow  into  the  capillaries  is  cut  down.  More  blood  is 
therefore  retained  in  the  arteries ;  they  become  more  distended  and 
the  pressure  rises.  The  first  effect  of  this  upon  the  venous  pressure 
will  be  to  diminish  it,  because  if  more  blood  is  retained  in  the  arteries 
there  is  less  for  the  veins  and  capillaries.  The  flow  into  the  veins  is 
thus  decreased,  and  the  venous  pressure  therefore  falls.  Moreover, 
the  heart  usually  responds  to  a  rise  in  pressure  by  increasing  its  force 
and  rate,  and  consequently  more  blood  is  taken  from  the  veins  near 
the  heart.  For  both  reasons,  then,  the  venous  pressure  will  fall,  but 
that  fall  is  limited,  as  pointed  out  above,  to  such  an  increase  only  as 
the  heart  is  capable  of  overcoming  successfully. 

Capillary  pressure  is  increased  by — 

1.  Dilatation  of  the  arterioles;   the  blood-pressure  of   the  large 
arteries  is  then  more  readily  propagated  into  them. 

2.  The  size  of   the   arterioles   remaining  the   same,  increase   of 
arterial  pressure  from  any  other  cause  will  produce  a  rise  of  capillary 
pressure. 

3.  By  narrowing  the  veins  leading  from  the  capillary  area ;  com- 
plete  closure   of   the   veins  may  quadruple  the  capillary  pressure. 
This  leads  -secondarily  to  an  increased  formation  of  lymph  (dropsy) ; 
as  when  a  tumour  presses  on  the  veins  coming  from  the  legs. 

4.  Any  circumstance  that  leads  to  increased  pressure  in  the  veins 


CH.  XXII.]  EFFECT   OF   GRAVITY  279 

will  act  similarly;  this  is  illustrated  by  the  effects  produced  by 
gravity  on  the  circulation,  as  in  alterations  of  posture. 

Capillary  pressure  is  decreased  by  the  opposite  conditions. 

Capillary  pressure  is  much  more  influenced  by  changes  in  the 
venous  pressure,  than  by  changes  in  the  arterial  pressure,  since  there 
is  between  the  arteries  and  capillaries  the  variable  and  usually  un- 
known peripheral  resistance  of  the  arterioles. 

Effect  of  gravity  on  the  circulation. — The  main  effect  of  gravity  is 
that  the  veins  are  filled  with  blood  in  the  part  which  is  placed  down. 
Thus,  if  an  animal  is  placed  suddenly  with  its  legs  hanging  down,  less 
blood  will  go  to  the  heart,  and  the  blood-pressure  in  the  arteries  will 
fall  temporarily  in  consequence.  This  hydrostatic  effect  of  gravity  is 
soon  overcome  by  an  increased  constriction  of  the  vessels  of  the 
splanchnic  area,  when  the  vaso-motor  mechanism  is  working  normally. 
The  efficient  action  of  the  "  respiratory  pump  "  is  also  of  importance 
in  counteracting  gravity. 

A  very  striking  illustration  of  the  effect  of  gravity  on  the  circula- 
tion can  be  demonstrated  on  the  eel.  The  animal  is  anaesthetised, 
and  a  small  window  is  made  in  the  body  wall  to  expose  the  heart. 
If  the  animal  is  then  suspended  tail  downwards,  the  beating  heart  is 
seen  to  be  empty  of  blood ;  all  the  blood  accumulates  in  the  tail  and 
lower  part  of  the  body ;  the  animal  has  no  "  respiratory  pump,"  such 
as  a  mammal  possesses,  to  overcome  the  effects  of  gravity.  If,  how- 
ever, the  animal,  still  with  its  tail  downwards,  be  suspended  in  a 
tall  vessel  of  water,  the  pressure  of  the  water  outside  its  body 
enables  it  to  overcome  the  hydrostatic  effect  of  gravitation,  and 
the  heart-cavities  once  more  fill  with  blood  during  every  diastole. 
Another  experiment  was  originally  performed  by  Salathe  on  a 
"  hutch "  rabbit.  If  the  animal  is  held  by  the  ears  with  its  legs 
hanging  down,  it  soon  becomes  unconscious,  and  if  left  in  that  position 
for  about  half  an  hour  it  will  die.  This  is  due  to  anaemia  of  the 
brain ;  the  blood  accumulates  in  the  very  pendulous  abdomen  which 
such  domesticated  animals  acquire,  and  the  vaso-motor  mechanism  of 
the  splanchnic  area  is  deficient  in  tone,  and  cannot  be  set  into  such 
vigorous  action  as  is  necessary  to  overcome  the  bad  effects  of  gravity. 
Consciousness  is,  however,  soon  restored  if  the  animal  is  placed  in  a 
horizontal  position,  or  if  while  it  is  still  hanging  vertically  the  abdomen 
is  squeezed  or  bandaged.  A  wild  rabbit,  on  the  other  hand,  suffers  no 
inconvenience  from  a  vertical  position ;  it  is  a  more  healthy  animal  in 
every  respect;  its  abdomen  is  not  pendulous,  and  its  vaso-motor 
power  is  intact. 

We  shall,  a  few  pages  later,  be  considering  the  methods  by  which 
blood-pressure  may  be  estimated  in  man.  The  effects  of  gravity  on 
the  pressure  in  various  parts  can  be  well  shown  by  alterations  of 
posture.  This  is  an  important  practical  question,  especially  during 


280 


THE   CIRCULATION    IN   THE   BLOOD-VESSELS  [CH.  XXII. 


FIG.  246.— Effect  of  weak  stimulation  of  the  . 

of  rabbit).    BP,  blood-pressure;  A,  abscissa  or  base-line;  T,  time  in  seconds, 
pressure  and  slow  heart-beats. 


pressure  (carotid 
Note  fall  of  blood- 


T 


FIG.  247.— Effect  of  strong  stimulation  of  the  peripheral  end  of  vagus  on  arterial  blood -pressure  (carot 
of  rabbit).  Note  stoppage  of  heart  and  fall  of  blood-pressure  nearly  to  zero ;  after  the  recommenc 
ment  of  the  heart,  the  blood-pressure  rises,  as  in  fig.  246,  above  the  normal  for  a  short  time. 


CH.  XXII.]  VELOCITY   OF    BLOOD-FLOW  281 

anaesthesia,  when  the  forces  which  counteract  the  bad  effects  of 
gravity  may  not  be  working  efficiently;  if  the  legs  are  hanging 
down,  the  result  may  be  serious. 

The  pressure  in  the  Pulmonary  Circulation  varies  from  J  to  -J 
(mean  J)  of  that  in  the  systemic  vessels. 

The  influence  of  the  Cardiac  Nerves  on  blood-pressure.  The 
importance  of  the  heart's  action  in  the  maintenance  of  blood-pressure 
is  well  shown  by  the  effect  that  stimulation  of  the  vagus  nerve  has 
on  the  blood-pressure  curve.  If  the  vagus  of  an  animal  is  exposed 
and  cut  through,  and  the  peripheral  end  stimulated,  the  result  is  that 
the  heart  is  slowed  or  stopped;  the  arterial  blood-pressure  conse- 
quently falls ;  the  fall  is  especially  sudden  and  great  if  the  heart  is 
completely  stopped.  There  is  a  rise  in  venous  pressure.  The  effect 
on  arterial  pressure  is  shown  in  the  two  accompanying  tracings  ;  fig. 
246  represents  the  effect  of  partial,  and  fig.  247  of  complete  stoppage 
of  the  heart ;  in  both  cases  the  animal  used  was  a  rabbit,  and  the 
artery  the  carotid. 

On  stimulating  the  cardiac  sympathetic  (accelerator  and  augmentor 
fibres)  the  increased  action  of  the  heart  causes  a  rise  of  arterial  pres- 
sure. 

The  effects  of  stimulating  the  central  end  of  the  vagus  and  other 
nerves  cannot  be  understood  until  we  have  studied  the  vaso-motor 
nervous  system. 

The  Velocity  of  the  Blood-flow. 

We  have  already  seen  that  the  velocity  of  the  current  of  blood  is 
inversely  proportional  to  the  sectional  area  of  the  bed  through  which 
it  flows.  The  flow  is  therefore  swiftest  in  the  aorta  and  arteries,  and 
slowest  in  the  capillaries.  In  very  round  numbers,  the  rate  is  about 
a  foot  per  second  in  the  aorta,  and  about  an  inch  per  minute  in  the 
capillaries.  The  capacity  of  the  veins  is  about  twice  or  thrice  that  of 
the  arteries ;  so  the  velocity  in  the  veins  is  from  a  half  to  a  third  of 
that  in  the  corresponding  arteries.  The  rate  in  the  veins  increases  as 
we  approach  the  heart,  as  the  total  sectional  area  of  the  venous  trunks 
becomes  less  and  less. 

The  question  of  velocity  is  one  of  great  importance,  for  it  is  on 
velocity  that  the  actual  amount  of  blood  supplying  the  tissues  mainly 
depends.  In  the  capillaries  the  rate  can  be  measured  by  direct  micro- 
scopic investigation  of  the  transparent  portions  of  animals.  E.  H. 
Weber  and  Valentin  were  among  the  earliest  to  make  these  measure- 
ments in  the  frog,  and  the  mean  of  their  estimates  gives  the  velocity 
as  25  mms.  per  minute  in  the  systemic  capillaries.  In  warm-blooded 
animals  the  velocity  is  somewhat  greater ;  in  the  dog  it  is  -^  to  y^ 
inch  (0'5  to  075  mm.)  per  second.  It  must  be  remembered  that  the 
total  length  of  capillary  vessels  through  which  any  given  portion  of 


282 


THE   CIRCULATION    IN   THE   BLOOD-VESSELS  [CH.  XXII. 


blood  has  to  pass  probably  does  not  exceed  from  -^  to  ^V  inch 
(O'o  mm.),  and  therefore  the  time  required  for  each  quantity  of  blood 
to  traverse  its  own  appointed  portion  of  the  general  capillary  system 
will  scarcely  amount  to  a  second.  It  is  during  this  time  that  the 
blood  does  its  duties  in  reference  to  nutrition. 

In  the  larger  vessels  direct  observations  of  this  kind  are  not 
possible,  and  it  is  necessary  to  have  recourse  to  some  instrumental 
method. 

Volkmann  was  the  first  to  make  more  or  less  accurate  measure- 
ments by  introducing  a  long  (J  -shaped  glass  tube  into  the  course  of 
an  artery.  A  diagram  of  this  hcemodromometer,  as  it  was  termed,  is 
shown  in  the  accompanying  diagram  (fig.  248);  this  is  lilled  with 


FIG.  248.— Volkmann's 
Haemodromom  ter. 


FIG.  249.— Ludwig's 
Stromuhr. 


salt  solution,  and  provided  with  a  stop-cock  a ;  this  tap  is  so  arranged 
that  the  blood  can  flow  straight  across  from  one  section  of  the  artery 
to  the  other ;  then  at  a  given  instant  it  is  turned  into  the  position 
shown  in  the  diagram,  and  the  blood  has  to  traverse  the  long  (J-tube, 
and  the  time  that  it  takes  to  traverse  the  tube,  the  length  of  which 
is  known,  is  accurately  observed.  If  the  sectional  area  of  the  tube  is 
the  same  as  that  of  the  artery,  the  velocity  is  obtained  without 
further  correction;  but  the  difficulty  of  obtaining  glass  tubes  with 
the  exact  calibre  of  every  blood-vessel  which  one  desires  to  experi- 
ment with  led  to  the  abandonment  of  this  method,  and  Ludwig's 
Stromuhr  (literally  stream-clock)  took  its  place.  This  consists  of  a 


CH.  XXII.]  THE   STROMUHR  283 

U-shaped  glass  tube  dilated  at  a  and  a',  the  ends  of  which,  h  and  i, 
are  of  known  calibre.  The  bulbs  can  be  filled  by  a  common  opening 
at  k.  The  instrument  is  so  contrived  that  at  b  and  V,  the  glass  part 
is  firmly  fixed  into  metal  cylinders,  attached  to  a  circular  horizontal 
table  c  c,  capable  of  horizontal  movement  on  a  similar  table  d  d', 
about  the  vertical  axis  marked  in  the  figure  by  a  dotted  line.  The 
openings  in  c  c',  when  the  instrument  is  in  position,  as  in  fig.  249, 
corresponds  exactly  with  those  in  d  d' ;  but  if  c  c'  is  turned  at  right 
angles  to  its  present  position,  there  is  no  communication  between  h 
and  a  and  i  and  a',  but  h  communicates  directly  with  i ;  and  if  turned 
through  two  right  angles  c'  communicates  with  d,  and  c  with  cT,»and 
there  is  no  direct  communication  between  h  and  i.  The  experiment 
is  performed  in  the  following  way : — The  artery  to  be  investigated 
is  divided  and  connected  with  two  cannulse  and  tubes  which  fit  it 
accurately  with  h  and  i\  h  is  the  central  end,  and  i  the  peri- 
pheral ;  the  bulb  a  is  filled  with  olive  oil  up  to  a  point  rather  lower 
than  k,  and  a!  and  the  remainder  of  a  is  filled  with  defibrinated 
blood ;  the  tube  on  k  is  then  carefully  clamped ;  the  tubes  d  and  d' 
are  also  filled  with  defibrinated  blood.  When  everything  is  ready, 
the  blood  is  allowed  to  flow  into  a  through  A,  thus  driving  the  oil 
over  into  a  and  displacing  the  defibrinated  blood  through  i  into  the 
peripheral  end  of  the  artery ;  a'  is  then  full  of  oil ;  when  the  blood 
reaches  the  former  level  of  the  oil  in  a,  the  disc  c  c'  is  turned  rapidly 
through  two  right  angles,  and  the  blood  flowing  through  d  into  a 
again  displaces  the  oil,  which  is  driven  into  a.  This  is  repeated 
several  times,  and  the  duration  of  the  experiment  noted.  The 
capacity  of  a  and  a  is  known;  the  diameter  of  the  artery  is  then 
measured,  and  as  the  number  of  times  a  has  been  filled  in  a  given 
time  is  known,  the  velocity  of  the  current  can  be  calculated. 
We  may  take  an  example  to  illustrate  this : — 

volume  per  second       V 
Velocity  =  -  -    =  -^-. 

sectional  area  b 

If  the  capacity  of  the  bulb  is  5  c.c.,  and  it  required  100  seconds  to 
fill  it  10  times,  then  the  amount  of  blood  passing  through  the  instru- 
ment would  be  50  c.c.  in  100  seconds,  or  0'5  c.c.  in  1  second.  Next, 
suppose  the  diameter  of  the  artery  is  4  mm.  The  sectional  area  is 
Trr2;  r  is  the  radius  (2  mm.),  and  TT  =  3*1416.  From  these  data  we 
get 

V          0-5  c.c.          500  cubic  millimetres 
3lty  =  "a  =  3-1416  x  V  -  3-1416  x  4  8  mm'  Per  sec" 

Many  modifications  of  Ludwig's  original  instrument  have  been 
devised.  Fig.  250  shows  Tigers  ted  t's. 

The  tubes  A  and  B  are  placed  in  connection  with  the  two  ends 


284 


THE  CIRCULATION   IN   THE   BLOOD-VESSELS  [CH.  XXII. 


of  the  cut  artery  as  before ;  there  is  also  a  turntable  arrangement  at 
F,  by  means  of  which  the  two  upper  tubes  C  and  D  may  be  connected 
as  in  the  figure ;  or  by  twisting  it  through  two  right  angles,  D  can  bo 

( ^ made  to  communicate  with  A,  and 

C  with  B.  In  place  of  the  two 
bulbs  of  Ludwig's  instrument 
there  is  a  glass  cylinder  H  which 
contains  a  metal  ball  E.  The 
whole  instrument  is  washed  out 
with  oil  to  delay  clotting,  and 
filled  with  defibrinated  blood.  As 
soon  as  blood  is  allowed  to  flow 
from  the  artery,  the  ball  E  is 
driven  over  by  the  current  till  it 
reaches  the  other  end  of  the 
cylinder;  the  instrument  is  then 
FIG.  250.— Tigerstedt's  stromuhr.  rapidly  rotated  through  two  right 

angles,  and  once  more  the  ball  is 

driven  to  the  opposite  end.  This  is  repeated  several  times,  and  the 
number  of  revolutions  during  a  given  period  is  noted.  The  capacity 
of  the  cylinder  minus  that  of  the  ball  is  ascertained,  and  the  velocity 
is  calculated  by  the  same  formula  as  that  already  given. 

The  Stromuhr  has  one  advantage  over  the  hasmodromometer,  in 
that  it  enables  one  to  note  changes  in  mean  velocity  during  the 
course  of  an  experiment.  The  mean  velocity  varies  very  greatly 
even  during  a  short  experiment.  Thus,  in  the  carotid  artery  of  a 
dog,  the  velocity  of  the  stream  varied  from  350  to  *730  mm.  per 
second  in  the  course  of  eighty  seconds ;  in  the  same  artery  of  the 
rabbit  the  variations  were  still  more  extensive  (94  to  226  mm.  per 
second — Dogiel). 

Other  instruments  have  been  devised  which  give  the  variations  in 
the  velocity  during  the  phases  of  the  heart-beat ;  and  some  of  these 
lend  themselves  to  the  graphic  method,  and  give  tracings  of  what  is 
called  the  velocity  pulse.  Before  we  can  understand  these,  it  is  neces- 
sary first  to  study  the  relationship  of  velocity  to  blood-pressure.  Mere 
records  of  blood-pressure  give  us  no  indication  of  the  velocity  of  the 
blood-stream;  the  latter  depends,  not  on  the  absolute  amount  of 
pressure,  but  on  the  differences  of  pressure  between  successive  points 
of  the  vascular  system.  When  a  fluid  is  in  movement  along  a  tube 
the  forces  maintaining  the  flow  are  two  in  number,  the  one  hydro- 
kinetic,  the  other  hydrostatic.  Thus,  if  we  consider  the  flow  from 
one  point  in  the  tube  to  another  (say,  for  example,  at  1  cm.  dis- 
tance), the  forces  producing  the  flow  are  (1)  the  kinetic  energy  pos- 

9 

by  the  blood  when  it   enters   the  first  spot  (i.e.  -    -  dynes, 


CH   XXII.]  THE   PRESSURE   GRADIENT  285 

or   ^     gramme-centimetres) ;  and  (2)  the  difference  between  the  two 

lateral  pressures  at  the  two  points  in  question.  The  important 
point  to  remember  with  respect  to  the  part  the  pressure  plays,  is 
that  the  actual  value  of  the  lateral  pressure  does  not  matter,  but 
that  the  resulting  velocity,  so  far  as  pressure  is  concerned,  depends 
only  upon  the  fall  of  pressure  between  the  two  points.  Therefore, 
the  measurement  to  be  determined  is  the  rate  of  fall  of  pressure, 
or,  as  it  is  usually  expressed,  the  pressure  gradient.  The  steeper 
this  gradient  is,  the  more  rapid  is  the  flow.  Thus,  if  an  artery 
is  suddenly  cut  across,  the  blood  will  spurt  out  at  a  far  greater 
velocity  than  it  possessed  when  flowing  along  the  intact  artery, 
because  the  pressure  gradient  has  been  enormously  increased  in 
steepness.  If,  on  the  other  hand,  we  suddenly  cut  across  a  vein 
along  which  the  blood  had  been  flowing  at  the  same  pace  as  in  the 
intact  artery  first  investigated,  the  flow  will  not  be  markedly 
accelerated,  because  the  change  in  pressure  gradient  has  not  been 
increased  to  nearly  so  great  an  extent. 

Again,  the  flow  along  a  vein  is  just  as  rapid  as  along  an  artery 
of  the  same  size,  for  although  the  actual  pressure  in  the  vein  is  much 
less,  the  pressure  gradient  is  just  as  steep. 

The  influence  of  the  kinetic  factor  is  also  of  great  importance  in 
the  consideration  of  the  flow  of  blood  along  the  arteries  and  veins. 
In  the  first  place,  it  is  obviously  possible  for  the  blood  to  flow  from 
one  point  to  another  at  a  higher  pressure  if  the  kinetic  energy  at  the 
first  point  is  more  than  enough  to  compensate  for  the  pressure 
increase.  Under  such  circumstances  the  velocity  at  the  second 
point  must  of  course  be  less  than  that  at  the  first.  This  implies, 
therefore,  that  the  bed  of  the  stream  has  widened,  and  under  such 
circumstances  the  blood  could  actually  flow  uphill.  In  the  case  of 
the  veins,  as  we  have  previously  seen,  the  bed  continuously  narrows, 
so  that  this  cannot  take  place ;  still  it  is  possible  to  conceive  such 
a  condition  to  occur  as  that  in  which  the  blood  from  a  well-filled 
vein  empties  into  a  more  collapsed  larger  vein  situated  at  a  higher 
level.  The  one  instance  in  which  this  effect  is  produced,  and  is  of 
great  importance,  is  in  the  filling  of  the  auricles  and  ventricles.  As 
these  cavities  fill,  the  blood  comes  to  rest  and  so  loses  all  kinetic 
energy;  consequently  the  whole  of  the  kinetic  energy  possessed 
by  the  blood  flowing  in  the  veins  is  converted  into  static  energy, 
that  is,  into  a  pressure-head ;  in  this  way  the  cavities  are  distended 
to  a  much  higher  pressure  than  that  in  the  great  veins.  The 
acute  distension  of  the  right  auricle  which  follows  any  sudden 
failure  of  the  right  ventricle  is  brought  about  chiefly  in  this 
way. 

It  is  usual  to  speak  of  the  lateral  pressure  of  the  blood  on  the 


286 


THE   CIRCULATION   IN    THE    BLOOD-VESSELS  [CH.  XXII. 


vessel  wall  as  the  pressure-head,  and  of  the  kinetic  energy  measured 
in  terms  of  a  pressure  as  the  velocity -head.  We  could  then  say  that 
the  velocity  between  any  two  points  is  determined  by  the  difference 
between  the  two  pressure-heads  plus  the  velocity -head  at  the  first 
point.  One  method  of  recording  the  velocity-head  is  by  the  use  of 
a  tube  (Pitot's  tube)  shaped  as  in  the  accompanying  figure  (fig.  251). 
The  blood  is  made  to  enter  at  A,  and  leave  through  B ;  in  the  same 
straight  line  as  A  is  a  tube  C,  and  a  second  tube  D  is  placed  at  right 
angles  to  the  tube  B.  If  the  tubes  C  and  D  are  placed  vertically 
and  were  sufficiently  long,  the  blood  would  flow  up  C  until  it 

reached  a  height  which  would  balance  the 
pressure-head  plus  the  velocity-head ;  in  D 
it  would  only  reach  a  height  sufficient  to 
balance  the  pressure-head;  the  difference 
in  height  between  the  two  would  therefore 
give  the  velocity-head.  As  the  tubes 
would  in  this  way  be  inconveniently  long, 
it  is  better  to  use  short  tubes  connected 
at  the  top  by  glass-  or  rubber-tubing.  The 
air  contained  will  be  compressed,  and  the 
two  pressure-heads  will  balance  one 
another,  so  that  the  difference  in  height 
will  again  represent  the  velocity -head ; 
the  velocity  will  be  directly  proportional 
to  the  square  root  of  this  velocity-head. 
This  is  the  principle  of  one  of  the  best 
instruments  we  possess  for  determining 
velocity,  namely,  Cybulski's  photo-hsemata- 
chometer.  The  meniscus  of  the  fluid  in 
each  tube  is  photographed  on  a  moving 
sensitive  plate,  and  in  this  way  a  graphic 

FIG.    251.— Diagram    to    illustrate  ,     .      r,  ,     .'        n        .    ,,          ,         *         •  i 

the  principle  of  Pitot's  Tube    record  is  obtained  of  the  changes  in  velo- 

cSomCetebri;lski's  Phot°"b8emata'    city  at   times   corresponding   to   different 

parts  of  the  cardiac  cycle.     If  one  wishes 

to  determine  the  velocity  in  absolute  measures,  the  instrument  must 
be  previously  calibrated  by  passing  through  it  fluids  flowing  at  known 
rates.  It  will  be  sufficient  to  give  the  results  of  one  experiment ;  in 
the  carotid  artery  during  the  ventricular  systole  the  flow  was  at  the 
rate  of  238-248  mm.  per  second;  during  the  diastole  it  sank  to 
127-156 ;  in  the  femoral  artery  of  the  same  animal,  these  numbers 
were  356  and  177  respectively. 

To  determine  the  pressure  gradient  in  arteries,  simultaneous 
measurements  of  the  lateral  pressures  in  two  vessels  at  different 
distances  from  the  heart  must  be  recorded. 

It  has  been  found  that  the  diastolic  pressures  in  the  crural  and 


CH.  XXII.] 


C1IAUVEAU  S    DKOMOGRAPH 


287 


carotid  are  practically  identical,  but  that  the  maximum  systolic 
pressure  is  actually  higher  in  the  crural  than  in  the  carotid ;  in  the 
dog  the  difference  may  amount  to  as  much  as  60  mm.  mercury. 
This  difference  is  partly  to  be  explained  in  that  the  carotid  arises 
from  the  aorta  at  a  right  angle,  and  therefore  gives  the  true  pressure- 
liead,  while  the  crural,  to  a  considerable  extent,  faces  the  stream,  and 
therefore  gives  both  pressure-head  and  velocity-head. 

Unfortunately,  at  present  no  really  satisfactory  measurements  are 
at  hand  from  which  the  pressure  gradient  can  be  determined. 

Cybulski's  instrument  is 
not  the  only  one  we  possess 
for  obtaining  records  of  the 
velocity-pulse.  Vierordt  in- 
vented a  haemo  -  tachometer, 
employing  the  principle  of  the 
hydrometric  pendulum ;  his 
instrument  was  improved  by 
Chauveau.  Chauveau's  in- 
strument is  shown  in  fig.  252. 

It  consists  of  a  thin  brass  tube,  a, 
in  one  side  of  which  is  a  small  per- 
foration closed  by  thin  vulcanised 
india-rubber.  Passing  through  the 
rubber  is  a  fine  lever,  one  end  of 
which,  slightly  flattened,  extends 
into  the  lumen  of  the  tube,  while 
the  other  moves  over  the  face  of  a 
dial.  The  tube  is  inserted  into  the 
interior  of  an  artery,  and  ligatures 

applied  to  fix  it,  so  that  the  "velocity  pulse,"  i.e.,  the  change  of  velocity  with  each 
heart-beat,  may  be  indicated  by  the  movement  of  the  outer  extremity  of  the  lever 
on  the  face  of  the  dial. 

In  order  to  obtain  the  actual  value  of  these  movements  in  terms 
of  velocity,  the  instrument  must  be  calibrated  beforehand.  The  next 
diagram,  fig.  253,  shows  how  the  instrument  may  be  adapted  to  give 


FIG.  252.— Diagram  of  Chauveau's  Dromograph.  a,  Brass 
tube  for  introduction  into  the  lumen  of  the  artery, 
and  containing  an  index  needle,  which  passes 
through  the  elastic  membrane  in  its  side,  and 
moves  by  the  impulse  of  the  blood  -  current ; 
c,  graduated  scale,  for  measuring  the  extent  of  the 
oscillations  of  the  needle. 


FIG.  253.— Chauveau's  Dromograph  connected  with  tambours  to  give  a  graphic  record. 

a  graphic  record.     The  movements  of  the  pendulum  are  brought  to 
bear  upon  a  tambour,  B,  which  communicates  by  a  tube  with  the 


288 


THE   CIRCULATION    IN   THE    BLOOD-VESSELS  [CH.  XXII. 


recording  tambour  C.  If  the  mass  of  the  pendulum  is  small,  the 
accuracy  of  the  instrument  is  considerable.  Fig.  254  shows  the 
tracing  obtained  from  the  carotid  artery  of  the  horse.  The  pressure 
curve  is  placed  below  it  for  purpose  of  comparison.  The  tracing 
shows  the  effects  during  the  time  corresponding  to  one  cardiac  cycle. 
On  both  curves  the  upstroke  is  the  effect  of  the  ventricular  systole ; 
this  terminates  at  the  apex  of  the  first  small  curve  (between  the 
vertical  lines  3  and  4)  on  the  down  stroke  of  the  pressure  curve,  the 
rest  of  the  downstroke  until  the  commencement  of  the  next  systole 
(line  5)  corresponds  with  the  ventricular  diastole.  Beyond  the  line  4 
is  a  larger  secondary  wave,  which  is  known  as  the  dicrotic  wave ;  the 
smaller  post-dicrotic  waves  are  due  to  elastic  vibrations.  We  shall 
be  studying  all  these  points  more  in  detail  when  we  come  to  the 
pulse.  When  we  compare  the  two  curves  together  we  note  that  the 
velocity  curve  reaches  its  maximum  before  the  pressure  curve ;  this 


FIG.  254.— Velocity  curve  (V),  and  pressure  curve  (P)  from  the  carotid  artery  of  the  horse ;  oo,  abscissa 
of  velocity  curve;  1,  2,  3,  4  show  simultaneous  points  on  both  curves.    (Chauveau  and  Marey.) 

is  because,  as  the  arteries  become  overfilled,  the  heart  cannot  maintain 
the  initial  velocity  of  output.  The  blood  is  thus  forced  along  the 
arteries ;  then  comes  the  diastole,  and  the  recoil  of  the  elastic  arteries 
not  only  forces  the  blood  onwards,  but  also  produces  a  back-swing 
against  the  closed  aortic  valves ;  this  produces  the  notch  before  the 
dicrotic  wave;  the  blood  is  reflected  from  the  aortic  valves,  once 
more  producing  a  positive  wave  (the  dicrotic  wave).  This  affects 
both  speed  and  pressure.  It  will  be  noticed  that  during  the  dicrotic 
notch  the  pressure  falls  comparatively  little,  but  in  the  velocity  curve 
the  fall  is  considerable,  and  the  curve  may  sink  below  the  base  line  oo. 
This  negative  effect  is  naturally  much  more  marked  in  the  aorta  and 
its  first  large  branches  than  in  situations  farther  from  the  heart. 

In  actual  values  Chauveau  found  that  the  velocity  in  the  horse's 
carotid  reached  520  mm.  per  second  during  systole ;  it  sank  to  220 
at  the  time  of  the  dicrotic  wave,  and  to  150  during  diastole. 

The  effect  on  the  blood-flow  of  functional  activity  or  vaso-motor 


CH.  XXII.]  TIME  OF   A   COMPLETE   CIRCULATION  289 

changes  has  also  been  observed.  Thus  Lortet  found  that  the  carotid 
flow  is  five  or  six  times  greater  when  the  horse  is  actively  masticating 
than  when  it  is  at  rest.  After  section  of  the  cervical  sympathetic, 
the  lessening  of  the  peripheral  resistance  raised  the  velocity  from 
540  to  750  mm.  per  second. 

The  Time  of  a  Complete  Circulation. 

Among  the  earliest  investigators  of  the  question  how  long  an 
entire  circulation  takes,  was  Hering.  He  injected  a  solution  of 
potassium  ferrocyanide  into  the  central  end  of  a  divided  jugular 
vein,  and  collected  the  blood  either  from  the  other  end  of  the  same 
vein,  or  from  the  corresponding  vein  of  the  other  side.  The  sub- 
stance injected  is  one  that  can  be  readily  detected  by  a  chemical 
test  (the  prussian  blue  reaction).  Vierordt  improved  this  method 
by  collecting  the  blood  as  it  flowed  out,  in  a  rotating  disc  divided  into 
a  number  of  compartments.  The  blood  was  tested  in  each  compart- 
ment, and  the  ferrocyanide  was  discovered  in  one  which  in  the  case  of 
the  horse  received  the  blood  about  half  a  minute  after  the  injection 
had  been  made.  The  experiment  was  performed  in  a  large  number 
of  animals,  and  the  following  were  a  few  of  the  results  obtained : — 

In  the  horse  .  .  .  .31  seconds. 

„       dog  .  .  .         16        „ 

„       cat  .  .  .  6-5     „ 

fowl  .  .  .  5 

At  first  sight  these  numbers  show  no  agreement,  but  in  each  case 
it  was  found  that  the  time  occupied  was  27  heart-beats.  The  dog's 
heart,  for  instance,  beats  twice  as  fast  as  the  horse's,  and  so  the  time 
of  the  entire  circulation  only  occupies  half  as  much  time. 

The  question  has  recently  been  reinvestigated  by  Stewart  by 
improved  methods,  which  have  shown  that  the  circulation  time  is 
considerably  less  than  was  found  by  the  researches  of  Hering  and 
Vierordt.  The  great  objection  to  the  older  method  is  the  fact  that 
haemorrhage  is  occurring  throughout  the  experiment,  and  this  would 
materially  weaken  the  heart  and  slow  down  the  circulation.  Stewart 
has  employed  two  methods.  In  the  first,  the  carotid  artery  is  exposed, 
and  non-polarisable  electrodes  applied  to  it.  These  are  placed  in 
circuit  with  a  cell,  a  galvanometer,  and  one  arm  of  a  Wheatstone's 
bridge.  After  the  resistances  in  the  bridge  have  been  balanced,  and 
the  galvanometer  needle  brought  to  rest,  a  small  quantity  of  strong 
sodium  chloride  solution  is  injected  into  the  opposite  carotid.  As 
soon  as  the  salt  reaches  the  carotid  artery,  the  resistance  of  the 
blood  is  altered,  the  balance  of  the  Wheatstone's  bridge  is  upset,  and 
the  galvanometer  needle  moves.  The  period  between  the  injection 
and  the  swing  of  the  needle  is  accurately  noted. 

T 


290  THE   CIRCULATION   IN   THE   BLOOD-VESSELS  [CH.  XXII. 

The  second  method  used  is  even  simpler,  and  gives  practically  the 
same  results;  a  solution  of  methylene  blue  is  injected  into  a 
vessel.  The  corresponding  vessel  on  the  opposite  side  is  exposed, 
placed  upon  a  sheet  of  white  paper,  and  strongly  illuminated.  The 
time  is  noted  between  the  injection  and  the  moment  when  the  blue 
colour  is  seen  to  appear  in  the  vessel  under  observation.  Stewart 
has  applied  these  methods  also  for  determining  the  time  occupied 
by  the  passage  of  blood  through  various  districts  of  the  circulation ; 
the  longest  circulation  times  were  found  in  the  portal  system  and 
the  lower  limbs.  He  calculates  that  the  total  circulation  time  in 
man  is  about  15  seconds. 

None  of  these  methods,  however,  give  the  true  time  of  the  entire 
circulation ;  they  give  merely  the  shortest  possible  time  in  which  any 
particle  of  blood  can  travel  through  the  shortest  pathway.  The 
blood  that  travels  in  the  axial  current,  or  which  takes  a  broad  path- 
way through  wide  capillaries,  will  arrive  far  more  speedily  at  its 
destination  than  that  which  creeps  through  tortuous  or  constricted 
vessels.  The  direct  observations  of  Tigers  ted  t  on  the  output  of  the 
left  ventricle  show  that  the  circulation  time  of  the  whole  blood  is  at 
least  three  times  as  long  as  the  period  arrived  at  by  the  Hering 
method.  It  is  therefore  fallacious  to  use  the  circulation  times 
arrived  at  by  Hering's  or  Stewart's  methods  as  a  basis  for  calculating 
the  total  amount  of  the  blood  in  the  body. 

The  Pulse. 

This  is  the  most  characteristic  feature  of  the  arterial  flow.  It  is 
the  response  of  the  arterial  wall  to  the  changes  in  lateral  pressure 
caused  by  each  heart-beat. 

A  physician  usually  feels  the  pulse  in  the  radial  artery,  since  this 
is  near  the  surface,  and  supported  by  bone.  It  is  a  most  valuable 
indication  of  the  condition  of  the  patient's  heart  and  vessels.  It  is 
necessary  in  feeling  a  pulse  to  note  the  following  points : — 

1.  Its  frequency ;  that  is  the  number  of  pulse-beats  per  minute. 

This  gives  the  rate  of  the  heart-beats. 

2.  Its  strength ;  whether  it  is  a  strong,  bounding  pulse,  or  a  feeble 

beat;    this    indicates   the   force   with   which   the   heart   is 
beating. 

3.  Its  regularity  or  irregularity ;  irregularity  may  occur  owing  to 

irregular  cardiac  action  either  in  force  or  in  rhythm. 

4.  Its  tension ;  that  is  the  force  necessary  to  obliterate  it.     This 

gives  an  indication  of  the  state  of  the  arterial  walls  and  the 
peripheral  resistance. 

In  disease  there  are  certain  variations  in  the  pulse,  of  which  we 
shall  mention  only  two ;  namely,  the  intermittent  pulse,  due  to  the 


CH.  XXII.] 


THE   PULSE 


291 


heart  missing  a  beat  every  now  and  then;  and  the  water-hammer 
pulse,  due  either  to  aortic  regurgitation  or  to  a  loss  of  elasticity  of 
the  arterial  walls;  either  of  these  circumstances  diminishes  the 


FIG.  255. — Marey's  Sphygmograph,  modified  by  Mahomed. 

onward  flow  of  blood  during  the  heart's  diastole,  and  thus  the  sudden- 
ness of  the  impact  of  the  blood  on  the  arterial  wall  during  systole  is 
increased.  When  this  condition  is  due  to  arterial  disease,  such  as 
atheroma  or  calcification,  this  sudden  pulse,  combined  with  the 
decreased  extensibility  of  the  arteries,  may  lead  to  rupture  of  the 
walls,  and  this  is  especially  serious  if  it  occurs  in  the  arteries  of  the 
brain  (one  cause  of  apoplexy). 

In  order  to  study  the  pulse  more  fully,  it  is  necessary  to  obtain 


FIG.  256.—  Diagram  of  the  lever  of  the  Sphygmograph. 

a  graphic  record  of  the  pulse-beat,  and  this  is  accomplished  by  the 
use  of  an  instrument  called  the  Sphygmograph.  This  instrument 
consists  of  a  series  of  levers,  at  one  end  of  which  is  a  button  placed 
over  the  artery ;  the  other  end  is  provided  with  a  writing-point  to 


292 


THE  CIRCULATION   IN   THE   BLOOD-VESSELS  [oil.  XXII. 


inscribe  the  magnified  record  of  the  arterial  movement  on  a  travelling 
surface. 

The  instruments  most  frequently  used  are  those  of  Marey,  one  of 
the  numerous  modifications  of  which  is  represented  in  figures  255, 
256,  and  257,  and  of  Dudgeon  (fig.  258). 


FIG.  257.— The  Sphygmograph  applied  to  the  arm 


Each  instrument  is  provided  with  an  arrangement  by  which  the 
pressure  can  be  adjusted  so  as  to  obtain  the  best  record.  The 
measurement  of  the  pressure  is,  however,  rough,  and  both  instruments 
have  the  disadvantage  of  giving  oscillations  of  their  own  to  the 


FIG.  258.— Dudgeon's  Sphygmograph.    The  dotted  outline  represents  the  piece  of  blackened  paper  on 
which  the  sphygmogram  is  written. 

sphygmogram;  this  is  specially  noticeable  in  Dudgeon's  Sphygmo- 
graph. But  these  defects  may  be  overcome  by  the  use  of  some 
form  of  sphygmometer.  (See  later,  p.  295.)  It  is  also  important 
to  remember  that  the  pad  or  button  placed  upon  the  artery  rests 
partly  on  the  venae  comites,  so  that  not  only  arterial  tension  but  any 


CH.  XXII.] 


SPHYGMOGRAMS 


293 


turgidity  arising  from  venous  congestion,  will  affect  the  height  and 
form  of  the  sphygmographic  record. 

Fig.  259  represents  a  typical  sphygmographic  tracing  obtained 


from  the  radial  artery.  It  consists 
expansion  of  the  artery,  and  a  down- 
stroke  due  to  its  retraction.  The 
descent  is  more  gradual  than  the 
upstroke,  because  the  elastic  recoil 
acts  more  constantly  and  steadily 
than  the  heart-beat.  On  the  descent 
are  several  secondary  (katacrotic) 
elevations. 

A  is  the  primary,  or  percussion 
wave ;  C  is  the  pre-dicrotic,  or  tidal 
wave ;  D  is  the  dicrotic  wave,  and  E 


of   an   upstroke   due    to   the 


FIG.  259. — Diagram  of  pulse-tracing.  A,  up- 
stroke; B,  downstroke ;  C,  pre-dicrotic 
wave;  D,  dicrotic;  E,post-dicrotic  wave. 


the  post-dicrotic  wave,  and   of   these 

there  may  be  several.     In  some  rare 

cases  there  is  a  secondary  wave  on  the  upstroke,  which  is  called  an 

anacrotic  wave  (fig.  260). 

These  various  secondary  waves  have  received  different  inter- 
pretations, but  the  best  way  of  explaining  them  is  derived  from 
information  obtained  by  taking  simultaneous  tracings  of  the  pulse, 
aortic  pressure,  apex  beat,  and  intraventricular  pressure,  as  in  the 
researches  of  Hiirthle.  By  this  means  it  is  found  that  the  percussion 
and  tidal  waves  occur  during  the  systole  of  the  heart,  and  the  other 
waves  during  the  diastole.  The  closure  of  the  aortic  valves  occurs 
just  before  the  dicrotic  wave.  The  secondary  waves  on  the  down- 
stroke  other  than  the  dicrotic  are  due  to  the  elastic  tension  of  the 


FIG.  260. — Anacrotic  pulse. 

arteries,  and  are  increased  in  number  when  the  tension  of  the  arteries 
is  greatest.  Some  of  the  post-dicrotic  waves  are  also  doubtless 
instrumental  in  origin.  The  dicrotic  wave  has  a  different  origin.  It 
was  at  one  time  thought  that  this  wave  was  due  to  a  wave  of  pressure 
reflected  from  the  periphery,  but  this  view  is  at  once  excluded  by  the 
fact  that  wherever  we  take  the  pulse-tracing,  whether  from  the  aorta, 
carotid,  radial,  dorsalis  pedis,  or  elsewhere,  this  secondary  elevation 
always  follows  the  percussion  wave  after  the  same  interval,  showing 
that  it  has  its  origin  in  the  commencement  of  the  arterial  system. 


294  THE   CIRCULATION   IN   THE   BLOOD-VESSELS  [dl.  XXII. 

Moreover,  a  single  pressure-wave  reflected  from  the  periphery  would 
be  impossible,  as  such  a  wave  reflected  from  one  part  would  be  inter- 
fered with  by  those  from  other  parts ;  moreover,  a  dicrotic  elevation 
produced  by  a  pressure-wave  reflected  from  the  periphery,  would  be 
increased  by  high  peripheral  resistance,  and  not  diminished,  as  is 
actually  the  case. 

The  primary  cause  of  the  dicrotic  wave  is  the  closure  of  the  semi- 
lunar  valves;  as  already  explained  when  we  were  considering  the 

velocity  pulse  (p.  288),  the  inflow 
of  blood  into  the  aorta  suddenly 
ceases,  and  the  blood  is  driven  back 
against  the  closed  aortic  doors  by 
the  elastic  recoil  of  the  aorta;  tha 
FIG.  26i.— Dicrotic  pulse  wave  rebounds  f  rom  these  and  is 

propagated     through    the     arterial 

system  as  the  dicrotic  elevation.  The  production  of  the  dicrotic 
wave  is  favoured  by  a  low  blood-pressure  when  the  heart  is  beating 
forcibly,  as  in  fever.  Such  a  pulse  is  called  a  dicrotic  pulse  (fig.  261), 
and  the  second  beat  can  be  easily  felt  by  the  finger  on  the  radial 
artery. 

The  percussion  wave  is  produced  by  the  ventricular  systole 
expanding  the  artery.  The  sharp  top  at  its  summit  is  due  to  the 
sudden  upward  spring  of  the  light  lever  of  the 
sphygmograph.  If  it  were  possible  to  obtain  a 
true  record  of  what  really  occurs,  we  should 
doubtless  have  a  tracing  as  shown  by  the  con- 
tinuous line  in  the  accompanying  figure  (fig.  259). 
The  apex  of  the  tidal  wave,  B,  marks  the  end  of 
the  ventricular  systole. 

In  our  study  of  intracardiac  pressure,  we 
saw  that  the  systolic  plateau  sometimes  has  an 
ascending,  sometimes  a  descending,  slope  (see  dicrotic  waves. 
p.  243) ;  we  now  come  to  the  explanation  of  this 
fact.  If  after  the  first  sudden  rise  of  pressure  in  the  aorta  the  peri- 
pheral resistance  is  low,  and  the  blood  can  be  driven  on  from  the 
aorta  more  rapidly  than  it  is  thrown  in,  the  plateau  will  sink.  If, 
on  the  other  hand,  the  peripheral  resistance  is  high,  the  aortic 
pressure  will  rise  as  long  as  the  blood  is  flowing  in,  and  we  get  an 
ascending  systolic  plateau  and  an  anacrotic  pulse.  Thus  an  anacrotic 
pulse  is  seen  in  Blight's  disease,  where  the  peripheral  resistance  is 
very  high. 

If  a  long  pulse-tracing  is  taken,  the  effect  of  the  respiration  can 
be  seen  causing  an  increase  of  pressure,  and  a  slight  acceleration  of 
the  heart's  beats  during  inspiration. 

The  main  waves  of  the  pulse  can  be  demonstrated  without  the 


OIL  XXII.] 


BLOOD-PRESSURE   IN   MAN 


295 


FIG.   263.— Hsemauto 
to  be  read 
m  right  to  left. 


use  of  any  instrument  at  all,  by  allowing  the  blood  to  spurt  from  a 
cut  artery  on  to  the  surface  of  a  large  sheet  of  white  paper  travel- 
ling past  it.  We  thus  obtain  what  is  very  appropriately  called  a 
hcemautograph  (fig.  263). 

A  distinction  must  be  drawn  between  the  pulse 
as  felt  at  any  one  spot  in  the  course  of  an  artery, 
and  the  pulse-wave  which  is  propagated  through- 
out the  arterial  system.  This  wave  of  expansion 
travels  along  the  arteries,  and  is  started  by  the  pro- 
pulsion of  the  contents  of  the  left  ventricle  into  the 
already  full  arterial  system.  The  more  distant  the 
artery  from  the  heart,  the  longer  the  interval  that 
elapses  between  the  ventricular  beat  and  the  arrival 
of  the  pulse-wave.  Thus  it  is  felt  in  the  carotid 
earlier  than  in  the  radial  artery,  and  is  still  later 
in  the  dorsal  artery  of  the  foot.  The  difference 
of  time  is,  however,  very  slight;  it  is  only  a  small 
fraction  of  a  second;  the  wave  travels  at  the  rate  of 
from  5  to  10  metres  a  second,  that  is  twenty  to 
thirty  times  the  rate  of  the  blood  current. 

The  Rate  of  Propagation  of  the  Pulse-Wave. — The  method  of  ascertaining  this 
may  be  illustrated  by  the  use  of  a  long  elastic  tube  into  which  fluid  is  forced  by 
the  sudden  stroke  of  a  pump.  If  a  series  of  levers  are  placed  along  the  tube  at 
measured  distances,  those  nearest  the  pump  will  rise  first,  those  farthest  from  it 
last.  If  these  are  arranged  to  write  on  a  revolving  cylinder  under  one  another, 
this  will  be  shown  graphically,  and  the  time-interval  between  their  movements 
can  be  measured  by  a  time-tracing.  The  same  principle  is  applied  to  the  arteries 
of  the  body;  a  series  of  Marey's  tambours  are  applied  to  the  heart  and  to 
various  arteries  at  known  distances  from  the  heart ;  their  levers  are  arranged  to 
write  immediately  under  one  another,  as  in  fig.  220,  p.  241.  The  difference  in  time 
between  the  commencement  of  their  upstrokes  is  measured  by  a  time-tracing  in 
the  usual  way. 

The  tracing  taken  with  a  sphygmograph  is  that  of  the  pressure 
pulse ;  we  may  regard  it  as  a  blood-pressure  tracing  without  a  base 
line.  The  actual  measurement  of  the  blood-pressure  in  the  human 
subject  is  effected  by  instruments  which  may  be  applied  to  the  vessels 
without  any  dissection. 

These  instruments  are  termed  sphygmometers,  and  the  best  of 
them  are  modifications  of  one  originally  introduced  by  Eiva  Eocci. 
C.  J.  Martin's  pattern  consists  of  a  four-sided  elastic  bag  about  four 
and  a  half  inches  wide,  and  long  enough  to  encircle  the  arm.  It  is 
wrapped  round  the  arm,  and  outside  of  it  a  cuff  of  strong  canvas  is 
firmly  strapped.  Air  is  forced  into  the  bag  by  a  tube  leading  from 
a  ball  syringe;  this  tube  is  also  connected  by  a  side  branch  to  a 
mercury  manometer.  As  one  continues  to  pump  and  distend  the 
bag,  the  pulse-beats  are  transmitted  to  the  mercury  which  is  seen  to 
rise  in  the  manometer  and  oscillate  with  the  pulse-beats.  As  the 


296 


THE   CIRCULATION   IN  THE   BLOOD-VESSELS  [CH.  XXII. 


pressure  rises  the  oscillations  become  more  pronounced,  and  at  a 
certain  point  they  exhibit  a  greater  excursion  than  they  do  at  any 
other  height ;  beyond  this  point  of  maximal  pulsation,  the  oscilla- 
tions diminish  in  amplitude,  and  as  the  distension  of  the  bag  is 
increased  still  more,  the  pressure  is  at  last  reached,  when  it  is 
sufficient  to  obliterate  the  pulse,  and  the  oscillations  of  the  mercurial 
column  cease,  and  the  pulse  is  no  longer  to  be  felt  at  the  wrist.  The 
pressure  necessary  to  do  this  is  equal  to  the  systolic  pressure,  and  the 
height  of  the  mercurial  column  should  be  noted  when  the  pulse  just 
disappears.  The  point  of  maximal  pulsation  gives  a  reading  of  the 


FIG.  264.— Martin's  Sphygmometer  (made  by  Hawskley,  357  Oxford  Street). 

diastolic  pressure.  The  systolic  pressure  is  more  easily  read  than  the 
diastolic  pressure,  for  it  is  by  no  means  easy  to  judge  accurately 
where  the  pulsations  are  greatest.  Moreover,  the  amount  of  systolic 
pressure  gives  one  more  useful  information  of  the  condition  of  the 
circulation  than  does  the  diastolic  pressure. 

The  normal  pressure  in  the  radial  artery  of  healthy  young  adults 
is  110  to  120  mm.  Hg.  It  appears  to  be  as  constant  as  the  body 
temperature.  In  the  recumbent  posture  the  pressure  is  slightly 
lower  than  in  the  erect  position.  This  relation  is  reversed  in  condi- 
tions of  exhaustion.  The  pressure  in  the  lower  limbs  is  greater  than 
that  in  the  upper  limbs  in  the  standing  posture  owing  to  the  effect 
of  gravity.  During  muscular  exertion  the  pressure  is  raised,  while 
in  the  subsequent  period  of  rest  it  is  subnormal.  Mental  work 
raises  the  pressure ;  during  rest  and  sleep  it  is  lowered.  The  taking 


CH.  XXII.]  THE   CAPILLARY  FLOW  297 

of  food  produces  no  noteworthy  effect.     In  disease  there  are  naturally 
great  variations,  and  the  study  of  these  has  yielded  valuable  results. 

The  Capillary  Plow. 

When  the  capillary  circulation  is  examined  in  any  transparent 
part  of  a  living  animal  by  means  of  the  microscope  the  blood  is  seen 
to  flow  with  a  constant  equable  motion;  the  red  blood-corpuscles 
move  along,  mostly  in  single  file,  and  bend  in  various  ways  to 
accommodate  themselves  to  the  tortuous  course  of  the  capillary,  but 
instantly  recover  their  normal  outline  on  reaching  a  wider  vessel. 

At  the  circumference  of  the  stream  in  the  larger  capillaries,  and 
in  the  small  arteries  and  veins,  there  is  a  layer  of  blood-plasma 
in  contact  with  the  walls  of  the  vessel,  which  moves  more 
slowly  than  the  blood  in  the  centre.  Anyone  who  has 
rowed  on  a  river  will  know  that  the  swiftest  current  is  in  the 
middle  of  the  stream.  The  red  corpuscles  occupy  the  middle  of  the 
stream  and  move  with  comparative  rapidity ;  the  colourless  corpuscles 
run  much  more  slowly  by  the  walls  of  the  vessel ;  while  next  to  the 
wall  there  is  a  transparent  space  in  which  the  fluid  is  at  comparative 
rest  (the  so-called  "  still  layer  ") ;  if  any  of  the  corpuscles  happen  to 
be  forced  within  it,  they  move  more  slowly  than  before,  rolling  lazily 
along  the  side  of  the  vessel,  and  often  adhering  to  its  wall.  Some- 
times, when  the  motion  of  the  blood  is  not  strong,  many  of  the  white 
corpuscles  collect  in  a  capillary  vessel,  and  for  a  time  entirely  prevent 
the  passage  of  the  red  corpuscles. 

When  the  peripheral  resistance  is  greatly  diminished  by  the 
dilatation  of  the  small  arteries,  so  much  blood  passes  on  from  the 
arteries  into  the  capillaries  at  each  stroke  of  the  heart,  that  there  is 
not  sufficient  remaining  in  the  arteries  to  distend  them.  Thus,  the 
intermittent  current  of  the  ventricular  systole  is  not  converted  into 
a  continuous  stream  by  the  elasticity  of  the  arteries  before  the  capil- 
laries are  reached ;  and  so  intermittency  of  the  flow  occurs  both  in 
capillaries  and  veins,  and  a  pulse  is  produced  there.  The  same  pheno- 
menon may  occur  when  the  arteries  become  rigid  from  disease,  and 
when  the  beat  of  the  heart  is  so  slow  or  so  feeble  that  the  blood  at 
each  cardiac  systole  has  time  to  pass  on  to  the  capillaries  before  the 
next  stroke  occurs ;  the  amount  of  blood  sent  out  at  each  stroke  is 
then  insufficient  to  properly  distend  the  elastic  arteries. 

It  was  formerly  supposed  that  the  occurrence  of  any  transudation 
from  the  interior  of  the  capillaries  into  the  midst  of  the  surrounding 
tissues  was  confined,  in  the  absence  of  injury,  strictly  to  the  fluid 
part  of  the  blood;  in  other  words,  that  the  corpuscles  could  not 
escape  from  the  circulating  stream,  unless  the  wall  of  the  containing 
blood-vessel  was  ruptured.  Augustus  Waller  affirmed,  in  1846,  that 


298 


THE   CIRCULATION   IN   THE   BLOOD-VESSELS  [CH.  XXII. 


he  had  seen  blood-corpuscles,  both  red  and  white,  pass  bodily  through 
the  wall  of  the  capillary  vessel  in  which  they  were  contained ;  and 
that,  as  no  opening  could  be  seen  before  their  escape,  so  none  could 
be  observed  afterwards — so  rapidly  was  the  part  healed.  But  these 
observations  did  not  attract  much  notice  until  the  phenomenon  was 
rediscovered  by  Cohnheim  in  1867. 

Cohnheim's  experiment  was  performed  in  the  following  manner : 
A  frog  is  anaesthetised ;  and  the  abdomen  having  been  opened,  a  portion 
of  small  intestine  is  drawn  out,  and  its  transparent  mesentery  spread 
out  under  a  microscope.  After  a  variable  time,  occupied  by  dilatation, 
following  contraction  of  the  minute  vessels  and  accompanying 
quickening  of  the  blood-stream,  there  ensues  a 
retardation  of  the  current,  and  blood-corpuscles 
begin  to  make  their  way  through  the  capillaries 
and  small  vessels. 

Diapedesis,  or  emigration  of  the  white  cor- 
puscles, occurs  to  a  small  extent  in  health. 
But  it  is  much  increased  in  inflammation,  and 
may  go  on  so  as  to  form  a  large  collection  of 
leucocytes  (i.e.  white  corpuscles)  outside  the 
vessels. 

The  emigration  of  red  corpuscles  is  only 
seen  in  inflammation,  and  is  a  passive  process ; 
it  occurs  when  the  holes  made  by  the  emigrat- 
ing leucocytes  do  not  close  up  immediately, 
and  so  the  red  corpuscles  escape  too. 

The  real  meaning  of  the  process  of  inflam- 
mation is  a  subject  which  is  being  much  dis- 
cussed now,  but  it  may  be  interesting  to  state 
briefly  the  views  of  Metschnikoff,  who  has  in 
recent  years  been  a  prominent  investigator  of 
the  subject.  Even  if  these  views  do  not  repre- 
sent the  whole  truth,  it  can  hardly  be  doubted 
that  the  phenomena  described  play  a  very 
important  part  in  the  process.  Metschnikoff  teaches  that  the 
vascular  phenomena  of  inflammation  have  for  their  object  an  in- 
crease in  the  emigration  of  leucocytes,  which  have  the  power  of 
devouring  the  irritant  substance,  and  removing  the  tissues  killed  by 
the  lesion.  They  are  therefore  called  phagocytes  (devouring  or 
scavenging  corpuscles).  It  may  be  that  the  microbic  influence,  or 
the  influence  of  the  chemical  poisons  they  produce,  is  too  powerful 
for  the  leucocytes;  then  they  are  destroyed,  and  the  dead  leuco- 
cytes become  pus  corpuscles;  but  if  the  leucocytes  are  successful 
in  destroying  the  foreign  body,  micro-organisms,  and  disintegrated 
tissues,  they  disappear,  wandering  back  to  the  blood-vessels,  and 


FIG.  265.— A  large  capillary 
from  the  frog's  mesentery 
eight  hours  after  irrita- 
tion had  been  set  up, 
showing  emigration  of 
leucocytes,  a,  Cells  in 
the  act  of  traversing  the 
capillary  wall;  &,  some 
already  escaped.  (Frey.) 


CH.  XXII.]  THE  VENOUS   FLOW  299 

the  lost  tissue  is  replaced   by  a  regeneration    of   the  surrounding 
tissues.* 

The  circulation  through  the  capillaries  must,  of  necessity,  be 
largely  influenced  by  that  which  occurs  in  the  vessels  on  either  side 
of  them  in  the  arteries  or  the  veins;  their  intermediate  position 
causes  them  to  feel  at  once  any  alteration  in  the  size,  rate,  or  pres- 
sure of  the  arterial,  and  more  especially  of  the  venous  blood-stream. 
The  apparent  contraction  of  the  capillaries,  on  the  application  of 
certain  irritating  substances,  and  during  fear,  and  their  dilatation  in 
blushing,  may  be  referred  primarily  to  the  action  of  the  small  arteries. 

The  Venous  Plow. 

The  blood-current  in  the  veins  is  maintained  primarily  by  the 
vis  a  tergo,  that  is,  the  force  behind,  which  is  the  blood-pressure 
transmitted  from  the  heart  and  arteries ;  but  very  effectual  assist- 
ance to  the  flow  is  afforded  by  the  action  of  the  muscles  capable  of 
pressing  on  the  veins  with  valves,  as  well  as  by  the  suction  action 
of  the  heart,  and  the  aspiratory  action  of  the  thorax  (vis  a 
fronte). 

The  effect  of  muscular  pressure  upon  the  circulation  may  be  thus 
explained.  When  pressure  is  applied  to  any  part  of  a  vein  and  the 
current  of  blood  in  it  is  obstructed,  the  portion  behind  the  seat  of 
pressure  becomes  swollen  and  distended  as  far  back  as  the  next  pair 
of  valves,  which  are  in  consequence  closed  (fig.  202,  B,  p.  220).  Thus, 
whatever  force  is  exercised  by  the  pressure  of  the  muscles  on  the 
veins,  is  distributed  partly  in  pressing  the  blood  onwards  in  the 
proper  course  of  the  circulation,  and  partly  in  pressing  it  backwards 
and  closing  the  valves  behind. 

The  circulation  might  lose  as  much  as  it  gains  by  such  an  action, 
if  it  were  not  for  the  numerous  communications  which  the  veins  make 
with  one  another ;  through  these,  the  closing  up  of  the  venous 
channel  by  the  backward  pressure  is  prevented  from  being  any  serious 
hindrance  to  the  circulation,  since  the  blood,  the  onward  course  of 
which  is  arrested  by  the  closed  valves,  can  at  once  pass  through 
some  anastomosing  channel,  and  proceed  on  its  way  by  another 
vein.  Thus,  the  effect  of  muscular  pressure  upon  veins  which  have 
valves,  is  turned  almost  entirely  to  the  advantage  'of  the  circula- 
tion. 

In  the  web  of  the  bat's  wing,  the  veins  are  furnished  with  valves, 
and  possess  the  remarkable  property  of  rhythmical  contraction  and 
dilatation,  whereby  the  current  of  blood  within  them  is  distinctly 
accelerated  (Wharton  Jones).  The  contraction  occurs,  on  an  average, 

*  This  question  is  closely  related  to  that  of  immunity,  which  is  discussed  in  the 
chapter  on  the  Blood  (Chapter  XXIX.). 


300  THE   CIRCULATION   IN   THE   BLOOD-VESSELS  [CH.  XXII. 

about  ten  times  in  a  minute ;  the  existence  of  valves  prevents  regur- 
gitation,  so  the  entire  effect  of  the  contractions  is  auxiliary  to  the 
onward  current  of  blood.  Analogous  phenomena  are  occasionally 
found  in  other  animals. 

A  venous  pulse  is  observed  under  the  conditions  previously 
described  (p.  297),  when  the  arterioles  are  dilated  so  that  the  arterial 
pulse  passes  through  the  capillaries  to  the  veins. 

A  venous  pulse  is  also  seen  in  the  superior  and  inferior  vena 
cava  near  to  their  entrance  into  the  heart ;  this  corresponds  to  varia- 
tions of  the  pressure  in  the  right  auricle.  When  the  ventricle  is  con- 
tracting there  is  a  slow  rise,  due  to  the  fact  that  the  blood  cannot  get 
into  the  ventricle,  and  so  distends  the  auricle ;  a  second  short,  sharp 
elevation  of  pressure  is  produced  by  the  auricular  systole.  Altera- 
tions of  venous  pressure  are  also  produced  in  the  great  veins  by  the 
respiratory  movements,  the  pressure  sinking  during  inspiration,  and 
rising  during  expiration. 

The  Vaso-Motor  Nervous  System. 

The  vaso-motor  nervous  system  consists  of  the  vaso-motor  centre 
situated  in  the  bulb,  of  certain  subsidiary  vaso-motor  centres  in  the 
spinal  cord,  and  of  vaso-motor  nerves,  which  are  of  two  kinds — (a) 
those  the  stimulation  of  which  causes  constriction  of  the  vessels; 
these  are  called  vaso-constrictor  nerves ;  (li)  those  the  stimulation  of 
which  causes  dilatation  of  the  vessels ;  these  are  called  vaso-dilator 
nerves. 

The  muscular  structure  of  arteries  was  first  described  by  Henle 
in  1841 ;  but  it  was  not  until  twelve  years  later  that  the  nerves 
supplying  this  muscular  tissue  were  discovered.  The  names  of 
Claude  Bernard,  Brown-Sequard,  and  Schiff  are  specially  connected 
with  this  discovery. 

These  nerves  exert  their  most  important  action  in  the  vessels 
which  contain  relatively  the  greatest  amount  of  muscular  tissue, 
namely,  the  small  arteries  or  arterioles. 

Under  ordinary  circumstances,  the  arterioles  are  maintained  in 
a  state  of  moderate  or  tonic  contraction,  and  this  constitutes  the 
peripheral  resistance,  the  use  of  which  is  to  keep  up  the  arterial 
pressure,  which' must  be  high  enough  to  force  the  blood  through  the 
capillaries  and  veins  in  a  continuous  stream  back  to  the  heart. 

Another  function  which  is  served  by  this  muscular  tissue  is  to 
regulate  the  amount  of  blood  which  flows  through  the  capillaries  of 
any  organ  in  proportion  to  its  needs.  During  digestion,  for  instance, 
it  is  necessary  that  the  digestive  organs  should  be  supplied  with  a 
large  quantity  of  blood:  for  this  purpose  the  arterioles  of  the 
splanchnic  area  are  relaxed,  and  there  is  a  vast  amount  of  blood  in  this 


CH.  XXII.]  THE  VASO-MOTOR  NERVOUS   SYSTEM  301 

area,  and  therefore  a  correspondingly  small  amount  in  other  areas,  such 
as  the  skin ;  this  accounts  for  the  sensation  of  chilliness  experienced 
after  a  full  meal.  The  skin  vessels  form  another  good  example ;  one 
of  the  most  important  uses  of  the  skin  is  to  get  rid  of  the  heat  of 
the  body  in  such  a  way  that  the  body  temperature  shall  remain 
constant ;  when  excess  of  heat  is  produced  there  is  also  an  increase 
in  the  loss  of  heat ;  the  skin  vessels  are  then  dilated,  and  so  more 
blood  is  exposed  on  the  surface,  and  thus  an  increase  in  the  radiation 
of  heat  from  the  surface  is  brought  about.  On  the  other  hand,  when 
it  is  necessary  that  the  heat  produced  should  be  kept  in  the  body, 
the  loss  of  heat  is  diminished  by  a  constriction  of  the  skin  vessels, 
as  in  cold  weather.  The  alteration  of  the  calibre  of  the  vessels  is 
brought  about  by  the  action  of  the  vaso-motor  nervous  system  on 
the  muscular  tissue  of  the  arterioles. 

There  are  certain  organs  of  the  body  in  which  the  necessity  for 
alterations  in  their  blood-supply  does  not  exist.  Such  organs  are, 
heart  itself,  the  lungs,  and  the  brain.  It  is  in  the  vessels  of  these 
organs  that  the  influence  of  vaso-motor  nerves  is  at  a  minimum. 
The  pulmonary  vessels  are  stated  by  Bradford  and  Dean  to  be 
supplied  by  nerves  which  leave  the  cord  in  the  upper  thoracic  region  ; 
but  on  stimulating  these  the  rise  of  pressure  produced  is  extremely 
small ;  it  is  very  doubtful  if  the  fibres  in  question  are  really  vaso- 
constrictors ;  the  small  rise  observed  may  be  partly  or  even  wholly 
due  to  the  acceleration  of  the  heart,  which  is  another  result  of  stimu- 
lating these  nerve-roots. 

The  vaso-motor  centre  lies  in  the  grey  matter  of  the  floor  of  the 
fourth  ventricle ;  it  is  a  few  millimetres  in  length,  reaching  from  the 
upper  part  of  the  floor  to  within  about  4  mm.  of  the  calamus  scrip- 
torius.  The  position  of  this  centre  has  been  discovered  by  the 
following  means :  when  it  is  destroyed  the  tone  of  the  small  vessels 
is  no  longer  kept  up,  and  in  consequence  there  is  a  great  and  universal 
fall  in  arterial  blood-pressure;  when  it  is  stimulated  there  is  an 
increase  in  the  constriction  of  the  arterioles  all  over  the  body,  and 
therefore  a  rise  of  arterial  blood-pressure.  Its  upper  and  lower 
limits  have  been  determined  in  the  following  way:  a  series  of 
animals  is  taken,  and  the  central  nervous  system  divided  in  a 
different  place  in  each;  the  cerebrum  and  cerebellum  may  be  cut 
off  without  affecting  blood-pressure,  the  vaso-motor  centre  must 
therefore  be  below  these ;  if  the  section  is  made  just  above  the 
medulla,  the  blood-pressure  still  remains  high,  and  it  is  not  till  the 
upper  limit  of  the  centre  is  passed  that  the  blood-pressure  falls. 
Similarly,  in  another  series  of  animals,  if  the  cervical  cord  is  cut 
through,  and  the  animal  kept  alive  by  artificial  respiration,  there  is 
an  enormous  fall  of  pressure  due  to  the  influence  of  the  centre  being 
removed  from  the  vessels ;  in  other  experiments  the  section  is  made 


302  THE   CIRCULATION    IN   THE   BLOOD-VESSELS  [CH.  XXII. 

higher  and  higher,  and  the  same  result  noted,  until  at  last  the  lower 
limit  of  the  centre  is  passed,  and  the  fall  of  pressure  is  less  and  less 
marked  the  higher  one  goes  there,  until  in  the  animal  in  which  the 
section  is  made  at  the  upper  boundary  of  the  centre  the  blood- 
pressure  is  not  affected  at  all,  and  the  centre  can  be  influenced 
reflexly  by  the  stimulation  of  afferent  nerves,  the  pressor  and 
depressor  nerves,  which  we  shall  be  considering  immediately. 

After  the  destruction  of  the  vaso-motor  centre  in  the  bulb,  there 
is  a  fall  of  pressure.  If  the  animal  is  kept  alive,  the  vessels  after  a 
time  recover  their  tone,  and  the  arterial  pressure  rises ;  it  rises  still 
more  on  stimulating  the  central  end  of  a  sensory  nerve ;  this  is  due 
to  the  existence  of  subsidiary  vaso-motor  centres  in  the  spinal  cord ; 
for  on  the  subsequent  destruction  of  the  spinal  cord  the  vessels  again 
lose  their  tone  and  the  blood-pressure  sinks. 

The  exact  position  of  the  vaso-motor  centre  in  the  bulb  is  far  from  clear  ;  there 
is  no  special  group  of  cells  there  which  an  anatomist  can  point  to  as  exercising 
this  function,  in  the  same  way  as  he  can  point  to  the  respiratory  or  the  cardio- 
inhibitory  centre.  Possibly  the  cells  are  scattered  over  a  large  area  and  do  not 
occur  in  definite  groups. 

The  fibres  that  leave  these  cells  to  pass  down  the  spinal  cord 
probably  travel  along  the  lateral  columns;  but  here  again  exact 
information  is  lacking,  and  we  do  not  know  whether  or  not  they 
decussate  in  the  bulb  or  elsewhere.  They  terminate  by  arborising 
around  the  cells  in  the  grey  matter  of  the  subsidiary  vaso-motor 
centres,  the  anatomical  position  of  which  is  probably  in  the  cells  of 
the  intermedio-lateral  tract.  From  these  cells  fresh  axis-cylinder 
processes  originate,  which  pass  out  as  the  small  medullated  nerve- 
fibres  in  the  anterior  roots  of  the  spinal  nerves. 

The  general  arrangement  of  the  vaso-motor  nerves  will  have  been 
already  gathered  from  our  description  of  the  Autonomic  Nervous 
System  (Chapter  XVII.);  but  we  may  briefly  recapitulate  the  main 
facts. 

The  vaso-constrictor  nerves  for  the  whole  body  leave  the  spinal 
cord  by  the  anterior  roots  of  the  spinal  nerves  from  the  second 
thoracic  to  the  second  lumbar,  both  inclusive.  They  leave  the  roots 
by  the  white  rami  communicantes,  and  pass  into  the  ganglia  of  the 
sympathetic  chain,  which  lies  on  each  side  of  the  vertebral  column. 
That  is  to  say,  the  small  medullated  or  pre-ganglionic  nerve-fibres 
terminate  by  arborising  around  the  cells  of  these  ganglia,  and  a  fresh 
relay  of  axis-cylinder  processes  from  these  cells  carry  on  the  impulses. 

Those  which  are  destined  for  the  supply  of  the  vessels  of  the  head 
pass  into  the  ganglion  stellatum  or  first  thoracic  ganglion,  thence 
through  the  annulus  of  Vieussens  to  the  inferior  cervical  ganglion, 
and  thence  along  the  sympathetic  trunk  to  their  destination.  Their 
cell-station  is  in  the  superior  cervical  ganglion. 


CH.  XXII.]  VASO-DILATOR   NERVES  303 

The  new  fibres  which  arise  in  the  ganglia  are  usually  non-medul- 
lated,  and  are  termed  post-yanglionic.  Those  for  the  body  wall  and 
limbs  pass  back  from  the  sympathetic  ganglia  to  the  spinal  nerves 
by  the  grey  rami  communicantes,  and  are  distributed  with  the  other 
spinal  nerve-fibres.  The  cell-stations  for  the  upper  limb  fibres  are 
in  the  ganglion  stellatum,  and  for  the  lower  limb  fibres  in  the  lower 
lumbar  and  upper  sacral  ganglia. 

Those  for  the  interior  of  the  body  pass  into  the  various  plexuses 
of  sympathetic  nerves  in  the  thorax  and  abdomen,  and  are  distributed 
to  the  vessels  of  the  thoracic  and  abdominal  viscera.  This  set  includes 
the  most  important  vaso-motor  nerves  of  the  body,  the  splanchnics. 
Their  cell-stations  are  situated  in  the  various  collateral  ganglia. 

The  vaso-dilator  nerves  have  been  stated  to  accompany  those 
just  described,  but  they  are  not  limited  to  the  outflow  from  the 
second  thoracic  to  the  second  lumbar.  Thus,  the  nervi  erigentes 
originate  as  white  rami  communicantes  from  the  second  and  third 
sacral  nerves,  and  the  chorda  tympani,  another  good  example  of  a 
vaso-dilator  nerve,  is  a  branch  of  the  seventh  cranial  nerve. 

Our  knowledge  of  vaso-dilator  nerves  is  limited,  except  in  such 
instances  as  the  two  nerves  just  mentioned.  Equally  deficient  is  our 
information  concerning  vaso-dilator  centres  in  the  central  nervous 
system.  W.  M.  Bayliss,  in  his  search  for  vaso-dilator  fibres  in  the 
dog,  was  not  successful  in  finding  any  for  the  hind  limb  in  the 
abdominal  sympathetic  chain;  but  the  only  fibres,  excitation  of 
which  produced  vascular  dilatation  there,  are  contained  in  the 
posterior  roots.  He  also  found  fibres  in  the  posterior  roots  of  the 
12th  and  13th  thoracic  nerves,  which  act  as  vaso-dilators  of  the 
small  intestine.  Not  only  is  vaso-dilatation  the  result  of  mechanical, 
or  electrical  stimulation  of  these  roots,  but  experiments  are  adduced 
which  show  that  in  normal  reflexes,  such  as  occur  when  the 
depressor  nerve  is  stimulated,  the  dilator  impulses  travel  by  the 
same  route.  This  raises  the  question  whether  the  posterior  roots 
contain  true  efferent  fibres.  The  facts  of  degeneration  show  that 
they  do  not.  Bayliss  is  therefore  driven  to  the  conclusion  that  the 
same  nerve  terminations  in  the  periphery  serve  both  to  take  up 
sensory  impressions  and  to  convey  inhibitory  impulses  to  the 
muscular  structures  in  which  they  end.  In  other  words,  we  have 
here  another  example  which  may  be  added  to  those  previously 
mentioned  (p.  160),  that  nerve-fibres  may  convey  impulses  in  both 
directions.  The  term  antidromic  is  used  by  Bayliss  to  express  the 
fact  that  impulses  may  travel  in  the  reverse  direction  to  that  in 
which  they  usually  pass. 

The  Vaso-motor  centre  can  be  excited  directly  by  induc- 
tion currents;  the  result  is  an  increase  of  arterial  blood-pressure 
owing  to  an  increase  of  the  contraction  of  the  peripheral  arterioles. 


304 


THE   CIRCULATION   IN   THE   BLOOD-VESSELS  [CH.  XXII. 


FIG.  266.— Arterial  blood-pressure  tracing  from  dog  showing  Mayer  waves.    (Sherrington.) 


FIG.  267.— Rise  in  arterial  blood-pressure  produced  by  stimulating  the  central  end  of  a  sensory  nerve  (external  popliteal) 
in  a  cat  under  the  influence  of  morphine  and  curare.  BP,  blood-pressure ;  A,  abscissa  or  base-line ;  T,  time  intervals 
of  5  seconds  ;  E,  signal  line,  the  lowering  of  which  indicates  the  period  of  stimulation  of  the  nerve.  The  size  of  the  figure 
is  slightly  reduced  in  reproduction.  (Sherrington.) 


CIT.  XXIT.]  PRESSOR   AND    DEPRESSOR   NERVES  305 

It  can  also  be  excited  by  the  action  of  poisons  in  the  blood  which 
circulates  through  it ;  thus,  strophanthus  or  digitalis  causes  a  marked 
rise  of  general  arterial  pressure  due  to  the  constriction  of  the  peri- 
pheral vessels  brought  about  by  impulses  from  the  centre. 

It  is  also  excited  by  venous  blood,  as  in  asphyxia;  the  rise  of 
blood-pressure  which  occurs  during  the  first  part  of  asphyxia  is  due 
to  constriction  of  peripheral  vessels ;  the  fall  during  the  last  stage  of 
asphyxia  is  largely  due  to  heart  failure.  When  asphyxia  is  brought 
about  by  the  cessation  of  artificial  respiration  in  a  curarised  animal, 
waves  are  often  observed  on  the  blood-pressure  curve  synchronous 
with  the  normal  rate  of  respiration.  The  respiratory  centre  is 
making  ineffectual  efforts  to  produce  breathing  movements,  and  thus 
it  affects  its  neighbour,  the  vaso-motor  centre,  in  a  parallel  manner. 
Such  waves  are  known  as  Traube-Hering  waves.  One,  however, 
frequently  sees  in  tracings  of  blood-pressure  in  anaesthetised  animals 
larger  waves  which  arise  from  a  slow  rhythmic  action  of  the  vaso- 
motor  centre,  and  which  are  much  slower  in  their  rhythm  than 
those  due  to  respiration.  Fig.  266  represents  a  tracing  from  a  dog 
which  shows  these  waves  (Mayer's  waves).  The  tracing  shows  three 
sets  of  waves,  first  the  oscillations  due  to  the  heart-beats,  next  in 
size  those  produced  by  the  respiratory  movements,  which  in  their 
turn  are  superposed  on  the  prolonged  Mayer  waves. 

The  Vaso-motor  centre  may  be  excited  reflexly. — The  afferent 
impulses  to  the  vaso-motor  centre  may  be  divided  into  pressor  and 
depressor. 

Most  sensory  nerves  are  pressor  nerves.  The  sciatic  or  the  vagus 
nerves  may  be  taken  as  instances ;  when  they  are  divided  and  their 
central  ends  stimulated,  the  result  is  a  rise  of  blood -pressure  due  to 
the  stimulation  of  the  vaso-motor  centre,  and  a  consequent  constric- 
4  tion  of  the  arterioles  .  all  over  the  body,  but  especially  in  the 
splanchnic  area.  Fig.  267  shows  the  result  of  such  an  experiment. 
It  is  necessary  in  performing  the  experiment  to  administer  curare 
as  well  as  an  anaesthetic  to  the  animal,  in  order  to  obviate  reflex 
muscular  struggles,  which  would  themselves  produce  a  rise  in  arterial 
pressure. 

Many  sensory  nerves  also  contain  depressor  fibres ;  these  produce 
the  opposite  effect.  The  most  marked  bundle  of  these  is  known  as 
the  depressor  nerve.  In  most  animals  this  is  bound  up  in  the  trunk 
of  the  vagus ;  but  in  some,  such  as  the  rabbit,  cat,  and  horse,  the  nerve 
runs  up  as  a  separate  branch  from  the  heart  (or,  according  to  some 
recent  observations,  from  the  commencement  of  the  aorta),  and  joins 
the  vagus  or  its  superior  laryngeal  branch,  and  ultimately  reaches  the 
vaso-motor  centre.  When  this  nerve  is  stimulated  (the  vagi  having 
been  previously  divided  to  prevent  reflex  inhibition  of  the  heart),  a 
marked  fall  of  arterial  blood -pressure  is  produced  (see  fig.  268). 

U 


306 


THE   CIRCULATION   IN   THE   BLOOD-VESSELS  [CII.  XXTI. 


Stimulation  of  this  nerve  affects  the  vaso-motor  centre  in  such  a  way 
that  the  normal  constrictor  impulses  that  pass  down  the  vaso-con- 
strictor  nerves  are  inhibited.  The  fall  of  pressure  is  very  slight  after 
section  of  the  splanchnic  nerves,  showing  that  the  splanchnic  area  is 
the  part  of  the  body  most  affected.  The  normal  function  of  this 


B.P. 


FIG.  263. — Tracing  of  arterial  blood-pressure  showing  the  effect  of  stimulating  the  central  end  of  the  Depressor  nervr 
a  cat.     The  letters  prefixed  to  the  various  lines  have  the  same  meaning  as  in  tig.  2(37.    (Sherrington.) 


nerve  is  to  adapt  the  peripheral  resistance  to  the  heart's  action :  if 
the  constriction  of  the  arterioles  is  too  high  for  the  heart  to  overcome, 
an  impulse  by  this  nerve  to  the  vaso-motor  centre  produces  reflexly 
a  lessening  of  the  peripheral  resistance. 

N.B. — The  term  depressor  should  be  carefully  distinguished  from 
inhibitory ;  stimulation  of  the  peripheral  end  of  the  vagus  produces 
a  fall  of  blood  pressure  due  to  inhibition  (slowing  or  stoppage)  of  the 
heart  (see  figs.  246  and  247);  stimulation  of  the  central  end  of  the 


CH.  XXII.]  EXPERIMENTS   ON  VASO-MOTOR   NERVES  307 

depressor  nerve  produces  a  lowering  of  blood-pressure  for  a  different 
reason,  namely,  a  reflex  relaxation  of  the  splanchnic  arterioles. 

Experiments  on  Vaso-motor  nerves. — The  experiments  on  the 
vaso-motor  nerves  are  similar  to  those  performed  on  other  nerves 
when  one  wishes  to  ascertain  their  functions.  They  consist  of 
section  and  excitation. 

Section  of  a  vaso-constrictor  nerve,  such  as  the  splanchnic,  causes 
a  loss  of  normal  arterial  tone,  and  consequently  the  part  supplied  by 
the  nerve  becomes  flushed  with  blood.  Stimulation  of  the  peripheral 
end  causes  the  vessels  to  contract  and  the  part  to  become  compara- 
tively pale  and  bloodless.  This  can  be  very  readily  demonstrated 
on  the  ear  of  an  anaesthetised  rabbit.  This  is  a  classical  experiment 
associated  with  the  name  of  Claude  Bernard.  Division  of  the  cervical 
sympathetic  produces  an  increased  redness  of  the  side  of  the  head, 
and  looking  at  the  ear,  the  transparency  of  which  enables  one  to  follow 
the  phenomena  easily,  the  central  artery  with  its  branches  is  seen  to 
become  larger,  and  many  small  branches  not  previously  visible  come 
into  view.  The  ear  feels  hotter,  though  this  effect  soon  passes  off  as 
the  exposure  of  a  large  quantity  of  blood  to  the  air  causes  a  rapid 
loss  of  heat.  On  stimulating  the  peripheral  end  of  the  cut  nerve, 
the  ear  resumes  its  normal  condition,  and  then  becomes  paler  than 
usual  owing  to  excessive  constriction  of  the  vessels. 

Section  of  a  vaso-dilator  nerve,  such  as  the  chorda  tympani,  pro- 
duces no  effect  on  the  vessels,  but  stimulation  of  its  peripheral  end 
causes  great  enlargement  of  all  the  arterioles,  so  that  the  submaxillary 
gland  and  the  neighbouring  parts  supplied  by  the  nerve  become  red 
and  gorged  with  blood,  and  the  pulse  is  propagated  through  to  the 
veins ;  the  circulation  through  the  capillaries  may  be  so  rapid  that 
the  blood  is  arterial  in  colour  in  the  veins.  Another  effect,  free 
secretion  of  saliva,  we  shall  study  in  connection  with  that  subject. 

Other  examples  of  vaso-dilator  nerves  are  the  nervi  erigentes  to 
the  erectile  tissue  of  the  penis,  etc.,  and  of  the  lingual  nerve  to  the 
vessels  of  the  tongue. 

It  is,  however,  probable  that  all  the  vessels  of  the  body  receive 
both  constrictor  and  dilator  nerves.  But  the  presence  of  the  latter 
is  difficult  to  determine  unless  they  are  present  in  excess ;  if  they 
are  not,  stimulation  affects  the  constrictors  most.  The  effect  of 
section  is  also  inconclusive ;  for  if  a  mixed  nerve  is  cut,  the  only  effect 
observed  is  a  dilatation  due  to  removal  of  the  tonic  constrictor  influence. 

To  solve  this  difficult  problem,  three  methods  are  in  use : — 

1.  The  method  of  degeneration. — If  the  sciatic  nerve  is  cut,  the 
vessels  of  the  limb  dilate.  This  passes  off  in  a  day  or  two.  If  the 
peripheral  end  of  the  nerve  is  then  stimulated,  the  vessels  are  dilated, 
as  the  constrictor  fibres  degenerate  earliest,  and  so  one  gets  a  result 
due  to  the  stimulation  of  the  still  intact  dilator  fibres, 


308  THE   CIRCULATION   IN   THE   BLOOD-VESSELS  [Oil.  XXII 

2.  The  method  of  slowly  interrupted  shocks. — If  a  mixed  nerve  is 
stimulated  with  the  usual  rapidly  interrupted  faradic  current,  the 
effect  is  constriction ;  but  if  the  induction  shocks  are  sent  in  at  long 
intervals   (e.g.,   at  intervals   of   a    second),  vaso-dilator   effects    are 
obtained.     This  can  be  readily  demonstrated  on  the  kidney  vessels 
by  stimulation  of  the  anterior  root  of  the  eleventh  thoracic  nerve  in 
the  two  ways  just  indicated. 

By  studying  the  rate  of  flow  of  the  blood  through  the  submaxillary 
gland,  in  which  the  vaso-constrictor  and  dilator  fibres  run  separate 
courses,  it  has  been  shown  that  if  both  sets  of  fibres  are  simultaneously 
excited,  constriction  is  produced  during  the  stimulation,  while  marked 
dilatation  follows  after  the  stimulation  has  ceased.  Excitation  of  the 
constrictors  alone  is  not  followed  by  dilatation.  These  results  explain 
the  mode  of  action  of  slowly  interrupted  shocks,  for  with  each  there 
will  only  be  a  very  slight  constriction,  while  the  dilator  effects  which  run 
a  much  slower  course  will  be  summed  up  to  produce  a  marked  effect. 

3.  The  influence  of  temperature.—  Exposure  to  a  low  temperature 
depresses  the   constrictors  more   than   the  dilators.      If   the  leg  is 
placed  in  ice-cold  water,  stimulation  of  the  sciatic,  even  if  it  has  only 
been  recently  divided,  produces  a  flushing  of  the  skin  with  blood. 

Plethysmography. 

The  action  of  vaso-motor  nerves  can  be  studied  in  another  way 
than  bv  the  use  of  various  forms  of  manometer,  which  is  the  only 


FIG.  269. — Plethysmograph.  By  means  of  this  apparatus,  the  alteration  in  volume  of  the  arm  E,  which 
is  enclosed  in  a  glass  tube  A,  filled  with  fluid,  the  opening  through  which  it  passes  being  firmly 
closed  by  a  thick  gutta-percha  band  F,  is  communicated  to  the  lever  r>,  and  registered  by  a  recording 
apparatus.  The  fluid  in  A  communicates  with  that  in  B,  the  upper  limit  of  which  is  above  that  in 
A.  The  alterations  in  volume  are  due  to  alterations  in  the  blood  contained  in  the  arm.  When 
the  volume  is  increased,  fluid  passes  out  of  the  glass  cylinder,  and  the  lever  D  also  is  raised,  and 
when  a  decrease  takes  place  the  fluid  returns  again  from  B  to  A.  It  will  therefore  be  evident  that 
the  apparatus  is  capable  of  recording  alterations  of  the  volume  of  blood  in  the  arm. 

method  we  have  considered  so  far.  The  second  method,  which  is 
often  used  together  with  the  manometer,  consists  in  the  use  of  an 
instrument  which  records  variations  in  the  volume  of  any  limb,  or 


Oil.  XXII.]  THE   ONCOMETER  309 

organ  of  an  animal.  Such  an  instrument  is  called  a  plethysmograph. 
One  of  these  instruments  applied  to  the  human  arm  is  shown  in  the 
accompanying  figure  (fig.  269). 

Every  time  the  arm  expands  with  the  heart's  systole,  a  little  of 
the  fluid  in  the  plethysmograph  is  expelled  and  raises  the  lever. 
Variations  in  volume  due  to  respiration  are  also  seen  in  the  tracing. 
An  air  plethysmograph  connected  to  a  sensitive  recorder  gives  equally 
good  results. 

A  study  of  the  volume  pulse  shows  it  to  possess  the  same  main 
characters  (for  instance,  a  dicrotic  wave  on  the  downstroke)  which 
we  have  already  described  in  connection  with  the  velocity  pulse,  and 
the  pressure  pulse  (see  p.  288). 

When  the  same  method  in  a  modified  form  is  applied  to  such 
viscera  as  the  kidney  or  spleen,  the  instrument  is  generally  called 
an  oncometer.  The  earliest  oncometers  were  made  by  Koy. 

Boy's  oncometer  (figs.  270  and  271)  consists  of  a  metal  capsule, 
of  shape  suitable  to  enclose  the  organ:  its  two  halves  are  jointed 
together,  and  fit  accurately  except  at  one  opening  which  is  left  for 
the  vessels  of  the  organ.  A  delicate  membrane  is  attached  to  the 
rim  of  each  half,  the  space  between  which  and  the  metal  is  filled 
with  warm  oil.  The  tube  from  the  oncometer  is  connected  to  the 
oil-containing  cavity  of  the  recorder  by  a  tube  also  containing  oil. 
An  increase  in  the  volume  of  the  organ  squeezes  the  oil  out  of  the 
oncometer  into  the  recorder,  and  so  produces  a  rise  of  its  piston  and 
lever ;  a  contraction  of  the  organ  produces  a  fall  of  the  lever. 

These  elaborate  instruments  have  now  been  entirely  superseded 
by  air  oncometers,  and  Schafer  was  the  first  to  employ  an  air 
oncometer  in  his  work  on  the  spleen. 

If  now  we  are  investigating  the  action  of  the  anterior  root  of 
eleventh  thoracic  nerve  on  the  vessels  of  the  kidney,  a  tracing  is  taken 
simultaneously  of  the  arterial  blood-pressure  in  the  carotid,  and  of 
the  volume  of  the  kidney  by  the  oncometer.  On  stimulating  the 
nerve  rapidly,  there  is  a  slight  rise  of  arterial  pressure,  but  a  large 
fall  of  the  recording  lever,  showing  that  the  kidney  has  diminished 
in  volume.  It  is  evident  that  there  must  be  an  active  contraction  of 
the  arterioles  of  the  kidney,  causing  it  to  diminish  in  size,  for  the 
blood-pressure  tracing  (which  is  taken  as  a  control  to  be  sure  the 
changes  are  not  otherwise  produced)  shows  that  there  is  no  failure  of 
the  heart's  activity  to  account  for  it. 

We  shall  return  to  the  subject  of  the  oncometer  in  connection 
with  the  spleen  and  the  kidney.  We  may,  however,  say  in  passing 
what  a  very  important  experimental  method  plethysmography  is 
becoming.  Since  the  introduction  of  air  oncometers,  the  method  is 
remarkably  easy  to  apply,  and  it  is  now  part  of  the  routine  practice 
of  physiologists,  when  they  are  investigating  the  action  of  a  drug, 


310  THE  CIRCULATION   IN   THE   BLOOD-VESSELS  [CH.  XXlt. 

or  of  a  nerve,  on  any  organ,  to  record  its  volume  changes  by  the 
plethysmographic  method.     Thus,  the  salivary  glands,  lobes  of  the 


FIG.  270.— Diagram  of  Roy's  Oncometer.  a  represents  the  kidney  enclosed  in  a  metal  box,  which  opens 
by  hinge  /;  b,  the  renal  vessels  and  duct.  Surrounding  the  kidney  are  two  chambers  formed  by 
membranes,  the  edges  of  which  are  firmly  fixed  by  being  clamped  between  the  outside  metal  capsule, 
and  one  (not  represented  in  the  figure)  inside,  the  two  being  firmly  screwed  together  by  screws  at  h, 
and  below.  The  membranous  chamber  below  is  filled  with  a  varying  amount  of  warm  oil,  according 
to  the  size  of  the  kidney  experimented  with,  through  the  opening,  then  closed  with  the  plug  i. 
After  the  kidney  has  been  enclosed  in  the  capsule,  the  membranous  chamber  above  is  filled  with 
warm  oil  through  the  tube  e,  which  is  then  closed  by  a  tap  (not  represented  in  the  diagram) ;  the 
tube  d  communicates  with  a  recording  apparatus,  and  any  alteration  in  the  volume  of  the  kidney 
is  communicated  by  the  oil  in  the  tube  to  the  chamber  d  of  the  Oncograph,  fig.  271. 


FIG.  271 — Roy's  Oncograph,  or  apparatus  for  recording  alterations  in  the  volume  of  the  kidney,  etc., 
as  shown  by  the  oncometer — a,  upright,  supporting  recording  lever  I,  which  is  raised  or  lowered  by 
needle  b,  which  works  through/,  and  which  is  attached  to  the  piston  e,  working  in  the  chamber  d, 
with  which  the  tube  from  the  oncometer  communicates.  The  oil  is  prevented  from  being  squeezed 
out  as  the  piston  descends  by  a  membrane,  which  is  clamped  between  the  ring-shaped  surfaces  of 
cylinder  by  the  screw  i  working  upwards  ;  the  tube  li  is  for  filling  the  instrument. 

liver  or  lung,  the  limbs,  the  kidney,  spleen,  a  coil  of  intestine,  etc., 
can  each  be  easily  enclosed  in  an  appropriately  shaped  gutta-percha 


CH.  XXIT.]  PATHOLOGICAL  CONDITIONS  311 

box,  covered  with  a  glass  plate  made  air-tight  with  vaseline.  There 
are  always  two  openings  to  such  a  box,  one  to  allow  the  vessels  and 
nerves  to  enter  (leakage  of  air  around  these  is  prevented  by  packing 
with  cotton-wool  soaked  in  vaseline) ;  the  other  opening  is  filled  up 
with  a  piece  of  glass  tubing  which  is  connected  by  an  india-rubber 
tube  to  the  recording  apparatus  (see  fig.  272).  The  most  delicate  of 


FIG.  272.— Apparatus  for  obtaining  splenic  curves,  s,  Spleen  in  oncorneter  o,  which  is  made  of  gutta- 
percha,  and  covered  with  a  glass  plate  (G.P.)  luted  on  with  vaseline.  M  is  the  splenic  mesentery 
containing  vessels  and  nerves ;  this  passes  through  a  slit  in  the  base  of  the  oncometer  which  is 
made  air-tight  with  vaseline.  The  oncometer  is  connected  to  the  flexible  bellows  (B)  by  the  india- 
rubber  tube  (R),  the  side  tube  (T)  being  closed  during  an  experiment  by  a  piece  of  glass  rod.  The 
recording  lever  (L)  writes  on  a  revolving  drum. 

the  volume  recorders  is  the  bellows-recorder  of  Brodie  or  the  piston 
recorder  of  Hiirthle. 

Of  all  the  oncometers,  I  am  inclined  to  believe  that  the  intestinal 
oncometer  is  the  most  instructive,  because  the  coil  of  intestine  under 
observation  gives  a  truer  record  of  what  is  occurring  in  that  important 
area  called  the  splanchnic  area,  than  any  other  abdominal  organ. 


Pathological  Conditions. 

The  vaso-rnotor  nervous  system  is  influenced  to  some  extent  by 
conditions  of  the  cerebrum,  some  emotions,  such  as  fear,  causing 
pallor  (vaso-constriction),  and  others  causing  blushing  (vaso- 
dilatation). 

It  is  almost  impossible  to  over-estimate  the  importance  of  the 
study  of  vaso-motor  phenomena  as  a  means  of  explaining  certain 
pathological  conditions;  our  knowledge  of  the  processes  concerned 
in  inflammation  is  a  case  in  point. 

Disorders  of  the  vessels  due  to  vaso-motor  disturbances  are 
generally  called  angio-neuroses.  Of  these  we  may  mention  the 
following : — 

Tache  cerebrate  is  duo  to  abnormal  sensitiveness  of  the  vascular 


312  THE   CIRCULATION    IN   THE   BLOOD-VESSELS  [CIJ.  XXII. 

nerves ;  drawing  the  finger-nail  across  the  skin  causes  an  immediate 
wheat,  or  at  least  a  red  mark  that  lasts  a  considerable  time.  At  one 
time  this  was  considered  characteristic  of  affections  of  the  cerebral 
meninges  such  as  tubercular  meningitis,  and  was  consequently  called 
the  "  meningeal  streak."  It,  however,  occurs  in  a  variety  of  patho- 
logical conditions  of  the  nervous  system,  both  cerebral  and  spinal. 

In  certain  conditions  which  lead  to  angina  pectoris  the  pain  in 
the  heart  is  in  part  due  to  its  being  unable  to  overcome  an  immense 
peripheral  resistance,  and  the  condition  is  relieved  by  the  adminis- 
tration of  such  drugs  as  amyl-nitrite  or  nitroglycerin,  which  relax  the 
vessels  and  cause  universal  blushing. 

Raynaud's  disease  is  one  in  which  there  is  a  localised  constriction 
of  the  vessels  which  is  so  effectual  as  to  entirely  cut  off  the  blood 
supply  to  the  capillary  areas  beyond,  and  if  this  lasts  any  considerable 
time  may  lead  to  gangrene  of  the  parts  in  question. 

Local  Peculiarities  of  the  Circulation. 

The  most  remarkable  peculiarities  attending  the  circulation  of  blood  through 
different  organs  are  observed  in  the  cases  of  the  brain,  erectile  organs,  lungs,  liver, 
spleen,  and  kidneys. 

In  the  Brain. — The  brain  must  always  be  supplied  with  blood,  for  otherwise  im- 
mediate loss  of  consciousness  would  follow.  Hence,  to  render  accidental  oblitera- 
tion almost  impossible,  four  large  arteries  are  supplied  to  the  brain,  and  these  anas- 
tomose together  in  the  circle  of  Willis.  The  two  vertebral  arteries  are,  moreover, 
protected  in  bony  canals.  Two  of  the  brain  arteries  can  be  tied  in  monkeys,  and 
three  or  even  all  four  in  dogs,  without  the  production  of  serious  symptoms.  In  the 
last  case  enough  blood  reaches  the  brain  by  branches  from  the  superior  intercostal 
arteries  to  the  anterior  spinal  artery.  The  sudden  obliteration  of  one  carotid  artery 
in  man  may  in  some  cases  produce  epileptiform  spasms ;  the  sudden  occlusion  of 
both  occasions  loss  of  consciousness.  Uniformity  of  supply  is  further  ensured  by 
the  arrangement  of  the  vessels  in  the  pia  mater,  in  which,  previous  to  their  distribu- 
tion to  the  substance  of  the  brain,  the  large  arteries  break  up  and  divide  into 
innumerable  minute  branches  ending  in  capillaries,  which,  after  frequent  communi- 
cation with  one  another,  enter  the  brain  and  carry  into  nearly  every  part  of  it  uni- 
form and  equable  streams  of  blood.  The  arteries  are  enveloped  in  a  special 
lymphatic  sheath.  The  arrangement  of  the  veins  within  the  cranium  is  also  peculiar. 
The  large  venous  trunks  or  sinuses  are  formed  so  as  to  be  scarcely  capable  of  change 
of  size ;  and  composed,  as  they  are,  of  the  tough  tissue  of  the  dura  mater,  and,  in 
some  instances,  bounded  on  one  side  by  the  bony  cranium,  they  are  not  compres- 
sible by  any  force  which  the  fulness  of  the  arteries  might  exercise  through  the  sub- 
stance of  the  brain  ;  nor  do  they  admit  of  distension  when  the  flow  of  venous  blood 
from  the  brain  is  obstructed.  No  valves  are  placed  between  the  vertebral  veins  and 
the  vena  cava  ;  the  vertebral  veins  anastomose  with  the  cerebral  sinuses.  Hence  on 
squeezing  the  thorax  and  abdomen,  venous  blood  can  be  pressed  from  those 
parts  out  of  any  opening  made  into  the  longitudinal  sinus.  Expiration  acts  in  the 
same  way  ;  it  raises  the  cerebral  venous  pressure  ;  if  the  skull  wall  is  defective  the 
brain  expands  owing  to  the  distension  of  its  capillaries  during  the  expiratory  act. 
The  exposed  brain  also  expands  with  each  systole  of  the  heart.  Owing  to  the  fact 
that  the  brain  lies  enclosed  in  the  cranium,  the  arterial  pulse  is  transmitted  through 
the  brain  substance  to  the  cerebral  veins,  and  so  the  blood  issues  from  these  in  pulses. 

Since  the  brain  is  enclosed  in  the  rigid  cranium  the  volume  of  blood  in  the 
cerebral  vessels  cannot  alter  unless  the  volume  of  the  other  cranial  con  tents  alters  in 
the  opposite  sense. 

These  conditions  of  the  brain  and  skull  led  Monro  and  Kellie  many  years  ago 


CH.  XXII.]  THE   CIRCULATION    IN  THE  BRAIN  313 

to  advance  the  opinion  that  the  quantity  of  blood  in  the  brain  must  be  the  same  at 
all  times.  This  doctrine  has  been  frequently  disputed,  and  many  have  advanced 
the  theory  that  increase  or  diminution  of  the  blood  is  accompanied  with  simultane- 
ous diminution  or  increase  of  the  cerebro-spinal  fluid,  so  that  the  contents  of  the 
cranium  are  kept  uniform  in  volume.  But  the  recent  work  of  Leonard  Hill  has 
shown  that  the  Monro-Kellie  doctrine  is  in  the  main  true.  Histological  evidence 
has  recently  been  obtained  of  the  existence  of  nerve  plexuses  round  the  pial 
arteries.  The  arteries  are  muscular,  and  the  nerves  therefore  are  most  probably 
vaso-motor  in  function.  Experimental  evidence  so  far,  however,  has  not  estab- 
lished that  the  action  of  these  nerves  is  a  marked  one ;  the  cerebral  circulation 
passively  follows  the  slightest  changes  in  aortic  and,  more  especially,  vena  cava 
pressure,  and  no  active  vaso-motor  change  has  been  conclusively  proved.  The 
velocity  of  blood-flow  through  the  brain  is  thus  influenced  markedly  by  the  con- 
dition of  the  vessels  of  the  splanchnic  area.  If  these  are  unduly  dilated,  the  blood- 
flow  through  the  brain  may  be  so  reduced  as  to  lead  to  fainting.  Thus,  to  restore 
a  fainting  person  the  head  must  be  lowered  between  the  knees.  Muscular 
exercise,  by  returning  blood  to  the  heart  from  the  veins  of  the  lower  parts  of  the 
body,  conduces  to  the  maintenance  of  an  efficient  cerebral  circulation. 

It  is  not  the  volume  of  the  blood  but  the  velocity  of  flow  which  is  altered  in 
the  brain  by  changes  in  the  general  circulation.  The  brain  with  its  circulating 
blood  almost  entirely  rills  the  cranial  cavity  in  the  living  animal ;  that  is,  there  is 
no  more  cerebro-spinal  fluid  there  than  is  sufficient  to  moisten  the  membranes. 
Cerebro-spinal  fluid  escapes  into  the  lymphatics,  and  possibly  also  into  the  veins, 
at  any  pressure  above  the  cerebral  venous  pressure ;  the  tension  of  this  fluid  and 
the  pressure  in  the  veins  are  therefoie  always  the  same.  The  fluid  is  secreted  by 
the  epithelium  covering  the  vascular  fringes  of  the  choroid  plexuses  in  the  ven- 
tricles of  the  brain  (see  p.  172),  and  is  absorbed  mainly  by  the  lymphatics.  There 
is  not  enough  of  this  absorbable  fluid  present  to  allow  of  more  than  a  slight  increase 
of  the  volume  of  blood  in  the  brain.  If  the  aortic  pressure  rises  and  the  vena  cava 
pressure  remains  constant,  the  conditions  in  the  brain  are  as  follows  :— 

More  blood  in  the  arteries,  less  in  the  veins,  increased  velocity  of  flow.    . 

While  if  the  aortic  pressure  remains  constant  and  the  vena  cava  pressure  rises, 
the  conditions  are  : — 

Less  blood  in  the  arteries,  more  in  the  veins,  diminished  velocity  of  flow. 

The  brain  presses  against  the  cranial  wall  with  a  pressure  equal  to  that  in  the 
cerebral  capillaries.  A  foreign  body  introduced  within  the  cranium,  such  as  a 
blood-clot  or  depressed  bone,  produces  local  anaemia  of  the  brain,  by  occupying  the 
room  of  the  blood.  So  soon  as  the  capillaries  are  thus  obliterated  the  pressure  is 
raised  to  arterial  pressure.  This  local  increase  of  cerebral  tension  cannot  be  trans- 
mitted by  the  cerebro-spinal  fluid,  because  this  fluid  can  never  be  retained  in  the 
meningeal  spaces  at  a  tension  higher  than  that  of  the  cerebral  veins,  but  is 
immediately  reabsorbed.  The  anatomical  arrangements  of  the  tentorium  cerebelli 
and  the  falciform  ligaments  are  such  as  to  largely  prevent  the  transmission  through 
the  brain-substance  of  a  local  increase  of  pressure.  There  is  complete  pressure 
discontinuity  between  the  cranial  and  vertebral  cavities.  The  serious  results  that 
follow  cerebral  compression  are  primarily  due  to  obliteration  of  the  blood-vessels, 
and  consequent  anaemia  of  the  brain.  A  very  small  foreign  body  will,  if  situated 
in  the  region  of  the  bulb,  produce  the  gravest  symptoms.  For  the  centres  which 
control  the  vascular  and  respiratory  systems  are  rendered  anaemic  thereby.  The 
cerebral  hemispheres  may,  on  the  other  hand,  be  compressed  to  a  large  extent 
without  causing  a  fatal  result.  The  major  symptoms  of  compression  arise  as  soon 
as  any  local  increase  of  pressure  is  transmitted  to  the  bulb  and  causes  anaemia 
there. 

In  Erectile  Structures. — The  instances  of  greatest  variation  in  the  quantity  of 
blood  contained,  at  different  times,  in  the  same  organs,  are  found  in  certain 
structures  which,  under  ordinary  circumstances,  are  soft  and  flaccid,  but,  at  certain 
times,  receive  an  unusually  large  quantity  of  blood,  become  distended  and  swollen 
by  it,  and  pass  into  the  state  which  has  been  termed  erection.  Such  structures  are 
the  corpora  cavernosa  and  corpus  sponyiosum  of  the  penis  in  the  male,  and  the 
clitoris  in  the  female ;  and,  to  a  less  degree,  the  nipple  of  the  mammary  gland  in 


314  THE   CIRCULATION   IN   THE  BLOOD-VESSELS  [CH.  XXII. 

both  sexes.  The  corpus  cavernosum  penis,  which  is  the  best  example  of  an  erectile 
structure,  has  an  external  fibrous  membrane  or  sheath  ;  and  from  the  inner  surface 
of  the  latter  are  prolonged  numerous  fine  lamellae  which  divide  its  cavity  into  small 
compartments.  Within  these  is  situated  the  plexus  of  veins  upon  which  the 
peculiar  erectile  property  of  the  organ  mainly  depends.  It  consists  of  short  veins 
which  very  closely  interlace  and  anastomose  with  each  other  in  all  directions,  and 
admit  of  great  variations  of  size,  collapsing  in  the  passive  state  of  the  organ,  but 
capable  of  an  amount  of  dilatation  which  exceeds  beyond  comparison  that  of  the 
arteries  and  veins  which  convey  the  blood  to  and  from  them.  The  strong  fibrous 
tissue  lying  in  the  intervals  of  the  venous  plexuses,  and  the  external  fibrous 
membrane  or  sheath  with  which  it  is  connected,  limit  the  distension  of  the  vessels, 
and  during  the  state  of  erection,  give  to  the  penis  its  condition  of  tension  and  firm- 
ness. The  same  general  condition  of  vessels  exists  in  the  corpus  spongiosum 
urethras,  but  around  the  urethra  the  fibrous  tissue  is  much  weaker  than  around  the 
body  of  the  penis,  and  around  the  glans  there  is  none.  The  venous  blood  is 
returned  from  the  plexuses  by  comparatively  small  veins.  For  all  these  veins  one 
condition  is  the  same  ;  namely,  that  they  are  liable  to  the  pressure  of  muscles  when 
they  leave  the  penis.  The  muscles  chiefly  concerned  in  this  action  are  the  erector 
penis  and  accelerator  urinae.  Erection  results  from  the  distension  of  the  venous 
plexuses  with  blood.  The  principal  exciting  cause  in  the  erection  of  the  penis  is 
nervous  irritation,  originating  in  the  part  itself,  and  derived  reflexly  from  the  brain 
and  spinal  cord.  The  nervous  influence  is  communicated  to  the  penis  by  the  pudic 
nerves,  which  ramify  in  its  vascular  tissue ;  and  after  their  division  the  penis  is 
no  longer  capable  of  erection. 

Erection  is  not  complete,  nor  maintained  for  any  time  except  when,  together 
with  the  influx  of  blood,  the  muscles  mentioned  contract,  and  by  compressing  the 
veins^stop  the  efflux  of  blood,  or  prevent  it  from  being  as  great  as  the  influx. 

The  circulation  in  the  Lungs,  Liver,  Spleen,  and  Kidneys  will  be  described  in  our 
study  of  those  organs. 


CHAPTER  XXIII 

LYMPH  AND  LYMPHATIC  GLANDS 

As  the  blood  circulates  through  the  capillary  blood-vessels,  some  of 
its  liquid  constituents  exude  through  the  thin  walls  of  these  vessels, 
carrying  nutriment  to  the  tissue  elements.  This  exudation  is  called 
lymph;  it  receives  from  the  tissues  the  products  of  their  activity, 
and  is  collected  by  the  lymph  channels,  which  converge  to  the  thoracic 
duct — the  main  lymphatic  vessel — and  thus  the  lymph  once  more 
re-enters  the  blood-stream  near  to  the  entrance  of  the  large  systemic 
veins  into  the  right  auricle. 

Lymph  is  a  fluid,  which  comes  into  much  more  intimate  relation- 
ship with  metabolic  processes  in  the  tissues  than  the  blood ;  in  fact, 
there  is  only  one  situation — the  spleen — where  the  blood  comes  into 
actual  contact  with  the  elements — that  is,  cells,  fibres,  etc. — of  a 
tissue. 

Composition  of  Lymph. 

Lymph  is  alkaline;  its  specific  gravity  is  about  1015,  and  after 
it  leaves  the  vessels  it  clots,  forming  a  colourless  coagulum  of  fibrin. 
It  is  like  blood-plasma  in  composition,  only  diluted  so  far  as  its 
protein  constituents  are  concerned.  This  is  due  to  the  fact  that 
proteins  do  not  pass  readily  through  membranes.  The  proteins 
present  are  called  fibrinogen,  serum  globulin,  and  serum  albumin; 
these  we  shall  study  with  the  blood-plasma.  The  salts  are  similar 
to  those  of  blood-plasma,  and  are  present  in  about  the  same  propor- 
tions. Chlorides,  however,  are  more  abundant  in  lymph  than  in 
blood.  The  waste  products,  such  as  carbonic  acid  and  urea,  are  also 
more  abundant.  The  amount  of  solids  dissolved  in  lymph  is  about 
6  per  cent.,  more  than  half  of  which  is  protein  in  nature. 

When  examined  with  the  microscope  the  transparent  lymph  is 
found  to  contain  colourless  corpuscles,  which  are  called  lymphocytes  ; 
these  are  cells  with  large  nuclei  and  comparatively  little  protoplasm. 
They  pass  with  the  lymph  into  the  blood,  and  constitute  there  one 
of  the  varieties  of  colourless  blood  corpuscles. 

All  the  lymphatics  pass  at  some  point  of  their  course  through 

315 


316 


LYMPH   AND   LYMPHATIC    GLANDS 


[CH.  XXIIL 


lymphatic  glands,  which  are  the  factories  of  these  corpuscles.  Lym- 
phocytes also  pass  into  the  lymph-stream  wherever  lymphoid  tissue 
is  found,  as  in  the  tonsils,  thymus,  Malpighian  bodies  of  the  spleen, 
Peyer's  patches,  and  the  solitary  glands  of  the  intestine.  The  lymph 
that  leaves  these  tissues  is  richer  in  lymph-cells  than  that  which 
enters  them. 

When  lymph  is  collected  from  the  thoracic  duct  after  a  meal 
containing  fat,  it  is  found  to  be  milky.  This  is  due  to  the  presence 
in  the  lymph  of  minutely  subdivided  fat  particles  absorbed  from  the 
interior  of  the  alimentary  canal.  The  lymph  is  then  called  chyle. 
The  fat  particles  constitute  what  used  to  be  called  the  molecular  basis 
of  chyle.  If  the  abdomen  is  opened  during  the  process  of  fat  absorp- 
tion, the  lymphatics  are  seen  as  white  lines,  due  to  their  containing 
this  milky  fluid.  They  are  consequently  called  lacteals. 

The  structure  and  arrangement  of  the  lymphatic  vessels  are  given 
in  Chapter  XIX.,  and  we  have  now  to  study  the  structure  of 

The  Lymphatic  Glands. 

Lymphatic  glands  are  round  or  oval  bodies  varying  in  size  from 
a  hemp-seed  to  a  bean,  interposed  in  the  course  of  the  lymphatic 


FIG.  273.— Diagrammatic  section  of  lymphatic  gland,  a.l.,  Afferent;  e.l.,  efferent  lymphatics;  C, 
cortical  substance ;  l.h.,  lymphoid  tissue;  Z.s.,  lymph  -path;  c.,  fibrous  capsule  sending  in  trabeculse 
tr.  into  the  substance  of  the  gland.  (Sharpey.) 

vessels,  and  through  which  the  lymph  passes  in  its  course  to  be  dis- 
charged into  the  blood-vessels.     They  are  found  in  great  numbers  in 


GIL  XXITI.] 


LYMPHATIC   GLANDS 


317 


the  mesentery,  and  along  the  great  vessels  of  the  abdomen,  thorax, 
and  neck ;  in  the  axilla  and  groin ;  a  few  in  the  popliteal  space,  but 
not  further  down  the  leg,  and  in  the  arm  as  far  down  as  the  elbow. 

A  lymphatic  gland  is  covered  externally  by  a  capsule  of  con- 
nective tissue,  generally  containing  some  unstriped  muscle.  At  the 
inner  side  of  the  gland,  which  is  somewhat  concave  (hilus),  the 
capsule  sends  inwards  processes  called  trabeculce  in  which  the  blood- 
vessels are  contained,  and  these  join  with  other  processes  prolonged 
from  the  inner  surface  of  the 
part  of  the  capsule  covering  the 

convex    or    outer    part    of    the  j  I 

gland ;    they    have    a    structure  ~MHSml     \ 

similar  to  that  of  the  capsule, 
and  entering  the  gland  from  all 
sides,  and  freely  communicating, 
form  a  fibrous  scaffold  ing.  The 
interior  of  the  gland  is  seen  on 
section,  even  when  examined 
with  the  naked  eye,  to  be  made 
up  of  two  parts,  an  outer  or 
cortical,  which  is  light  coloured, 
and  an  inner  or  medullary  por- 
tion of  redder  appearance  (fig. 
273).  In  the  outer  part,  or 
cortex,  of  the  gland  the  intervals 
between  the  trabeculse  are  large 
and  regular;  they  are  termed 
alveoli ;  whilst  in  the  more 
central  or  medullary  part  is  a 
finer  meshwork  formed  by  an 
irregular  anastomosis  of  the  tra- 
becular  processes.  Within  the 
alveoli  of  the  cortex  and  in  the 
meshwork  formed  by  the  trabec- 
ulaa  in  the  medulla,  is  contained 


FIG.  274.— A  small  portion  of  medullary  substance 
from  a  mesenteric  gland  of  the  ox.  d,  d,  Trabe- 
culae  ;  a,  part  of  a  cord  of  lymphoid  tissue  from 
which  all  but  a  few  of  the  lymph-corpuscles 
have  been  washed  out  to  show  its  supporting 
meshwork  of  retiform  tissue  and  its  capillary 
blood-vessels  (which  have  been  injected,  and 
are  dark  in  the  figure);  b,  b,  lymph-path,  of 
which  the  retiform  tissue  is  represented  only 
at  c,  c.  x  300.  (Kolliker.) 

lymphoid   tissue ;    this   occupies 

the  central  part  of  each  alveolus ;  but  at  the  periphery,  surrounding 
the  central  portion  and  immediately  next  the  capsule  and  trabeculse,  is 
a  more  open  meshwork  of  retiform  tissue  constituting  the  lymph-path, 
and  containing  but  few  lymph-corpuscles.  At  the  inner  part  of  the 
alveolus,  the  central  mass  divides  into  two  or  more  smaller  rounded 
or  cord-like  masses  which,  joining  with  those  from  the  other  alveoli, 
form  a  much  closer  arrangement  than  in  the  cortex ;  spaces  (fig.  274  b), 
are  left  within  those  anastomosing  cords,  in  which  are  found  portions 
of  the  trabecular  meshwork  and  the  continuation  of  the  lymph-path. 


381  LYMPH   AND   LYMPHATIC    GLANDS  [CH.  XXIII. 

The  lymph  enters  the  gland  by  several  afferent  vessels,  which 
pierce  the  capsule  and  open  into  the  lymph-path ;  at  the  same  time 
they  lay  aside  all  their  coats  except  the  endothelial  lining,  which  is 
continuous  with  the  lining  of  the  lymph-path.  The  efferent  vessels 
begin  in  the  medullary  part  of  th©  gland,  and  are  continuous  with 
the  lymph-path  here  as  the  afferent  vessels  are  with  the  cortical 
portion. 

The  efferent  vessels  leave  the  gland  at  the  hilus,  and  either  at 
once,  or  very  soon  after,  join  together  to  form  a  single  vessel. 

Blood-vessels  which  enter  and  leave  the  gland  at  the  hilus  are 
freely  distributed  to  the  trabecular  and  lymphoid  tissues. 

The  Lymph  Flow. 

The  flow  of  the  lymph  towards  the  point  of  its  discharge  into  the 
veins  is  brought  about  by  several  agencies.  With  the  help  of  the 
valvular  mechanism  all  occasional  pressure  on  the  exterior  of  the 
lymphatic  and  lacteal  vessels  propels  the  lymph  onward ;  thus 
muscular  and  other  external  pressure  accelerates  the  flow  of  the 
lymph  as  it  does  that  of  the  blood  in  the  veins.  The  action  of  the 
muscular  fibres  of  the  small  intestine,  and  the  layer  of  unstriped 
muscle  present  in  each  intestinal  villus,  assist  in  propelling  the  chyle ; 
in  the  small  intestine  of  many  animals  the  chyle  has  been  seen 
moving  with  intermittent  propulsions  that  correspond  with  the  peri- 
staltic movements  of  the  intestine.  For  the  general  propulsion  of 
the  lymph  and  chyle,  it  is  probable  that,  in  addition  to  external 
pressure,  some  of  the  force  is  derived  from  the  contractility  of  the 
vessel's  own  walls.  The  respiratory  movements,  also,  favour  the 
current  of  lymph  through  the  thoracic  duct  as  they  do  the  current 
of  blood  in  the  thoracic  veins. 

Lymph-Hearts. — In  amphibia,  reptiles  and  some  birds,  an  important  auxiliary 
to  the  movement  of  the  lymph  and  chyle  is  supplied  in  certain  muscular  sacs,  named 
lymph-hearts,  and  it  has  been  shown  that  the  caudal  heart  of  the  eel  is  a  lymph- 
heart  also.  The  number  and  positions  of  these  organs  vary.  In  frogs  and  toads, 
there  are  usually  four,  two  anterior  and  two  posterior.  Into  each  of  these  cavities 
several  lymphatics  open,  the  orifices  of  the  vessels  being  guarded  by  valves,  which 
prevent  the  retrograde  passage  of  the  lymph.  From  each  heart  a  single  vessel 
proceeds,  and  conveys  the  lymph  directly  into  the  venous  system.  Blood  is  pre- 
vented from  passing  into  the  lymphatic  heart  by  a  valve  at  its  orifice. 

The  muscular  coat  of  these  hearts  is  of  variable  thickness  ;  in  some  cases  it  can 
only  be  discovered  by  means  of  the  microscope  ;  but  in  every  case  it  is  composed  of 
striped  fibres.  The  contractions  of  the  hearts  are  rhythmical,  occurring  about 
sixty  times  in  a  minute.  The  pulsations  of  the  cervical  pair  are  not  always 
synchronous  with  those  of  the  pair  in  the  ischiatic  region,  and  even  the  correspond- 
ing sacs  of  opposite  sides  are  not  always  synchronous  in  their  action. 

Unlike  the  contractions  of  the  blood-heart,  those  of  the  lymph-heart  appear  to 
be  directly  dependent  upofi  a  certain  limited  portion  of  the  spinal  cord.  For 
Volkmann  found  that  so  long  as  the  portion  of  spinal  cord  corresponding  to 
the  third  vertebra  of  the  frog  was  uninjured,  the  cervical  pair  of  lymph-hearts. 


CH.  XXIII.]  FORMATION    OF   LYMPH  319 

continued  pulsating  after  all  the  rest  of  the  spinal  cord  and  the  brain  were  destroyed  ; 
while  destruction  of  this  portion,  even  though  all  other  parts  of  the  nervous  centres 
were  uninjured,  instantly  arrested  the  hearts'  movements.  The  posterior,  or 
ischiatic,  pair  of  lymph-hearts  were  found  to  be  governed,  in  like  manner,  by  the 
portion  of  the  spinal  cord  corresponding  to  the  eighth  vertebra.  Division  of  the 
posterior  spinal  roots  did  not  arrest  the  movements ;  but  division  of  the  anterior 
roots  caused  them  to  cease  at  once. 

Jnnervation  of  the  Thoracic  Duct. — By  determining  the  rate  of  outflow  of  a 
fluid  at  constant  pressure  passing  through  the  thoracic  duct,  Camus  and  Gley  have 
obtained  evidence  of  the  presence  of  nerves,  causing  both  dilatation  and  constric- 
tion of  the  duct.  These  are  contained  in  the  sympathetic  chain  below  the  first 
thoracic  ganglion.  The  effect  of  stimulation  is  principally  dilatation. 

Relation  of  Lymph  and  Blood. 

The  volume  of  blood  in  the  body  remains  remarkably  constant. 
If  the  amount  is  increased  by  injection  of  fluids,  at  first  its  specific 
gravity  is  lessened,  but  in  a  short  time,  often  in  a  few  minutes,  it 
returns  to  the  normal.  The  excess  of  fluid  is  got  rid  of  in  two  ways : 
(1)  by  the  kidneys,  which  secrete  profusely ;  and  (2)  by  the  tissues, 
which  become  more  watery  in  consequence.  After  the  renal  arteries 
are  ligatured,  and  the  kidney  is  consequently  thrown  out  of  action, 
the  excess  of  water  passes  only  into  the  tissues. 

On  the  other  hand,  a  deficiency  of  blood  (for  instance,  after 
hemorrhage)  is  soon  remedied  by  a  transfer  of  water  from  the 
tissues  to  the  blood  through  the  intermediation  of  the  lymph. 

In  severe  haemorrhage  life  has  often  been  saved  by  transfusion 
of  blood  from  another  person.  The  transfer  of  the  blood  of  another 
animal  to  the  human  vascular  system  is  usually  dangerous,  especi- 
ally if  the  blood  has  been  defibrinated,  for  the  serum  of  one  animal 
is  usually  poisonous  to  another,  producing  various  changes,  of  which 
a  breakdown  of  the  corpuscles  (haemolysis)  is  the  most  constant 
sign.  It  is,  however,  quite  unnecessary  to  use  blood  at  all  for  this 
purpose;  saline  (preferably  Binger's)  solution  should  be  used 
instead. 

Formation  of  Lymph. 

Carl  Ludwig  taught  that  the  lymph  flow  is  conditioned  by  two 
factors:  first,  differences  in  the  pressure  of  the  blood  in  the  capillaries 
and  of  the  fluid  in  the  tissue  spaces,  giving  rise  to  a,  filtration  of  fluid 
through  the  capillary  walls;  and  secondly,  chemical  differences 
between  these  two  fluids,  setting  up  osmotic  interchanges  through  the 
wall  of  the  blood-vessel.  (See  further,  next  chapter.) 

If  the  lymph  is  produced  by  a  simple  act  of  filtration,  then  the 
amount  of  lymph  must  rise  and  sink  with  the  value  of  D — d\  D 
representing  the  capillary  blood-pressure,  and  d  the  pressure  in  the 
tissue  spaces. 

In  support  of  this  mechanical  theory,  various  workers  in  Ludwig's 


320  LYMPH   AND   LYMPHATIC    GLANDS  [CH.  XXIII. 

laboratory  showed  that  increased  capillary  pressure  due  to  obstruction 
of  the  venous  outflow  increases  the  amount  of  lymph  formed ;  and 
that  diminution  of  the  pressure  in  the  lymph  spaces,  by  squeezing 
out  the  lymph  previously  contained  in  them,  leads  to  an  increase  in 
the  transudation. 

On  the  other  hand,  there  were  some  facts  which  could  not  be  well 
explained  by  the  nitration  theory,  among  which  may  be  mentioned 
the  action  of  curare  in  causing  an  increase  of  lymph  flow. 

Heidenhain  was  the  first  to  fully  recognise  that  the  laws  of 
filtration  and  osmosis  as  applied  to  dead  membranes  may  be  con- 
siderably modified  when  the  membranes  are  composed  of  living  cells  ; 
and  he  considered  that  the  formation  of  lymph  is  due  to  the  selective 
or  secretory  activity  of  the  endothelial  walls  of  the  capillaries.  This 
so-called  vital  action  of  the  endothelial  cells  is  seen  in  the  fact  that 
after  the  injection  of  sugar  into  the  blood,  in  a  short  time  the  per- 
centage of  sugar  in  the  lymph  becomes  higher  than  that  in  the 
blood.  There  must,  therefore,  be  some  activity  of  the  endothelial 
cells  in  picking  out  the  sugar  from  the  blood  and  passing  it  on  to 
the  lymph.  The  excess  of  chlorides  in  lymph  is  also  in  favour  of 
the  same  view. 

Heidenhain  was  the  inventor  of  the  term  lymphagogues  (literally, 
lymph  drivers).  These  are  substances  like  curare,  which  have  a 
specific  action  in  causing  an  increased  lymph  flow.  Heidenhain 
considered  that  the  majority  of  these  act  by  stimulating  the  endo- 
thelial cells  to  activity.  This  conclusion,  however,  has  been  subjected 
to  much  criticism.  In  this  country  the  question  has  been  taken  up 
by  Starling,  who  has  shown  that  the  influence  of  vital  action  is 
not  so  marked  as  Heidenhain  supposed  it  to  be,  but  that  most  of 
the  phenomena  in  connection  with  lymph  formation  can  be  explained 
by  the  simpler  mechanical  theory.  Starling  considers  that  the 
amount  of  lymph  produced  in  any  part  depends  on  two  factors : — 

1.  The  pressure  at  which  the  blood  is  flowing  through  the  capil- 
laries.    Heidenhain  took  the  arterial  pressure  in  his  experiments  as 
the  measure   of   the  capillary  pressure;   Starling  points  out,  very 
justly,  that  this  is  incorrect,  as  there  is  between  the  arteries  and  the 
capillaries  the  unknown  peripheral  resistance  in  the  arterioles. 

2.  The  permeability  of  the  capillary  wall.     This  varies  enormously 
in  different  regions;  it  is  greatest  in  the  liver,  so  that  an  intra- 
capillary  pressure  which  would  cause  lymph  to  flow  here  is  without 
effect  on  the  production  of  lymph  in  the  limbs.     Liver  lymph  is  also 
richer  in  protein  than  lymph  from  the  limbs. 

The  flow  of  lymph  may  therefore  be  increased  in  two  ways : — 
1.  By  increasing  the  intracapillary  pressure.     This  may  be  done 
locally  by  ligaturing  the  veins  of  an  organ ;  or  generally  by  injecting 
a  large  amount  of  fluid  into  the  circulation,  or  by  the  injection  of 


CH.  XXIII.]  LYMPHAGOGUES  321 

such  substances  as  sugar  and  salt  (Heidenhain's  second  class  of 
lymphagogues)  into  the  blood.  These  attract  water  from  the  tissues 
into  the  blood,  and  thus  increase  the  volume  of  the  circulating  fluid 
and  raise  the  intracapillary  pressure. 

2.  By  increasing  the  permeability  of  the  capillary  wall  by  injuring 
its  vitality.  This  may  be  done  locally  by  scalding  a  part;  or 
generally,  by  injecting  certain  poisonous  substances,  such  as  peptone, 
leech  extract,  decoction  of  mussels,  etc.  (Heidenhain's  first  class  of 
lymphagogues).  These  act  chiefly  on  the  liver  capillaries;  curare 
acts  chiefly  on  the  limb  capillaries.  There  is  no  doubt  that  in 
pathological  conditions  which  lead  to  the  production  of  a  great 
increase  of  lymph  (dropsy)  this  second  factor  is  the  more  important 
of  the  two ;  the  increased  permeability  of  the  capillaries  may  be  the 
result  of  malnutrition,  or  due  to  the  action  of  poisons  produced 
by  the  disease. 

In  reference  to  the  action  of  the  endothelial  cells,  it  is  necessary 
to  recognise  that  they  are  alive,  and  are  therefore  capable  of  exerting 
a  selective  action  which  may  mask  or  counteract  or  assist  purely 
physical  processes.  If  the  action  of  poisons  was  simply  to  injure  the 
vessel  wall  and  increase  its  permeability,  the  amount  of  lymph 
should  be  proportional  to  the  intensity  of  the  injury;  but  this 
is  not  always  found  to  be  the  case.  Lymph  formation  is  doubtless 
mainly  influenced  by  the  physical  conditions  present,  for  the 
action  of  such  thin  cells  as  those  of  the  capillary  wall  cannot  be 
sufficiently  great  to  entirely  counteract  these  conditions;  at  the 
same  time  it  is  impossible  to  deny  that  there  is  some  such  action 
as  may  be  described  by  the  terms  "  selective "  or  "  secretory."  The 
question  is  closely  related  to  that  of  absorption  from  the  alimen- 
tary canal,  and  we  shall  find  in  studying  that  subject  that  there 
has  been  a  similar  difference  of  opinion,  but  that  recent  research  has 
confirmed  the  theory  of  selective  activity  of  the  absorptive  epithelium. 

Dr  Martin  H.  Fischer  has  advanced  a  new  theory  of  dropsy  or 
oedema  within  the  last  few  years.  He  believes  that  circulatory 
conditions  are  of  minor  importance,  but  that  the  main  factor  leading 
to  transudation  of  water  into  the  tissues  is  to  be  found  in  the  tissues 
themselves.  He  finds  that  colloids  imbibe  more  water  from  an  acid 
solution  than  under  other  conditions.  He  therefore  believes  that  it 
is  the  accumulation  of  acid  products  (such  as  lactic  acid)  in  the 
tissues  that  determines  their  increased  affinity  for  water,  and  thus 
they  attract  it  out  of  the  blood.  The  theory  has  met  with  much 
adverse  criticism,  and  it  is  too  early  at  present  to  state  whether 
Fischer  or  his  critics  are  correct. 


CHAPTER  XXIV 

PHYSICAL   CHEMISTRY    AND   ITS   BEARING   ON    PHYSIOLOGICAL 
PROBLEMS 

THE  investigations  of  physical  chemists  during  recent  years  have  given  us  new 
conceptions  of  the  nature  of  solutions,  and  these  have  important  bearings  on  the 
explanation  of  osmotic  phenomena,  and  so  are  interesting  to  the  physiologist. 

Water  is  the  fluid  in  which  soluble  materials  are  usually  dissolved,  and  at 
ordinary  temperatures  it  is  a  fluid  the  molecules  of  which  are  in  constant  movement ; 
the  hotter  the  water  the  more  active  are  the  movements  of  its  molecules,  until  when 
at  last  it  is  converted  into  steam,  the  molecular  movements  become  much  more 
energetic.  Perfectly  pure  water  consists  of  molecules  with  the  formula  H2O,  and 
these  molecules  undergo  practically  no  dissociation  into  their  constituent  ions,  and 
it  is  for  this  reason  that  pure  water  is  not  a  conductor  of  electricity. 

If  a  substance  like  sugar  is  dissolved  in  the  water,  the  solution  still  remains 
incapable  of  conducting  an  electrical  current.  The  sugar  molecules  in  solution  are 
still  sugar  molecules  ;  they  do  not  undergo  dissociation. 

But  if  a  substance  like  salt  is  dissolved  in  the  water,  the  solution  is  then  capable 
of  conducting  electrical  currents,  and  the  same  is  true  for  most  acids,  bases,  and  salts. 
These  substances  do  undergo  dissociation,  and  the  simpler  materials  into  which 
they  are  broken  up  in  the  water  are  called  ions.  Thus,  if  sodium  chloride  is  dissolved 
in  water  a  certain  number  of  its  molecules  become  dissociated  into  sodium  ions, 
which  are  charged  with  positive  electricity,  and  chlorine  ions,  which  are  charged 
with  negative  electricity.  Similarly  a  solution  of  hydrochloric  acid  in  water  con- 
tains free  hydrogen  ions  and  free  chlorine  ions.  Sulphuric  acid  is  decomposed  into 
hydrogen  ions  and  ions  of  SO4.  The  term  ion  is  thus  not  equivalent  to  atom,  for 
an  ion  may  be  a  group  of  atoms,  such  as  SO4,  in  the  example  just  given. 

Further,  in  the  case  of  hydrochloric  acid,  the  negative  charge  of  the  chlorine 
ion  is  equal  to  the  positive  charge  of  the  hydrogen  ion ;  but  in  the  case  of  the 
sulphuric  acid,  the  negative  charge  of  the  SO4  ion  is  equal  to  the  positive  charge  of 
two  hydrogen  ions.  We  can  thus  speak  of  monovalent,  divalent,  trivalent,  etc. ,  ions. 

Ions  positively  charged  are  called  kat-ions  because  they  move  towards  the  kathode 
or  negative  pole  ;  those  which  are  negatively  charged  are  called  an-ions  because  they 
move  towards  the  anode  or  positive  pole.  The  following  are  some  examples  of  each 
class : — 

Kat-ions.    Monovalent :— H,  Na,  K,  NH4,  etc. 

Divalent :— Ca,  Ba,  Fe  (in  ferrous  salts),  etc. 
Trivalent :— Al,  Bi,  Sb,  Fe  (in  ferric  salts),  etc. 

An  ions.       Monovalent :— Cl,  Br,  I,  OH,  NO3,  etc. 
Divalent :— S,  Se,  SO4,  etc. 

Roughly  speaking,  the  greater  the  dilution  the  more  nearly  complete  is  the 
dissociation,  and  in  a  very  dilute  solution  of  such  a  substance  as  sodium  chloride 
we  may  consider  that  the  number  of  ions  is  double  the  number  of  molecules  of  the 
salt  present. 

The  ions  liberated  by  the  act  of  dissociation  are,  as  we  have  seen,  charged  with 
electricity,  and  when  an  electrical  current  is  led  into  such  a  solution,  it  is  conducted 


CH.  XXIV.]  OSMOTIC    PHENOMENA  323 

through  the  solution  by  the  movement  of  the  ions.  Substances  which  exhibit  the 
property  of  dissociation  are  known  as  electrolytes. 

The  liquids  of  the  body  contain  electrolytes  in  solution,  and  it  is  owing  to  this 
fact  that  they  are  able  to  conduct  electrical  currents. 

This  conception  of  electrolytes  which  we  owe  to  Arrhenius  is  extremely  impor- 
tant in  view  of  the  question  of  osmotic  pressure,  because  the  act  of  dissociation 
increases  the  number  of  particles  moving  in  the  solution,  and  so  increases  the 
osmotic  pressure,  for  in  this  relation  an  ion  plays  the  same  part  as  a  molecule. 

Another  physiological  aspect  of  the  subject  is  seen  in  a  study  of  the  actions  of 
mineral  salts  in  solution  on  living  organisms  and  parts  of  organisms.  Many  years 
ago  Ringer  showed  that  contractile  tissues  (heart,  cilia,  etc.)  continue  to  manifest 
their  activity  in  certain  saline  solutions. 

Loeb  and  his  fellow-workers  have  confirmed  these  statements,  but  interpret  them 
now  as  ionic  action.  Contractile  tissues  will  not  contract  in  pure  solutions  of  non- 
electrolytes  (such  as  sugar,  urea,  albumin).  But  different  contractile  tissues  differ 
in  the  nature  of  the  ions  which  are  most  favourable  stimuli.  Thus  cardiac  muscle, 
cilia,  amoeboid  movement,  karyokinesis,  cell  division,  are  all  alike  in  requiring  a 
proper  adjustment  of  ions  in  their  surroundings  if  they  are  to  continue  to  act,  but 
the  proportions  must  be  different  in  individual  cases. 

Loeb  at  one  time  considered  that  the  process  of  fertilisation  was  mainly  ionic 
action,  but  since  then  he  has  modified  his  views  ;  the  action  of  ions  is  only  one  of 
many  factors.  Howell's  work,  however,  on  the  action  of  ions  in  the  causation 
of  the  heart-beat  (see  p.  261)  may  be  taken  as  one  of  the  best-proved  instances 
of  the  importance  of  this  branch  of  study. 

Gramme-molecular  Solutions. — From  the  point  of  view  of  osmotic  pressure  a 
convenient  unit  is  the  gramme-molecule.  A  gramme-molecule  of  any  substance  is 
the  quantity  in  grammes  of  that  substance  equal  to  its  molecular  weight.  A 
gramme-molecular  solution  is  one  which  contains  a  gramme-molecule  of  the  sub- 
stance per  litre.  Thus  a  gramme-molecular  solution  of  sodium  chloride  is  one  which 
contains  58'46  grammes  of  sodium  chloride  CNa  =  23'00:  01  =  35*46)  in  a  litre.  A 
gramme-molecular  solution  of  grape  sugar  (C6H]2O6)  is  one  which  contains  180 
grammes  of  grape  sugar  in  a  litre.  A  gramme-molecule  of  hydrogen  (H2)  is  2 
grammes  by  weight  of  hydrogen,  and  if  this  was  compressed  to  the  volume  of  a 
litre,  it  would  be  comparable  to  a  gramme-molecular  solution.  It  therefore  follows 
that  a  litre  containing  2  grammes  of  hydrogen  contains  the  same  number  of 
molecules  of  hydrogen  in  it  as  a  litre  of  a  solution  containing  58 '46  grammes  of 
sodium  chloride,  or  one  containing  180  grammes  of  grape  sugar,  has  in  it  of  salt 
or  sugar  molecules  respectively.  To  put  it  another  way,  the  heavier  the  weight  of 
a  molecule  of  any  substance,  the  more  of  that  substance  must  be  dissolved  in  the 
litre  to  obtain  its  gramme-molecular  solution.  Or  still  another  way  :  if  solutions  of 
various  substances  are  made  all  of  the  same  strength  per  cent. ,  the  solutions  of  the 
materials  of  small  molecular  weight  will  contain  more  molecules  of  those  materials 
than  the  solutions  of  the  materials  which  have  heavy  molecules.  We  shall  see  that 
the  calculation  of  osmotic  pressure  depends  upon  these  facts. 

Diffusion,  Dialysis,  Osmosis. — If  two  gases  are  brought  together  within  a 
closed  space,  a  homogeneous  mixture  of  the  two  is  soon  obtained.  This  is  due 
to  the  movements  of  the  gaseous  molecules  within  the  confining  space,  and  the 
process  is  called  diffusion.  In  a  similar  way  diffusion  will  effect  in  time  a  homo- 
geneous mixture  of  two  liquids  or  solutions.  If  water  is  carefully  poured  on  to  the 
surface  of  a  solution  of  salt,  the  salt  or  its  ions  will  soon  be  equally  distributed 
throughout  the  whole.  If  a  solution  of  albumin  or  any  other  colloidal  substance  is 
used  instead  of  salt  in  the  experiment,  diffusion  will  be  found  to  occur  much  more 
slowly.  If,  instead  of  pouring  the  water  on  to  the  surface  of  a  solution  of  salt  or 
sugar,  the  two  are  separated  by  a  membrane  made  of  such  a  material  as  parchment 
paper,  a  similar  diffusion  will  occur,  though  more  slowly  than  in  cases  where  the 
membrane  is  absent.  In  time,  the  water  on  each  side  of  the  membrane  will  contain 
the  same  quantity  of  sugar  or  salt.  Substances  which  pass  through  such  membranes 
are  called  crystalloids.  Substances  which  have  such  large  molecules  (starch,  pro- 
tein, etc.)  that  they  will  not  pass  through  such  membranes  are  called  colloids. 
Diffusion  of  substances  in  solution  which  have  to  deal  with  an  intervening  membrane 


324 


PHYSICAL   CHEMISTRY 


[CH.  XXIV. 


FIG. 


M 


is  usually  called  dialysis.  The  process  of  filtration  (i.  e. ,  the  passage  of  materials 
through  the  pores  of  a  membrane  under  the  influence  of  mechanical  pressure)  may 
be  excluded  in  such  experiments  by  placing  the  membrane 
(M)  vertically  as  shown  in  the  diagram  (fig.  275),  and  the 
two  fluids  A  and  B  on  each  side  of  it.  Diffusion  through 
a  membrane  is  not  limited  to  the  molecules  of  water,  but  it 
may  occur  also  in  the  molecules  of  certain  substances  dis- 
solved in  the  water.  But  very  few  or  no  membranes  are 
equally  permeable  to  water  and  to  molecules  of  the  sub- 
stances dissolved  in  the  water.  If  in  the  accompanying 
diagram  the  compartment  A  is  filled  with  pure  water,  and 
B  with  a  sodium  chloride  solution,  the  liquids  in  the  two 
compartments  will  ultimately  be  found  to  be  equal  in  bulk 
as  they  were  at  the  start,  and  each  will  be  a  solution  of  salt 
of  half  the  strength  of  that  originally  in  the  compartment 
B.  But  at  first  the  volume  of  the  liquid  in  compartment  B 
increases,  because  more  water  molecules  pass  into  it  from 

A  than  salt  molecules  pass  from  B  to  A.  The  term  osmosis  is  generally  limited 
to  the  stream  of  water  molecules  passing  through  a  membrane,  while  the  term 
dialysis  is  applied  to  the  passage  of  the  molecules  in  solution  in  the  water.  The 
osmotic  stream  of  water  is  especially  important,  and  in  connection  with  this  it  is 

necessary  to  explain  the  term  osmotic  pressure.  At 
first,  then,  osmosis  (the  diffusion  of  water)  is  more 
rapid  than  the  dialysis  (the  diffusion  of  the  salt 
molecules  or  ions).  The  older  explanation  of  this 
was  that  salt  attracted  the  water,  but  we  now 
express  the  fact  differently  by  saying  that  the  salt  in 
solution  exerts  a  certain  osmotic  pressure  :  the  result 
of  the  osmotic  pressure  is  that  more  water  flows  from 
the  water  side  to  the  side  of  the  solution  than  in  the 
contrary  direction.  The  osmotic  pressure  varies  with 
the  amount  of  substance  in  solution,  and  is  also 
altered  by  variations  of  temperature  occurring  more 
rapidly  at  high  than  at  low  temperatures. 

If  we  imagine  two  masses  of  water  separated  by 
a  permeable  membrane,  as  many  water  molecules 
will  pass  through  from  one  side  as  from  the  other, 
and  so  the  volumes  of  the  two  masses  of  water  will 
remain  unchanged.  If  now  we  imagine  the  mem- 
brane M  is  not  permeable  except  to  water,  and  the 
compartment  A  contains  water,  and  the  compart- 
ment B  contains  a  solution  of  salt  or  sugar  ;  under 
these  circumstances  water  will  pass  through  into  B, 
and  the  volume  of  B  will  increase  in  proportion  to 
the  osmotic  pressure  of  the  sugar  or  salt  in  solution 
in  B,  but  no  molecules  of  sugar  or  salt  can  get  through 
into  A  from  B,  so  the  volume  of  fluid  in  A  will  con- 
tinue to  decrease,  until  at  last  a  limit  is  reached.  The 
determination  of  this  limit,  as  measured  by  the  height 
of  a  column  of  fluid  or  mercury  which  it  will  support, 
will  give  us  a  measurement  of  the  osmotic  pressure. 

If  a  bladder  containing  strong  salt  solution  is 
placed  in  a  vessel  of  distilled  water,  water  passes  into 
the  bladder  by  osmosis,  so  that  the  bladder  is  swollen, 
and  a  manometer  connected  with  its  interior  will  show 
a  rise  of  pressure  (osmotic  pressure).  But  the  total 
rise  of  pressure  cannot  be  measured  in  this  way  for 
two  reasons  :  (1)  because  the  salt  diffuses  out  as  the 

water  diffuses  in ;  and  (2)  because  the  membrane  of  the  bladder  leaks ;  that  is, 
permits  of  filtration  when  the  pressure  within  it  has  attained  a  certain  height. 


B 


FIG.  27(5. — A,  outer  vessel,  con- 
taining distilled  water ;  B, 
inner  semi-permeable  vessel, 
containing  1  per  cent,  salt 
solution  ;  M,  mercurial 
manometer.  (After  Star- 
ling.) 


CH.  XXIY.]  OSMOTIC   PRESSURE  325 

It  is  therefore  necessary  to  use  a  membrane  which  will  not  allow  salt  to  pass 
out  either  by  dialysis  or  filtration,  though  it  will  let  the  water  pass  in.  Such 
membranes  are  called  semi-permeable  membranes,  and  one  of  the  best  of  these  is 
ferrocyanide  of  copper.  This  may  be  made  by  taking  a  cell  of  porous  earthenware 
and  washing  it  out  first  with  copper  sulphate  and  then  with  potassium  ferrocyanide. 
An  insoluble  precipitate  of  copper  ferrocyanide  is  thus  deposited  in  the  pores  of  the 
earthenware. 

If  such  a  cell  is  arranged  as  in  fig.  276,  and  filled  with  a  1  per  cent,  solution  of 
sodium  chloride,  water  diffuses  in,  till  the  pressure  registered  by  the  manometer 
reaches  the  enormous  height  of  5000  mm.  of  mercury.  If  the  pressure  in  the  cell  is 
increased  beyond  this  artificially,  water  will  be  pressed  through  the  semi-permeable 
walls  of  the  cell  and  the  solution  will  become  more  concentrated. 

In  other  words,  in  order  to  make  a  solution  of  sodium  chloride  of  greater 
concentration  than  1  per  cent.,  a  pressure  greater  than  5000  mm.  of  mercury  must 
be  employed.  The  osmotic  pressure  exerted  by  a  2  per  cent,  solution  would  be 
twice  as  great. 

Though  it  is  theoretically  possible  to  measure  osmotic  pressure  by  a  manometer 
in  this  direct  way,  practically  it  is  hardly  ever  done,  and  some  of  the  indirect 
methods  of  measurement  described  later  are  used  instead.  The  reason  for  this  is 
that  it  has  been  found  difficult  to  construct  a  membrane  which  is  absolutely  semi- 
permeable  ;  they  are  nearly  all  permeable  in  some  degree  to  the  molecules  of  the 
dissolved  crystalloid.  In  course  of  time,  therefore,  the  dissolved  crystalloid  will 
be  equally  distributed  on  both  sides  of  the  membrane,  and  osmosis  of  water  will 
cease  to  be  apparent,  since  it  will  be  equal  in  both  directions. 

Many  explanations  of  the  nature  of  osmotic  pressure  have  been  brought 
forward,  but  none  is  perfectly  satisfactory.  The  following  simple  explanation  is 
perhaps  the  best,  and  may  be  rendered  most  intelligible  by  an  illustration. 
Suppose  we  have  a  solution  of  sugar  separated  by  a  semi-permeable  membrane 
from  water ;  that  is,  the  membrane  is  permeable  to  water  molecules,  but  not  to 
sugar  molecules.  The  streams  of  water  from  the  two  sides  will  then  be  unequal ; 
on  one  side  we  have  water  molecules  striking  against  the  membrane  in  what  we 
may  call  normal  numbers,  while  on  the  other  side  both  water  molecules  and  sugar 
molecules  are  striking  against  it.  On  this  side,  therefore,  the  sugar  molecules 
take  up  a  certain  amount  of  room,  and  do  not  allow  the  water  molecules  to  get 
to  the  membrane ;  the  membrane  is,  as  it  were,  screened  against  the  water  by 
the  sugar,  therefore  fewer  water  molecules  will  get  through  from  the  screened  to 
the  unscreened  side  than  vice  versa.  This  comes  to  the  same  thing  as  saying  that 
the  osmotic  stream  of  water  is  greater  from  the  unscreened  water  side  to  the 
screened  sugar  side  than  it  is  in  the  reverse  direction.  The  more  sugar  molecules 
that  are  present,  the  greater  will  be  their  screening  action,  and  thus  we  see  that 
the  osmotic  pressure  is  proportional  to  the  number  of  sugar  molecules  in  the 
solution,  that  is,  to  the  concentration  of  the  solution. 

Osmotic  pressure  is,  in  fact,  equal  to  that  which  the  dissolved  substance  would 
exert  if  it  occupied  the  same  space  in  the  form  of  a  gas  (Van't  HofTs  hypothesis). 
The  nature  of  the  substance  makes  no  difference ;  it  is  only  the  number  of  mole- 
cules which  causes  osmotic  pressure  to  vary.  The  osmotic  pressure,  however,  of 
substances  like  sodium  chloride,  which  are  electrolytes,  is  greater  than  what  one 
would  expect  from  the  number  of  molecules  present.  This  is  because  the  molecules 
in  solution  are  split  into  their  constituent  ions,  and  an  ion  plays  the  same  part  as 
a  molecule,  in  questions  of  osmotic  pressure.  In  dilute  solutions  of  sodium  chloride 
ionisation  is  more  complete,  and  as  the  total  number  of  ions  is  then  nearly  double 
the  number  of  original  molecules,  the  osmotic  pressure  is  nearly  double  what  would 
have  been  calculated  from  the  number  of  molecules. 

The  analogy  between  osmotic  pressure  and  the  pressure  of  gases  is  very  com- 
plete, as  may  be  seen  from  the  following  statements  : — 

1.  At  a  constant  temperature  osmotic  pressure  is  proportional  to  the  concentra- 
tion of  the  solution  (Boyle-Mariotte's  law  for  gases). 

2.  With  constant  concentration,  the  osmotic  pressure  rises  with  and  is  propor- 
tional to  the  temperature  (Gay-Lussac's  law  for  gases). 

3.  The  osmotic  pressure  of  a  solution  of  different  substances  is  equal  to  the  sum 


326  PHYSICAL  CHEMISTRY  [CH.  XXIV. 

of  the  pressures  which  the  individual  substances  would  exert  if  they  were  alone  in 
the  solution  (Henry-Dalton  law  for  partial  pressure  of  gases). 

4.  The  osmotic  pressure  is  independent  of  the  nature  of  the  substance  in 
solution,  and  depends  only  on  the  number  of  molecules  or  ions  in  solution 
(Avogadro's  law  for  gases). 

Calculation  of  Osmotic  Pressure. — We  may  best  illustrate  this  by  an  example, 
and  to  simplify  matters  we  will  take  an  example  in  the  case  of  a  non-electrolyte 
such  as  sugar.  We  shall  then  not  have  to  take  into  account  any  electrolytic  dissocia- 
tion of  the  molecules  into  ions.  We  will  suppose  we  want  to  calculate  the  osmotic 
pressure  of  a  1  per  cent,  solution  of  cane  sugar. 

One  gramme  of  hydrogen  at  atmospheric  pressure  and  0°  C.  occupies  a  volume 
of  11 '2  litres;  two  grammes  of  hydrogen  will  therefore  occupy  a  volume  of  22 '4 
litres.  A  gramme-molecule  of  hydrogen — that  is,  2  grammes  of  hydrogen — when 
brought  to  the  volume  of  1  litre,  will  exert  a  gas  pressure  equal  to  that  of  22 '4  litres 
compressed  to  1  litre — that  is,  a  pressure  of  22  -4  atmospheres.  A  gramme-mole- 
cular solution  of  cane  sugar,  since  it  contains  the  same  number  of  molecules  in  a 
litre,  must  therefore  exert  an  osmotic  pressure  of  22*4  atmospheres  also.  A 
gramme-molecular  solution  of  cane  sugar  (C^H^On)  contains  342  grammes  of  cane 
sugar  in  a  litre  of  water.  A  1  per  cent,  solution  of  cane  sugar  contains  only  10 
grammes  of  cane  sugar  in  a  litre ;  hence  the  osmotic  pressure  of  a  1  per  cent. 

solution  of  cane  sugar  is  — —     x22'4   atmospheres,   or   0'65   of  an   atmosphere, 

which  in  terms  of  a  column  of  mercury  =  760  x  0'65  =  494  mm. 

It  would  not  be  possible  to  make  such  a  calculation  in  the  case  of  an  electro- 
lyte, because  we  should  not  know  how  many  molecules  had  been  ionised.  In  the 
liquids  of  the  body,  both  electrolytes  and  non-electrolytes  are  present,  and  so  a 
calculation  is  here  also  impossible. 

We  have  seen  that  for  such  liquids  the  osmotic  pressure  is  seldom  directly 
measured  by  a  manometer,  because  of  the  difficulty  in  obtaining  perfect  semi- 
permeable  membranes ;  we  now  see  that  mere  arithmetic  often  fails  us ;  and  so 
we  come  to  the  question  to  which  we  have  been  so  long  leading  up,  viz.,  how 
osmotic  pressure  is  actually  determined. 

Determination  of  Osmotic  Pressure  by  means  of  the  Freezing-point. — 
This  is  the  method  which  is  almost  universally  employed.  A  very  simple  apparatus 
(Beckmann's  differential  thermometer)  is  all  that  is  necessary.  The  principle  on 
which  the  method  depends  is  the  following  : — The  freezing-point  of  any  substance 
in  solution  in  water  is  lower  than  that  of  water  ;  the  lowering  of  the  freezing-point 
is  proportional  to  the  molecular  concentration  of  the  dissolved  substance,  and  that, 
as  we  have  seen,  is  proportional  to  the  osmotic  pressure. 

When  a  gramme-molecule  of  any  substance  is  dissolved  in  a  litre  of  water,  the 
freezing-point  is  lowered  by  1'87°C. ,  and  the  osmotic  pressure  is,  as  we  have  seen, 
equal  to  22-4  atmospheres,  that  is,  22'4  x  760  -  17,024  mm.  of  mercury. 

We  can,  therefore,  calculate  the  osmotic  pressure  of  any  solution  if  we  know 
the  lowering  of  its  freezing-point  in  degrees  Centigrade  ;  the  lowering  of  the 
freezing-point  is  usually  expressed  by  the  Greek  letter  A. 

Osmotic  pressure  =  -- _-»  x  17,024. 
1  "o/ 

For  example,  a  1  per  cent,  solution  of  sugar  would  freeze  at  -0'052°  C.  ;  its 
osmotic  pressure  is  therefore  1-37'  -4'3  mm.,  a  number  approximately 

equal  to  that  we  obtained  by  calculation. 

Mammalian  blood  serum  gives  A  =  0'o6°  C.  A  0'9  per  cent,  solution  of  sodium 
chloride  has  the  same  A  ;  hence  serum  and  a  0'9  per  cent,  solution  of  common  salt 
have  the  same  osmotic  pressure,  or  are  isotonic.  The  osmotic  pressure  of  blood 

serum  is =-^=f =5000  mm.  of  mercury  approximately,  or  a  pressure  of  nearly 

1  *o/ 

7  atmospheres. 

The  osmotic  pressure  of  solutions  may  also  be  compared  by  observing  their 
effect  on  red  blood-corpuscles,  or  on  vegetable  cells  such  as  those  in  Tradescantia. 


CH.  XXIV.]  OSMOTIC    PKESSUKE  327 

If  the  solution  is  hypertonic*  i.e.*  has  a  greater  osmotic  pressure  than  the  cell  con- 
tents, the  protoplasm  shrinks,  and  loses  water,  or  if  red  corpuscles  are  used,  they 
become  crenated ;  if  the  solution  is  hypotonic,  i.e.,  has  a  smaller  osmotic  pressure 
than  the  material  within  the  cell-wall,  no  shrinking  of  the  protoplasm  in  the 
vegetable  cell  takes  place ;  and  if  red  corpuscles  are  used  they  swell  and  liberate 
their  pigment,  hotonic  solutions,  such  as  physiological  salt  solution,  produce  neither 
of  these  effects,  because  they  have  the  same  molecular  concentration  and  osmotic 
pressure  as  the  material  within  the  cell-wall. 

Physiological  Applications. — It  will  at  once  be  seen  how  important  all  these 
considerations  are  from  the  physiological  standpoint.  In  the  body  we  have  aqueous 
solutions  of  various  substances  separated  from  one  another  by  membranes.  Thus 
we  have  the  endothelial  walls  of  the  capillaries  separating  the  blood  from  the  lymph  ; 
we  have  the  epithelial  walls  of  the  kidney  tubules  separating  the  blood  and  lymph 
from  the  urine ;  we  have  similar  epithelium  in  all  secreting  glands ;  and  we  have 
the  wall  of  the  alimentary  canal  separating  the  digested  food  from  the  blood-vessels 
and  lacteals.  In  such  important  problems,  then,  as  lymph-formation,  the  forma- 
tion of  urine  and  other  excretions  and  secretions,  and  absorption  of  food,  we  have 
to  take  into  account  the  laws  which  regulate  the  movements  both  of  water  and  of 
substances  which  are  held  in  solution  by  the  water.  In  the  body  osmosis  is  not  the 
only  force  at  work,  but  we  have  also  to  consider  filtration,  that  is,  the  forcible 
passage  of  materials  through  membranes,  due  to  differences  of  mechanical  pressure. 
Further  complicating  these  two  processes  we  have  to  take  into  account  another 
force,  namely,  the  secretory  or  selective  activity  of  the  living  cells  of  which  the 
membranes  in  question  are  composed.  This  is  sometimes  called  by  the  name  vital 
action^  which  is  an  unsatisfactory  and  unscientific  expression.  The  laws  which 
regulate  filtration,  inhibition  (or  adsorption),  and  osmosis  are  fairly  well  known  and 
can  be  experimentally  verified.  But  we  have  undoubtedly  some  other  force,  or 
some  other  manifestation  of  force,  in  the  case  of  living  membranes.  It  probably 
is  some  physical  or  chemical  property  of  living  matter  which  has  not  yet  been 
brought  into  line  with  the  known  chemical  and  physical  forces  which  operate  in  the 
inorganic  world.  We  cannot  deny  its  existence,  for  it  sometimes  operates  so  as  to 
neutralise  the  known  forces  of  osmosis  and  filtration. 

The  more  one  studies  the  question  of  lymph-formation,  the  more  convinced  one 
becomes  that  mere  osmosis  and  filtration  will  not  explain  it  entirely.  The  basis  of 
the  action  is  no  doubt  physical,  but  the  living  cells  do  not  behave  like  the  dead 
membrane  of  a  dialyser  ;  they  have  a  selective  action,  picking  out  some  substances 
and  passing  them  through  to  the  lymph,  while  they  reject  others. 

The  question  of  gaseous  interchanges  in  the  lungs  is  another  of  a  similar 
kind.  Some  maintain  that  all  can  be  explained  by  the  laws  of  diffusion  of  gases  ; 
others  have  asserted  that  the  action  is  wholly  or  partly  vital.  We  shall,  however, 
find  that  recent  accurate  work  has  shown  that  the  main  facts  are  explicable  on  a 
physical  basis.  Take  again  the  case  of  absorption.  The  object  of  digestion  is  to 
render  the  food  soluble  and  diffusible ;  it  can  hardly  be  supposed  that  this  is 
useless  ;  the  readily  diffusible  substances  will  pass  more  easily  through  into  the 
blood  and  lymph  :  but  still,  as  Waymouth  Reid  has  shown,  if  the  living  epithelium 
of  the  intestine  is  removed,  absorption  comes  very  nearly  to  a  standstill,  although 
from  the  purely  physical  standpoint  removal  of  the  thick  columnar  epithelium 
would  increase  the  facilities  for  osmosis  and  filtration. 

The  osmotic  pressure  exerted  by  crystalloids  is  very  considerable,  but  their 
ready  diffusibility  limits  their  influence  on  the  flow  of  water  in  the  body.  Thus  if  a 
strong  solution  of  salt  is  injected  into  the  blood,  the  first  effect  will  be  the  setting 
up  of  an  osmotic  stream  from  the  tissues  to  the  blood.  The  salt,  however,  would 
soon  diffuse  out  into  the  tissues,  and  would  now  exert  osmotic  pressure  in  the 
opposite  direction.  Moreover,  both  effects  will  be  but  temporary,  because  excess  of 
salt  is  soon  got  rid  of  by  the  excreting  organs. 

Osmotic  Pressure  of  Proteins. — It  has  been  generally  assumed  that  proteins, 
the  most  abundant  and  important  constituents  of  the  blood,  exert  little  or  no 
osmotic  pressure.  Starling,  however,  has  claimed  that  they  have  a  small  osmotic 
pressure ;  if  this  is  so,  it  is  of  importance,  for  proteins,  unlike  salt,  do  not  diffuse 
readily,  and  their  effect  therefore  remains  as  an  almost  permanent  factor  in  the 


328  PHYSICAL   CHEMISTRY  [CH.  XXIV. 

blood.  Starling  gives  the  osmotic  pressure  of  the  proteins  of  the  blood-plasma  as 
equal  to  30  mm.  of  mercury.  We  should  from  the  theoretical  standpoint  find  it 
difficult  to  imagine  that  a  pure  protein  can  exert  more  than  a  minimal  osmotic 
pressure.  It  is  made  up  of  such  huge  molecules  that,  even  when  the  proteins  are 
present  to  the  extent  of  7  or  8  per  cent. ,  as  they  are  in  blood-plasma,  there  are 
comparatively  few  protein  molecules  present,  and  these  are  in  a  state  of  colloidal 
solution,  not  true  solution.  Still,  by  means  of  this  weak  but  constant  pressure  it  is 
possible  to  explain  the  fact  that  an  isotonic  or  even  a  hypertonic  solution  of  a 
diffusible  crystalloid  may  be  completely  absorbed  from  the  peritoneal  cavity  into 
the  blood. 

The  functional  activity  of  the  tissue  elements  is  accompanied  by  the  breaking 
down  of  their  protein  constituents  into  such  simple  materials  as  urea  (and  its 
precursors)  sulphates  and  phosphates.  These  materials  pass  into  the  lymph,  and 
increase  its  molecular  concentration  and  its  osmotic  pressure  ;  thus  water  is 
attracted  (to  use  the  older  way  of  putting  it)  from  the  blood  to  the  lymph,  and  so 
the  volume  of  the  lymph  rises  and  its  flow  increases.  On  the  other  hand,  as  these 
substances  accumulate  in  the  lymph  they  will  in  time  attain  there  a  greater  concen- 
tration than  in  the  blood,  and  so  they  will  diffuse  towards  the  blood,  by  which  they 
are  carried  to  the  organs  of  excretion. 

But,  again,  we  have  a  difficulty  with  the  proteins  ;  they  are  most  important  for 
the  nutrition  of  the  tissues,  but  they  are  practically  indiffusible.  We  must 
therefore  assume  that  their  presence  in  the  lymph  is  due  to  filtration  from  the  blood. 
The  plasma  in  the  capillaries  is  under  a  somewhat  higher  pressure  than  the  lymph 
in  the  tissues,  and  this  tends  to  squeeze  the  constituents  of  the  blood,  including 
the  proteins,  through  the  capillary  walls.  I  have,  however,  already  indicated  that 
the  question  of  lymph-formation  is  one  of  the  many  physiological  problems  which 
await  solution  by  the  physiologists  of  the  future. 

Waymouth  Reid  finds  that  absolutely  pure  proteins  exert  no  osmotic  pressure  ; 
the  pressure  observed  is  due  to  saline  and  other  materials  from  which  it  is  difficult  to 
disentangle  the  protein.  *  Haemoglobin  is  an  exception  to  this  rule  ;  it  exerts  a  small 
osmotic  pressure  and  forms  a  true  solution  with  water. 

Colloidal  Solutions. — The  study  of  colloids  is  important,  seeing  how  many 
important  physiological  substances  belong  to  this  class  ;  for  instance,  the  proteins, 
starches,  and  soaps.  Their  main  characters  are,  that  they  do  not  pass  the 
membrane  of  a  dialyser,  their  solutions  are  opalescent,  they  crystallise  with 
difficulty  if  at  all,  they  have  a  tendency  to  form  jellies  (as  in  the  case  of  gelatin), 
or  to  coagulate  under  the  influence  of  heat  and  other  agents  (as  in  the  case  of 
most  proteins),  and  they  exert  a  low  osmotic  pressure.  Inorganic  substances 
(e.g.,  several  metals,  and  compounds  such  as  silicic  acid)  may  also  assume  a 
colloidal  condition  ;  these  are  in  an  unstable  physical  condition,  passing  from  the 
"sol*'  (or  soluble)  to  the  "gel"  (or  jelly-like)  condition  under  slight  provocation. 
This  confers  upon  them  their  power  to  act  as  catalysts. 

The  solutions  formed  by  colloidal  materials  are  not  true  solutions,  even 
although  the  highest  powers  of  the  microscope  reveal  no  visible  particles.  Never- 
theless efficient  filters  made  of  gelatin  will  not  allow  these  substances  to  pass 
through  them.  Colloidal  solutions  also  show  what  is  known  as  the  Tyndall 
phenomenon  ;  that  is,  the  particles,  though  invisible,  will  nevertheless  scatter  light, 
just  as  minute  dust  particles  in  the  air  are  lit  up  by  a  beam  of  sunlight.  This 
test  forms  the  basis  of  the  instrument  known  as  the  ultra-microscope.  Such 
observations  show  that  colloidal  solutions  are  really  suspensions  of  extremely 
minute  particles. 

Reaction  Velocity.— Most  reactions  in  Inorganic  Chemistry  take  place 
between  electrolytes  substances  which  are  good  conductors  of  the  electric  current. 
These  may  be  considered  as  reactions  between  ions,  and  Ionic  Reactions  occur  at 

*  Bayliss  has  shown  that  the  saline  constituents  found  in  a  native  protein  are 
not  mechanically  mixed  with  it,  and  are  also  not  in  true  chemical  combination  with 
it,  but  are  in  a  condition  intermediate  between  these  two  extremes,  to  which  the 
term  adsorption  is  applied.  Many  dyes  used  for  staining  fabrics  and  histological 
preparations  are  also  adsorbed, 


CH.  XXIV.]  REACTION   VELOCITY  329 

such  enormous  velocity  as  to  be  practically  instantaneous.  Ionic  reactions  take 
place  between  the  inorganic  constituents  of  living  cells,  but  such  reactions 
occurring  as  they  do  in  a  colloidal  medium  are  somewhat  slowed  down,  but  even 
so  are  completed  in  an  immeasurably  short  time.  The  most  important  substances 
(fats,  carbohydrates,  proteins)  in  living  tissues  are,  however,  not  electrolytes, 
and  reactions  between  them  are  spoken  of  as  molecular  reactions,  and  occur  so 
slowly  that  it  is  possible  to  ascertain  the  rate  at  which  they  take  place.  Reaction 
Velocity  is  defined  as  the  quantity  of  the  substance  transformed,  measured 
in  gramme-molecules  per  litre,  which  disappears  in  the  unit  of  time  (one  minute). 
When  starch  is  transformed  into  sugar,  or  protein  into  amino-acids,  there  is  only 
one  substance  transformed,  and  such  reactions  which  compose  the  majority  of  the 
reactions  in  living  cells  are  called  unimolecular  reactions ,  or  reactions  of  the  first 
order.  When,  for  instance,  starch  is  changed  into  sugar  by  the  action  of  an  acid, 
it  is  the  starch  alone  which  is  altered ;  the  acidity  undergoes  no  diminution. 
Similarly  when  the  change  is  brought  about  by  an  enzyme,  the  starch  only  is 
changed ;  the  enzyme  is  still  present  in  its  original  quantity.  Reaction  velocity 
is  thus  of  special  importance  in  a  study  of  the  changes  produced  by  enzymes,  and 
these  are  the  most  frequent  of  all  changes  in  living  structures. 

Since  the  quantity  of  the  substance  acted  upon  is  continually  diminishing,  the 
velocity  of  the  reaction  cannot  remain  the  same  throughout,  but  must  diminish 
in  a  certain  ratio.  Suppose  20  parts  out  of  100  are  transformed  in  the  first 
minute,  there  will  be  only  80  parts  remaining  at  the  commencement  of  the 
second  minute: — 

100  -   i|r   =  80- 
o 

Similarly  at  the  commencement  of  the  third  minute  we  have  only  64  left,  16 
having  disappeared  : — 

64. 
In  the  fourth  minute,  12-8  disappears  and  51 '2  is  left:— 

64    -    —   =   51-2; 
5 

and  so  on. 

In  order  to  express  this  in  general  terms,  we  may  label  the  original  con- 
centration 100  by  the  symbol  C0,  and  for  80,  64,  51%  etc.,  use  the  terms  Clf  C2,  C3, 
etc.  .  .  .  Ct.  The  constant  figure  in  the  above  example  is  i  or  0*2.  This  may  be 
represented  by  k.  The  equations  then  run  : — 

C«,-C0t  =  CJ,or(Ul-*)  =  C1, 

Further          C0(l  -  Jfc)  -  C0(l  -  k)  x  k  =  C2 ; 
or  C0(l-^-C2. 

Further  C0(l  -  k)3  =  C3. 

Finally  C0(l  -  ft)'  =  C;. 

If  this  is  plotted  out  in  the  form  of  a  curve,  we  obtain  the  curve  known  as  a 
logarithmic  curve. 

In  other  cases  the  law  is  a  different  one,  and  we  find  that  the  reaction  velocity 
is  not  directly  proportional  to  the  quantity  of  reacting  substance,  but  to  the  square 
of  this  quantity.  In  all  such  cases,  two  substances  are  simultaneously  changed 
in  their  concentration.  Such  a  process  takes  place  in  the  decomposition  of  esters 
(compounds  of  organic  acids  and  alcohols),  under  the  influence  of  an  alkali ;  here 
not  only  is  the  amount  of  ester  becoming  less,  but  the  alkali  is  also  used  up  in  the 
formation  of  salts  of  the  organic  acid.  Such  reactions  are  called  bimolecular 
reactions^  or  reactions  of  the  second  order.  Certain  reactions  in  living  cells  are  of 
this  order,  but  reactions  of  higher  orders  still  are  not  as  yet  known  in  living  cells. 

We  shall  again  have  to  return  to  the  study  of  molecular  reactions  when 
speaking  of  the  action  of  enzymes.  It  will  then  be  more  convenient  to  study  one 
of  the  peculiarities  they  possess,  namely,  the  phenomenon  known  as  reversibility. 


330  PHYSICAL  CHEMISTRY  [CH.  XXIV. 

Surface  Tension.— The  surface  layer  of  a  liquid  possesses  certain  properties 
which  are  not  shared  by  the  rest  of  it,  for  in  the  interior  the  arrangement  of  matter 
is  symmetrical  round  any  point,  whereas  on  the  surface  the  surroundings  consist  of 
liquid  on  one  side  only,  while  on  the  other  side  is  solid,  or  gas,  or  it  may  be  another 
liquid.  In  a  gas,  the  molecules  are  free  from  one  another's  attractive  influence 
and  fly  about  freely  with  high  velocity,  producing  pressure  on  the  walls  of  the 
containing  vessel ;  in  a  liquid,  the  mutual  attractions  of  the  molepules  are  great 
enough  to  keep  the  substance  together  in  a  definite  volume ;  in  order  to  separate 
the  molecules  and  convert  the  liquid  into  gas  a  large  amount  of  energy  is  required—- 
the so-called  latent  heat  of  evaporation.  ^The  molecular  attractions  in  a  liquid  are 
thus  very  great,  so  that  a  molecule  of  the  surface  layer  is  strongly  pulled  inwards, 
and  this  layer  constitutes  a  stretched  elastic  skin,  and  the  power  thus  exerted  is 
spoken  of  as  surface  tension.  The  effect  of  surface  tension  is  most  simply  seen  in  a 
free  drop  of  liquid,  such  as  a  rain-drop,  or  a  drop  of  oil  immersed  in  a  mixture  of 
alcohol  and  water  of  the  same  density.  There  is  then  nothing  to  prevent  the 
tension  in  the  surface  layer  from  contracting  as  much  as  possible,  and  the  drop  will 
therefore  assume  a  form  in  which  its  volume  will  have  the  smallest  surface,  that  is, 
the  drop  will  assume  the  form  of  a  sphere. 

Now  animal  cells  are  liquid,  and  when  they  are  at  rest,  other  forces  being 
absent,  they  also  are  spherical,  and  although  they  do  not  possess,  as  a  rule,  a 
definite  wall  of  cellulose  or  other  hard  substance  such  as  vegetable  cells  have, 
nevertheless  the  surface  film,  exercising  the  force  called  surface  tension,  plays  the 
part  of  an  elastic  skin,  and  is  termed  the  plasmatic  membrane.  This  membrane 
plays  an  important  physiological  role.  In  the  projection  of  pseudopodia,  for 
instance,  variations  in  the  surface  tension  must  occur  in  different  parts  of  the 
circumference  of  the  cell.  Protoplasm,  however,  is  not  a  simple  liquid,  but 
contains  substances  of  varying  chemical  composition,  and  substances  which  have 
the  power  of  diminishing  surface  tension  always  show  a  tendency  to  accumulate  at 
the  surface.  Hence  the  fats  and  lipoids  which  are  powerful  depressants  of  surface 
tension  are  found  probably  in  a  state  of  an  extremely  fine  emulsion  more 
abundantly  in  the  plasmatic  membrane  than  elsewhere  in  the  cell.  The  interstitial 
spaces  between  the  fat  globules  are  filled  up  with  a  watery  colloid  solution, 
namely  a  protein  solution.  The  theory  of  diffusion  of  dissolved  substances 
through  membranes  as  applied  to  cells  has  been  profoundly  influenced  by  the 
discovery  of  the  composition  of  the  plasmatic  membrane.  At  one  time  it  was 
believed  that  diffusion  of  a  colloid  material  was  prevented  by  the  pores  of  the 
membrane  being  too  small  to  allow  large  molecules  to  get  through  them ;  it  was 
considered  to  act  as  a  sort  of  sieve.  But  this  cannot  be  the  whole  explanation, 
and  it  is  now  held  that  solution  affinities  play  the  most  important  part ;  that  is  to 
say,  a  membrane  is  permeable  to  substances  which  are  soluble  in  the  material  of 
the  membrane.  Such  solubility  may  imply  the  formation  of  actual  chemical 
unions,  or  more  frequently  the  process  is  one  of  adsorption ;  this  latter  process 
comes  specially  into  play  when  nutritive  materials  are  assimilated  by  the  cell  by 
means  of  the  protein  solution  which  occupies  the  interstices  between  the  fat 
globules.  On  the  other  hand,  the  permeability  of  the  plasmatic  membrane  by 
substances  such  as  alcohol,  chloroform,  and  ether,  is  mainly  determined  by  the 
solubility  of  these  materials  in  the  fatty  or  fat-like  components  of  the  membrane, 
and  this  consideration  is  the  foundation  of  the  Meyer-Over  ton  theory  of  the  narcotic 
effect  on  cells  which  these  volatile  anaesthetics  exercise. 


CHAPTER  XXV 

THE   DUCTLESS    GLANDS 

THE  ductless  glands  form  a  heterogeneous  group  of  organs,  most  of 
which  are  related  in  function  or  development  with  the  circulatory 
system.  The  function  of  a  gland  that  has  a  duct  is  a  comparatively 
simple  physiological  problem,  but  the  use  of  ductless  glands  was 
for  long  a  puzzle  to  investigators.  Kecent  research  has,  however, 
shown  that  most  of,  if  not  all,  the  ductless  glands  do  form  a 
secretion,  and  this  internal  secretion,  as  it  is  termed,  leaves  the 
gland  by  the  venous  blood  or  lymph,  and  thus  is  distributed  and 
ministers  to  the  needs  of  parts  of  the  body  elsewhere.  Many  of 
the  glands  which  possess  ducts  and  form  an  external  secretion,  form 
an  internal  secretion  as  well.  Among  these,  the  liver  and  pancreas 
may  be  mentioned.  The  term  internal  secretion  was  first  used  by 
Claude  Bernard  in  relation  to  the  liver. 

In  many  cases  the  internal  secretion  is  essential  for  life,  and 
removal  of  the  gland  that  forms  it,  leads  to  a  condition  of  disease 
culminating  in  death.  In  other  cases  the  internal  secretion  is  not 
essential,  or  its  place  is  taken  by  that  formed  in  similar  glands  in 
other  parts  of  the  body. 

The  body  is  a  complex  machine ;  each  part  of  the  machine  has 
its  own  work  to  do,  but  must  work  harmoniously  with  other  parts. 
Just  as  a  watch  will  stop  if  any  of  its  numerous  wheels  get  broken, 
so  the  metabolic  cycle  will  become  disarranged  or  cease  altogether  if 
any  of  the  links  in  the  chain  break  down. 

In  unravelling  the  part  which  the  ductless  glands  play  in  this 
cycle,  it  is  at  present  impossible  in  many  cases  to  state  precisely 
what  the  particular  function  of  each  is;  all  one  can  say  is,  when 
the  gland  is  removed  or  its  function  interfered  with,  that  the  meta- 
bolic round  is  broken  somehow,  and  that  this  upsets  the  rest  of 
the  machinery  of  the  body.  The  difficulty  of  investigating  this 
subject  is  increased  by  the  fact  that  it  is  impossible  to  get  the 
internal  secretion  in  a  state  of  purity  and  examine  it ;  it  is  always 

831 


332  THE   DUCTLESS   GLANDS  [CH.  XXV. 

mixed  with,  and  masked  by,  the  lymph  or  blood  into  which  it  is 
poured. 

In  spite  of  this,  however,  our  knowledge  in  this  branch  of 
physiology  is  increasing,  particularly  in  connection  with  some  of 
these  ductless  glands.  The  methods  of  investigation  which  have 
been  employed  are  the  following : — 

1.  Extirpation. — The   gland    in    question    is   removed,   and   the 
effect  of  the  absence  of  the  internal  secretion  noted. 

2.  Disease. — In  cases   where   the  function   of   the  gland   is  in 
abeyance,  owing   to   its   being  diseased,  the  symptoms  are   closely 
observed. 

3.  Injection  of  Extracts. — The  gland  is  taken  in  a  fresh  condition ; 
an  extract  is  made   of  it,  and  this  is  injected  into  the  circulation 
of  healthy  animals,  and  into  that  of  those  animals  from  which  the 
gland  has  been  previously  removed,  and  the  effects  watched. 

4.  Transplantation. — After  the  gland  is  removed  and  the  usual 
effect  produced,  the  same  gland  from  another  animal  is  transplanted 
into  the  first  animal,  and  restoration  of  function  looked  for. 

The  case  of  the  lymphatic  glands  we  have  already  studied ;  they 
furnish  the  blood  with  a  supply  of  a  certain  kind  of  colourless 
corpuscle.  Eemoval  of  lymphatic  glands  is  not  fatal,  as  the  other 
lymphatic  glands  and  other  collections  of  lymphoid  tissue  that  remain 
behind  carry  on  the  work  of  those  that  are  removed. 

The  internal  secretion  theory  of  the  ductless  glands  is  that  which  is  most  in 
vogue  at  present.  It  should  be  mentioned,  however,  that  there  is  another  theory, 
which  may  be  called  the  auto-intoxication  theory.  According  to  this  view  the  gland 
is  excretory  (i.e.,  gets  rid  of  waste  and  harmful  materials)  rather  than  secretory  (i.e., 
production  of  something  useful  to  the  organism).  When  the  gland  is  removed, 
the  waste  products  therefore  accumulate  and  produce  harmful  results.  It  is 
possible  that  as  our  knowledge  increases,  it  may  be  found  in  certain  cases  that 
both  these  theories  may  be  in  part  true. 

The  Spleen. 

The  Spleen  is  the  largest  of  the  ductless  glands ;  it  is  situated 
to  the  left  of  the  stomach.  It  is  of  a  deep  red  colour  and  of 
variable  shape.  Vessels  enter  and  leave  the  gland  at  a  depres- 
sion on  the  inner  side  called  the  hilus.  The  spleen  is  covered 
externally  almost  completely  by  a  serous  coat  derived  from  the 
peritoneum,  while  within  this  is  the  proper  fibrous  coat  or  capsule 
of  the  organ.  The  latter  contains  numerous  elastic  fibres  and  a 
large  amount  of  unstriated  muscular  tissue.  Prolonged  from  its 
inner  surface  are  fibrous  processes  or  trabeculce,  containing  much 
unstriated  muscle,  which  enter  the  interior  of  the  organ,  and, 
dividing  and  anastomosing  in  all  parts,  form  a  supporting  frame- 
work in  the  interstices  of  which  the  proper  substance  of  the  spleen 
(spleen-pulp)  is  contained. 


en.  xxv.] 


THE   SPLEEN 


333 


The  spleen-pulp,  which  is  of  a  dark  red  or  reddish-brown  colour, 
is  composed  chiefly  of  cells,  imbedded  in  a  network  formed  of  fibres, 
and  the  branchings  of  large  nucleated  cells.  The  network  so  formed  is 
thus  very  like  a  coarse  kind  of  retiform  tissue.  Some  of  the  cells  in  the 
meshes  of  the  network  are  granular  corpuscles  resembling  the  lymph- 


FIG.  277.— Section  of  injected  dog's  spleen,  c,  Capsule  ;  tr,  trabeculse ;  m,  two  Malpighian  bodies  with 
numerous  small  arteries  and  capillaries ;  a,  artery ;  I,  lymphoid  tissue,  consisting  of  closely  packed 
lymphoid  cells  supported  by  very  delicate  retiform  tissue  ;  a  light  space  unoccupied  by  cells  is  seen 
all  round  the  trabeculae,  which  corresponds  to  the  "lymph-path  "  in  lymphatic  glands.  (Schofleld.) 

corpuscles,  both  in  general  appearance  and  in  being  able  to  perform 
amoeboid  movements;  others  are  red  blood-corpuscles  of  normal 
appearance  or  variously  changed;  while  there  are  also  large  cells 
containing  either  a  pigment  allied  to  the  colouring  matter  of  the 
blood,  or  rounded  corpuscles  like  red  corpuscles. 

The  splenic  artery,  after  entering  the  spleen  divides  into  branches, 
which  soon  leave  the  trabeculae,  with  which  at  first  they  are 
sheathed,  and  their  outer  coat  is  then  replaced  by  one  of  lymphoid 
tissue;  they  end  in  an  open  brushwork  of  capillaries,  the  endo- 
thelial  cells  of  which  become  continuous  with  those  of  the  rete  of 
the  spleen-pulp.  The  veins  begin  by  a  similar  open  set  of  capil- 


334  THE   DUCTLESS    GLANDS  [CH.  XXV. 

laries  from  the  large  blood  spaces  of  the  pulp.  The  veins  soon 
pass  into  the  trabeculce,  and  ultimately  unite  to  form  the  splenic 
vein.  This  arrangement  readily  allows  lymphoid  and  other  corpuscles 
to  be  swept  into  the  blood -current. 

On  the  face  of  a  section  of  the  spleen  can  be  seen  usually  readily 
with  tin  naked  eye,  minute,  scattered,  rounded  or  oval  whitish 
spots,  mostly  from  -JF  to  -^  inch  (f  to  f  mm.)  in  diameter.  These 
are  the  Malpighian  corpuscles  of  the  spleen,  and  are  situated  on  the 
sheaths  of  the  minute  splenic  arteries.  They  are  in  fact  outgrowths 
of  the  outer  coat  of  lymphoid  tissue  just  referred  to  (see  fig.  277). 
Blood  capillaries  traverse  the  Malpighian  corpuscles  and  form  a 
plexus  in  their  interior.  The  structure  of  a  Malpighian  corpuscle  of 
the  spleen  is  practically  identical  with  that  of  a  lymphoid  nodule. 

The  spleen  has  the  following  functions : — 

(1.)  The  spleen,  like  the  lymphatic  glands,  is  engaged  in  the 
formation  of  colourless  Hood-corpuscles.  For  it  is  quite  certain, 
that  the  blood  of  the  splenic  vein  contains  an  unusually  large 
proportion  of  white  corpuscles;  and  in  the  disease  termed  leuco- 
cythcemia,  in  which  the  white  corpuscles  of  the  blood  are  remarkably 
increased  in  number,  there  is  found  a  hypertrophied  condition  of 
the  spleen,  especially  of  the  Malpighian  corpuscles.  The  white 
corpuscles  formed  in  the  spleen  also  doubtless  partly  leave  that 
organ  by  lymphatic  vessels. 

By  stimulating  the  spleen  to  contract  in  a  case  of  splenic 
leucocythaemia  by  means  of  an  electric  current  applied  over  it  through 
the  skin,  the  number  of  leucocytes  in  the  blood  is  almost  immediately 
increased. 

Eemoval  of  the  spleen  is  not  fatal;  but  after  its  removal 
there  is  an  overgrowth  of  the  lymphatic  glands  to  make  up  for 
its  absence. 

(2.)  It  forms  coloured  corpuscles,  at  any  rate,  in  some  animals ;  in 
these  animals,  cells  are  found  in  the  spleen  similar  to  those  we  have 
described  in  red  marrow,  and  called  Jiccmatoblasts.  In  these  animals, 
if  the  spleen  is  removed,  the  red  marrow  hypertrophies. 

(3.)  There  is  reason  to  believe  that  in  the  spleen  many  of  the  red 
corpuscles  of  the  blood,  those  probably  which  have  discharged  their 
office  and  are  worn  out,  undergo  disintegration ;  for  in  the  coloured 
portions  of  the  spleen-pulp  an  abundance  of  such  corpuscles,  in  various 
stages  of  degeneration,  are  found,  and  in  those  cases  of  disease  in 
which  the  destruction  of  blood-corpuscles  is  increased  (pernicious 
anaemia),  iron  accumulates  in  the  spleen  as  in  the  liver.  It  was 
formerly  supposed  that  the  spleen  broke  down  the  corpuscles  and 
liberated  hsemoglobin,  which,  passing  in  the  blood  of  the  splenic  vein 
to  the  liver,  was  discharged  by  that  organ  as  bile-pigment.  But  this 
is  not  the  case;  the  disintegration  does  not  proceed  so  far  as  to 


CH.  XXV.]  THE   SPLEEN  335 

actually  liberate  haemoglobin;  there  is  no  free  haemoglobin  in  thfe 
blood-plasma  of  the  splenic  vein. 

(4.)  The  spleen  participates  in  nitrogenous  metabolism,  especially 
in  the  formation  of  uric  acid  (see  Uric  Acid  formation  in  Chapter 
on  Urine). 

(5.)  Besides  these  direct  offices,  the  spleen  fulfils  some  purpose 
in  regard  to  the  portal  circulation  with  which  it  is  in  close  connec- 
tion. From  the  readiness  with  which  it  admits  of  being  distended, 
and  from  the  fact  that  it  is  generally  small  while  gastric  digestion  is 
going  on,  and  enlarges  when  that  act  is  concluded,  it  is  supposed  to 
act  as  a  kind  of  vascular  reservoir,  or  diverticulum  to  the  portal 


0.  PRESSURE 


FJCJ.  278. — The  upper  tracing  is  the  spleen  record;  the  next  is  carotid  blood -pressure  taken  with  a 
mercurial  kymograph.  The  straight  line  beneath  this  is  the  abscissa  of  the  arterial  pressure  ;  and 
the  lowest  tracing  is  the  time  in  seconds. 

system,  or  more  particularly  to  the  vessels  of  the  stomach.  This 
mechanical  influence  on  the  circulation,  however,  can  hardly  be 
supposed  to  be  more  than  a  very  subordinate  function.  The  main 
use  of  the  contractility  of  the  spleen  is  to  assist  the  passage  of  the 
blood  through  itself. 

It  has  been  found  by  experiment  that  when  the  splenic  nerves 
are  cut  the  spleen  enlarges,  and  that  contraction  can  be  brought 
about  by  stimulation  of  the  peripheral  ends  of  the  divided  nerves. 
If  the  splenic  nerves  are  not  cut,  contraction  is  produced  by 
(1)  stimulation  of  the  spinal  cord ;  (2)  reflexly  by  stimulation  of 
the  central  stumps  of  certain  divided  nerves,  e.g.,  vagus  and  sciatic ; 
(3)  by  local  stimulation  by  an  electric  current;  (4)  by  the  admini- 
stration of  quinine  and  some  other  drugs. 


336  THE  DUCTLESS   GLANDS  [CH.  XXV. 

It  has  been  shown  by  the  oncometer  (see  p.  309)  that  the  spleen 
undergoes  rhythmical  contractions  and  dilatations,  due  to  the  con- 
traction and  relaxation  of  the  muscular  tissue  in  its  capsule  and 
trabeculae.  A  tracing  also  shows  waves  due  to  the  rhythmical  alter- 
ations of  the  general  blood-pressure.  Fig.  278  is  a  typical  tracing 
obtained  by  Schafer's  air  oncometer  from  a  dog's  spleen. 

It  shows,  first,  the  large  waves  occurring  about  once  a  minute, 
due  to  the  splenic  systole  and  diastole;  secondly,  smaller  waves  on 
this,  due  to  the  effect  of  respiration  on  the  blood-pressure ;  and  on 
these,  smaller  waves  still,  corresponding  with  the  individual  heart- 
beats. The  large  waves  due  to  the  splenic  contractility  still  go  on 
after  the  division  of  all  the  splenic  nerves.  These  nerve-fibres  leave 
the  spinal  cord  in  numerous  thoracic  anterior  roots ;  they  have  cell- 
stations  in  the  sympathetic  chain  (Schafer)  or  semi-lunar  ganglia 
(Langley). 

Haemolymph  Glands. 

The  existence  of  glands  which  partake  of  the  nature  both  of  the 
spleen  and  of  lymphatic  glands,  has  long  been  known.  They  have 
been  recently  more  fully  investigated  by  T.  Lewis.  He  finds  them  in 
most  mammals,  and  they  can  be  readily  distinguished  from  ordinary 
lymphatic  glands  by  their  red  colour.  He  divides  them  into  (1)  hcemal 
glands,  which  are  characterised  by  the  fact  that  the  sinuses  contain 
blood  only;  the  spleen  is  in  fact  a  large  haemal  gland;  and  (2) 
hcemal  lymphatic  glands,  in  which  the  sinuses  are  filled  by  a  mixture 
of  blood  and  lymph. 

The  Thymus. 

This  gland  attains  its  greatest  size  soon  after  birth,  and  after  the 
second  year  it  gradually  diminishes,  until  in  adult  life  hardly  a 
vestige  remains;  it  is  then  replaced  by  adipose  and  connective 
tissue.  This,  at  any  rate,  has  been  the  general  belief  until  the  last 
few  years.  Some  recent  observations,  however,  appear  to  show  that 
the  thymus  persists  longer,  and  may  grow  until  puberty ;  and  that 
some  true  thymus  tissue  may  persist  throughout  life. 

The  gland  is  surrounded  by  a  fibrous  capsule,  which  sends  in 
processes,  forming  trabeculas,  that  divide  the  gland  into  lobes,  and 
carry  the  blood-  and  lymph-vessels.  The  large  trabeculse  branch  into 
small  ones,  which  divide  the  lobes  into  lobules.  The  lobules  are 
further  subdivided  into  follicles  by  fine  connective  tissue.  A  follicle 
is  polyhedral  in  shape,  and  consists  of  cortical  and  medullary  por- 
tions, both  of  which  are  composed  of  adenoid  or  lymphoid  tissue, 
but  in  the  medullary  portion  the  matrix  is  coarser,  and  is  not  so 
filled  up  with  lymphoid  corpuscles  as  in  the  cortex.  Scattered  in 
the  lymphoid  tissue  of  the  medulla  are  the  concentric  corpuscles  of 


CH.  XXV.]  THE   THYROID  337 

Hassall  (fig.  279),  which  are  nests  or  islands  of  epithelial  cells  cut  off 
from  the  epithelium  of  the  pharynx  in  process  of  development. 

The  functions  of  the  thymus  are  very 
obscure.  It  has  generally  been  assumed  that 
the  lymphoid  tissue  of  which  it  is  composed 
form  colourless  corpuscles ;  but  Stohr  asserts 
that  it  is  not  true  lymphoid  tissue. 

It  has  been  stated  that  in  hibernating 
animals,  in  which  it  undoubtedly  persists 
throughout  life,  that  as  each  hibernating 
period  approaches  the  gland  enlarges,  and  its 
cells  become  laden  with  fat.  In  this  case,  the 
store  of  fat  will  serve  to  maintain  combustion 
processes  during  the  winter  sleep.  ceiis ;  6  corpus 

TH  i      D    ^          ^        j     '       ii       £  •        A.    A.    j  Hassall.    (Cadiat.) 

Eemoval  of  the  gland  in  the  frog  is  stated 

to  be  followed  by  muscular  weakness,  paralysis,  and  finally  death ; 
but  later  observations  have  failed  to  confirm  this  result,  either  in 
frogs  or  mammals.  Intravenous  injection  of  extracts  of  thymus 
lowers  arterial  blood-pressure  and  accelerates  the  heart,  but  extracts  of 
most  organs  produce  similar  effects,  especially  on  the  blood-pressure. 

Lately  it  has  been  suggested  that  there  is  some  relationship  between 
the  thymus  and  the  generative  organs ;  and  this  view  is  supported  by 
the  circumstance  that  castration  retards  the  atrophy  of  the  thymus, 
whilst  removal  of  the  thymus  hastens  the  growth  of  the  testes. 

The  Thyroid. 

The  thyroid  gland  is  situated  in  the  neck.  It  consists  of  two 
lobes,  one  on  each  side  of  the  trachea;  these  lobes  are  connected 
across  the  middle  line  by  a  middle  lobe  or  isthmus.  It  is  highly 
vascular,  and  varies  in  size  in  different  individuals. 

The  gland  is  encased  in  a  capsule  of  dense  areolar  tissue.  This 
sends  in  strong  fibrous  trabeculae,  which  enclose  the  thyroid  vesicles — 
which  are  rounded  or  oblong  sacs,  consisting  of  a  wall  of  thin 
hyaline  membrane  lined  by  a  single  layer  of  short  cylindrical  or 
cubical  cells.  These  vesicles  are  filled  with  transparent  colloid 
nucleo-protein  material.  The  colloid  substance  increases  with  age, 
and  the  cavities  appear  to  coalesce.  In  the  interstitial  connective- 
tissue  is  a  round  meshed  capillary  plexus,  and  a  large  number  of 
lymphatics.  The  nerves  adhere  closely  to  the  vessels. 

In  the  vesicles  there  are  sometimes,  in  addition  to  the  yellowish 
glassy  colloid  material,  epithelium  cells,  colourless  blood-corpuscles, 
and  also  coloured  corpuscles  undergoing  disintegration. 

It  is  difficult  to  state  definitely  the  function  of  the  thyroid  body  ; 
it  is  one  of  those  organs  of  great  importance  in  the  metabolic  round ; 
and  its  removal  or  disease  is  followed  by  general  disturbances.  It  no 

Y 


338 


THE   DUCTLESS   GLANDS 


fCH.  XXV. 


doubt  forms  an  internal  secretion ;  to  this  the  colloid  material  men- 
tioned contributes,  as  it  is  found  in  the  lymphatic  vessels  of  the  organ. 

When  the  gland  is  diseased  in  children  and  its  function  obliterated, 
a  species  of  idiocy  is  produced  called  cretinism, 

The  same  condition  in  adults  is  called  myxcedema ;  the  most 
marked  symptoms  of  this  condition  are  slowness,  both  of  body  and 
mind,  usually  associated  with  tremors  and  twitchings.  There  is  also 
a  peculiar  condition  of  the  skin  leading  to  the  overgrowth  of  the 
subcutaneous  tissues,  which  in  time  is  replaced  by  fat ;  the  hair  falls 
off,  the  hands  become  spade-like;  the  whole  body  is  unwieldy  and 
clumsy  like  the  mind. 

A  similar  condition  occurs  after  the  thyroid  is  completely  removed 


FIG.  280.— Section  of  human  thyroid;  the  few  vesicles  shown  are  lined  by  cubical  epithelium,  and  con- 
tain a  colloid  material.    (After  Bchiifer.) 

surgically ;  this  is  called  cackexia  strumipriva ;  this  operation,  which 
was  performed  previous  to  our  knowledge  of  the  importance  of  the 
thyroid,  is  of  course  not  performed  nowadays. 

Lastly,  in  many  animals  removal  of  the  thyroid  produces  analogous 
symptoms,  in  the  overgrowth  of  the  connective  tissues  especially 
under  the  skin,  a'nd  in  the  nervous  symptoms  (twitchings,  convul- 
sions, etc.). 

The  term  Myxcedema  was  originally  given  under  the  erroneous 
idea  that  the  swelling  of  the  body  is  due  to  mucin.  In  the  early 
stages  of  the  disease  there  is  a  slight  increase  of  mucin,  because 
all  new  connective  tissues  contain  a  relatively  large  amount  of  ground 
substance,  the  most  abundant  constituent  of  which,  next  to  water, 
is  mucin.  But  there  is  nothing  characteristic  about  that. 


CU.  XXV.]  THE    PARATHYROIDS  339 

The  discovery  of  the  relationships  between  the  thyroid  and  these 
morbid  conditions  is  especially  interesting,  because  important  practical 
results  in  their  treatment  have  followed  close  on  the  heels  of  experi- 
mental investigation.  The  missing  internal  secretion  of  the  thyroid 
may  be  replaced  in  these  animals  and  patients  by  grafting  the  thyroid 
of  another  animal  into  the  abdomen;  or  more  simply  by  injecting 
thyroid  extract  subcutaneously ;  or  even  by  feeding  on  the  thyroid 
of  other  animals.  This  treatment,  which  has  to  be  kept  up  for  the 
rest  of  the  patient's  life,  is  entirely  successful.  Chemical  physiologists 
have  been  diligently  searching  to  try  and  discover  what  the  active 
material  in  thyroid  extract  is  which  produces  such  marvellous 
results;  the  view  at  present  held  is  that  the  efficacy  of  thyroid 
extract  is  mainly  though  not  entirely  due  to  a  substance  which 
Baumann  separated  from  the  gland,  and  which  stands  almost  unique 
among  physiological  compounds  by  containing  a  large  percentage 
of  iodine  in  its  molecule.  Thyro-iodin  or  lodo-thyrin,  as  this 
substance  has  been  called,  is  present  in  combination  with  protein 
matter  in  the  colloid  substance. 

Intravenous  injection  of  thyroid  extract  in  a  normal  animal 
lowers  blood-pressure ;  but  in  an  animal  from  which  the  thyroid  has 
been  removed  it  stimulates  the  heart  and  raises  blood-pressure. 

In  healthy  animals  and  men,  administration  of  thyroid  produces 
an  increase  in  nitrogenous  metabolism. 

Parathyroids. 

These  are  small  bodies,  usually  four  in  number,  situated  near 
or  imbedded  in  the  substance  of  the  thyroid.  They  are  made  up 
of  elongated  groups  of  polyhedral  cells,  bound  together  by  connec- 
tive tissue,  and  well  supplied  with  blood-vessels.  Some  have 
supposed  that  parathyroid  is  only  immature  thyroid  tissue,  but  a 
study  of  development  shows  that  the  parathyroids  have  a  different 
embryonic  origin  from  the  thyroid,  and  in  the  lower  vertebrates  the 
two  organs  are  entirely  distinct.  It  is  only  in  the  mammals  that 
they  are  so  closely  associated  anatomically.  They  are  probably 
associated  physiologically  also,  and  it  has  been  by  no  means  easy 
to  determine  the  role  of  each.  Most  of  the  facts  described  in  the 
preceding  section  on  the  thyroid  were  discovered  previous  to  the 
recognition  of  the  parathyroids,  and  since  then  the  view  has  been 
advanced  that  in  removing  the  thyroid  it  is  really  the  simultaneous 
removal  of  the  parathyroids  which  causes  the  nervous  symptoms. 
Certainly  the  most  prominent  symptom  after  extirpation  of  the 
parathyroids  is  tetany  (muscular  spasms  and  twitchings). 

The  parathyroids  contain  no  iodine,  and  it  is  doubtful  if 
they  form  an  internal  secretion.  If  they  do  not,  their  function 
must  be  to  neutralise  poisonous  substances  formed  elsewhere,  and 


340 


THE   DUCTLESS    GLANDS 


[CH.  XXV. 


the  symptoms  after  extirpation  will  then  be  due  to  the  toxic  effect 
of  an  accumulation  of  the  poison.  It  has  further  been  shown  that 
tetany  produced  in  animals  and  men  by  parathyroidectomy  can  be 
relieved  by  the  administration  of  calcium  salts,  and  so  it  is  possible 
that  the  parathyroids  may  be  related  in  some  way  to  calcium 
metabolism. 

The  Suprarenal  Capsules. 

These  are  two  triangular  or  cocked-hat-shaped  bodies,  each  resting 
by  its  lower  border  upon  the  upper  border  of  the  kidney. 

The  gland  is  surrounded  by  an  outer  sheath  of  connective  tissue, 
which  sends  in  fine  prolongations  forming  the  framework  of  the  gland. 
The  gland  tissue  proper  consists  of  an  outside  firmer  cortical  portion 
and  an  inside  soft,  dark  medullary  portion. 

(1)  The  cortical  portion  is  divided  into  (fig.  281)  columnar  groups 


FIG.  281.— Vertical  section  through  part  of  the  cortical  portion  of  suprarenal  of  guinea-pig,  a,  Cap- 
sule ;  b,  zona  glomerulosa ;  c,  zona  fasciculata  ;  d,  connective  tissue  supporting  the  columns  of  the 
cells  of  the  latter,  and  also  indicating  the  position  of  the  blood-vessels.  (S.  K.  Alcock.) 

of  cells  (zona  fasciculata).  Immediately  under  the  capsule,  however, 
the  groups  are  more  rounded  (zona  glomerulosa),  while  next  to  the 
medulla  they  have  a  reticular  arrangement  (zona  reticularis).  The 
cells  themselves  are  polyhedral,  each  with  a  clear  round  nucleus,  and 
contain  lipoid  globules. 

(2)   The   medullary  substance  consists   of   a   coarse   rounded    or 
irregular  meshwork  of  fibrous  tissue,  in  the   alveoli  of   which  are 


CH.  XXV.] 


THE  SUPRARENAL  CAPSULES 


341 


masses  of  multinucleated  protoplasm  (fig.  282),  numerous  blood-vessels 
(sinusoids,  see  p.  222),  and  an  abundance  of  nerve-fibres  and  cells. 

The  cells  of  the  medulla  are  characterised  by  the  presence  of 
certain  reducing  substances.  One  of  these  takes  a  brown  stain  with 
chromic  acid,  and  gives  other  colour  reactions ;  it  is,  therefore,  called 
a  chromogen.  Another  is  similar  in  many  of  its  characters  to  jecorin, 
a  lecithin-like  substance  united  to  glucose  also  found  in  the  liver, 
spleen,  and  other  organs. 

The  immense  importance  of  the  suprarenal  bodies  was  first  in- 
dicated by  Addison,  who,  in  1855,  pointed  out  that  the  disease  now 
known  by  his  name  is  associated  with  pathological  alterations  of  these 


iteipwii«^:v, 

lilffp^ 

'  v  ~v  :'V'      Ws^iMww&m  -•/••V'^y^--V?---'-'':.;r.\      /.'•'* 
^-    /  •     .'>  *•$.•.••."••.•.">•:  •"•.  .V-v.-..-..-,  Vv^iui; 


•/:  '  ; 


FIG.  282.—  Section  through  a  portion  of  the  medullary  part  of  the  suprarenal  of  guinea-pig.  The 
vessels  are  very  numerous,  and  the  fibrous  stroma  more  distinct  than  in  the  cortex,  and  is,  more- 
over, reticulated.  The  cells  are  irregular  and  larger,  clear,  and  free  from  oil  globules.  (S.  K. 
Alcock.) 

glands.  This  was  tested  experimentally  by  Brown-Sequard,  who 
found  a  few  years  later  that  removal  of  the  suprarenals  in  animals  is 
invariably  and  rapidly  fatal.  The  symptoms  are  practically  the 
same  (although  more  acute)  as  those  of  Addison's  disease,  namely, 
great  muscular  weakness,  loss  of  vascular  tone,  and  nervous  prostra- 
tion. The  pigmentation  (bronzing)  of  the  skin,  however,  which  is  a 
marked  symptom  in  Addison's  disease,  is  not  seen  in  animals.  The 
experiments  of  Brown-Sequard  attracted  much  attention  at  the  time 
they  were  performed,  but  were  almost  forgotten  for  many  years, 
until  they  were  confirmed  by  Abelous,  Langlois,  Schafer,  and  others. 
The  effects  on  the  muscular  system  are  the  most  marked  results  both 
after  removal  of  the  capsules  and  after  injection  of  an  extract  of  the 
glands.  The  effect  of  injecting  such  an  extract  on  the  voluntary 
muscles  is  to  increase  their  tone,  so  that  a  tracing  obtained  from  them 
resembles  that  produced  by  a  small  dose  of  veratrine,  namely,  a  pro- 


342  THE    DUCTLESS    GLANDS  [CH.  XXV. 

longation  of  the  period  of  relaxation.  The  effect  on  involuntary 
muscle  is  even  more  marked ;  there  is  an  enormous  rise  of  arterial  blood- 
pressure  due  chiefly  to  a  contraction  of  the  arterioles.  This  is  produced 
by  the  direct  action  of  the  extract  on  the  arterioles,  not  an  indirect 
one  through  the  vaso-motor  centre.*  The  substance  in  the  extract  that 
produces  the  effect  is  known  as  adrenaline;  it  is  confined  to  the 
medulla  of  the  capsules,  and  is  absent  in  cases  of  Addison's  disease. 

The  suprarenal  bodies,  therefore,  form  something  which  is  dis- 
tributed to  the  muscles  and  is  essential  for  their  normal  tone ;  when 
they  are  removed  or  diseased,  the  effects  seen  are  the  result  of  the 
absence  of  this  internal  secretion. 

Adrenaline  has  received  various  names  from  the  different  chemists 
(Abel,  v.  Fiirth,  Takamine,  etc.),  who  have  isolated  it.  It  is  very 
powerful ;  solutions  of  one  part  in  a  million  will  produce  physio- 
logical effects.  Its  composition  is  shown  by  the  following  formula : — 

OH 

/\  OH 


CH.OH.CH,.NH.CH.j 

and  it  is  therefore  a  methyl-amino  derivative  of  catechol  (Pauly, 
Jowett).  Eecently,  compounds  closely  allied  to  it  in  composition 
and  action  have  been  made  synthetically  (Stolz,  Friedmann,  Dakin). 

Whether  this  discovery  will  lead  to  the  same  kind  of  results,  as 
in  the  case  of  the  thyroid,  must  be  left  to  the  future  to  decide. 
There  is  already  some  evidence  to  show  that  injection  of  suprarenal 
extract  is  beneficial  in  cases  of  Addison's  disease.  The  discovery  of 
adrenaline  itself  is,  however,  one  of  immense  practical  importance. 
Its  action  on  the  small  blood-vessels  is  so  powerful  that  quite  weak 
solutions  applied  locally  will  subdue  the  congestion  of  inflammation 
and  even  arrest  haemorrhage. 

The  splanchnic  nerves  have  been  shown  to  contain  secretory  fibres 
which  control  the  amount  of  adrenaline  poured  into  the  circulation. 

The  use  of  the  suprarenal  cortex  is  still  unknown.  It  has  been 
suggested  that  it  has  some  effect  on  the  development  of  the  organs  of 
generation,  but  these  views  are  quite  hypothetical.  The  cortex,  how- 
ever, contains  large  quantities  of  lipoid  material  (cholesterin,  lecithin, 
and  similar  substances),  and  the  droplets  seen  in  the  fresh  cells  consist 
of  these  compounds ;  the  suggestion  that  the  suprarenal  cortex  plays 
a  part  in  the  metabolism  of  these  substances  appears  to  be  the  only 
feasible  one  at  present. 

*  It  is  the  sympathetic  nerve  terminals  which  are  really  affected.  Any  muscular 
tissue  supplied  by  sympathetic  nerves  contracts  under  the  influence  of  adrenaline. 
Vessels  destitute  of  constrictor  fibres  (coronary,  pulmonary  and  cerebral)  are  not 
contracted  by  adrenaline. 


CH.  XXV.]  THE   PITUITARY  BODY  343 

There  are  some  points  of  interest  in  the  development  and  com- 
parative physiology  of  the  suprarenals.  In  mammals  the  medullary 
portion  is  developed  in  connection  with  the  sympathetic,  and  is  at 
first  distinct  and  outside  the  cortical  portion  which  is  developed  in 
connection  with  the  upper  part  of  the  Wolffian  body ;  it  gradually 
insinuates  itself  within  the  cortex  (Mitsukiri).  In  Elasmobranch 
fishes  the  suprarenals  consist  throughout  life  of  separate  portions ; 
one,  the  inter-renal  body,  is  median  in  position  and  single ;  this  corre- 
sponds to  the  cortex  of  the  mammalian  suprarenal ;  extracts  of  this 
are  inactive,  and  in  the  Teleostean  fishes,  where  it  is  the  sole  repre- 
sentative of  the  suprarenal,  it  may  be  removed  without  any  harm  to 
the  animal.  The  other  portion  of  the  Elasmobranch  suprarenal  is 
paired,  and  derived  from  the  sympathetic  ganglia.  This  corresponds 
to  the  medulla ;  it  contains  the  same  chromogen  as  the  medulla  of 
the  mammalian  suprarenal,  and  extracts  of  it  have  the  same  physio- 
logical action  (S.  Vincent). 

The  tissue  of  the  suprarenal  medulla  is  often  called  chrcmophil  tissue,  on 
account  of  the  ready  way  in  which  it  stains  with  chromic  salts.  Such  tissue  is, 
moreover,  not  confined  to  the  suprarenal,  but  is  found  in  scattered  patches  in  the 
retro-peritoneal  region  and  in  many  sympathetic  ganglia,  especially  in  the 
abdomen.  The  histological  resemblance  is  accentuated  by  the  presence  of 
numerous  sympathetic  cells  in  the  suprarenal  medulla.  The  chromophil  tissue 
wherever  found  always  yields  adrenaline. 

The  Pituitary  Body. 

This  occupies  the  sella  turcica  of  the  sphenoid  bone.  It  may  be 
divided  into  three  parts,  which  show  developmental,  structural  and 
functional  differences. 

(1)  The  anterior  lobe  is  developed  as  a  tubular  prolongation  from 
the  epiblast  of  the  buccal  cavity,  but   the  growth  of   intervening 
tissue  soon  cuts  off  all  connection  with  the  mouth.     It  consists  of 
large  granular  cells  and  numerous  blood-vessels.     Its  precise  function 
is  undetermined,  although  probably  it  is  a  vascular  gland  pouring 
an    internal    secretion    into    the   blood,   which   influences    growth. 
Abnormal   hypertrophy   of    the   pituitary    produces    the    condition 
known  as  acromegaly,  in  which  the  bones  of   the  face  and   limbs 
hypertrophy ;  and  if  the  view  advanced  above  of  the  anterior  lobe 
is   correct,  the  condition  is   caused  by  an  increase  of  the  internal 
secretion.      Feeding   young   animals   and  children   in   the   anterior 
lobe  hastens  the  growth  of  their  skeletal  tissues.  »  5.-,;°     |-H.~  " 

(2)  The  pars  intermedia. — This  lies  between  the  anterior   and 
posterior  lobes,  and  forms  a  closely  fitting  investment  of  the  latter 
lobe.     It  is  developed  in   association  with  the  anterior  lobe,  and 
consists  of  finely  granular  cells  arranged  in  layers  closely  applied  to 
the  body  and  neck  of  the  posterior  lobe  and  the  under  surface  of 
adjacent  parts  of   the  brain.     Colloid  material  occurs  between  the 


344  THE  DUCTLESS   GLANDS  [CH.  XXV. 

cells,  which  passes  into  the  adjacent  nervous  substance,  to  be  absorbed 
by  lymphatics  which  carry  it  to  the  cavity  of  the  posterior  lobe,  and 
so  into  the  third  ventricle  of  the  brain.  The  existence  of  colloid 
cysts  in  the  pituitary  closely  resembling  those  of  the  thyroid  has 
led  many  observers  to  the  conclusion  that  the  function  of  the  two 
glands  is  similar,  and  that  after  removal  of  the  thyroid  the  pituitary 
may  take  on  its  work  vicariously.  After  extirpation  of  the  thyroid 
gland,  the  cells  of  the  pars  intermedia  do  manifest  increased  activity, 
and  the  colloid  matter  increases  but  this  is  all  that  can  be  said  at 
present  in  favour  of  such  a  view;  the  removal  of  the  two  organs 
produces  very  different  symptoms ;  injection  of  extracts  produces 
different  effects ;  moreover,  the  pituitary  contains  no  iodine,  therefore 
the  colloid  material  is  a  different  substance  in  the  two  cases. 

(3)  The  posterior  lobe. — This  is  connected  to  the  floor  of  the  third 
ventricle,  of  which  it  forms  a  developmental  outgrowth;  in  some 
animals  (cat)  it  remains  hollow  throughout  life,  in  others  (dog)  the 
neck  alone  remains  hollow,  and  in  most  (including  man)  both  body 
and  neck  are  solid,  with  traces  of  a  cavity  in  the  neck.  Though 
developed  from  the  brain,  it  contains  in  the  adult  no  nerve  cells,  but 
consists  mainly  of  neuroglia.  It  is  surrounded  and  invaded  by  the 
epithelium  cells  and  colloid  matter  derived  from  the  pars  intermedia. 
It  plays  the  part  of  a  brain  gland  in  virtue  of  these  epithelial  cells. 
What  the  use  of  the  secretion  into  the  third  ventricle  may  be  is  far 
from  clear.  P.  T.  Herring,  to  whom  we  owe  many  of  the  facts  already 
given,  suggests  that  disturbances  of  the  posterior  lobe  may  be 
responsible  for  the  diabetic  condition  so  frequently  seen  in  cases  of 
acromegaly.  Whether  this  is  so  or  not,  injections  of  aqueous 
extracts  :of  the  gland  have  pronounced  physiological  effects,  and 
these  may  be  boiled  without  losing  their  activity.  Although  we  do 
not  know  the  precise  nature  of  the  active  substance  (provisionally 
called  pituitrin)  in  the  posterior  lobe,  we  can  at  any  rate  say,  there- 
fore, that  it  is  not  protein. 

Intravenous  injection  of  such  extracts  produces : — 

1.  A  temporary  rise  of  arterial  blood-pressure ;  this  is  not  due  to 
the  presence  of  adrenaline,  for  a  second  injection  following  the  first 
produces  no  such  effect,  whereas  the  rise  of  pressure  produced  by 
adrenaline  may  be  repeated  time  after  time.     The  second  and  follow- 
ing injections  of  pituitary  extract,  unless  they  occur  at  much  pro- 
longed intervals,  produce  only  a  slight  fall  of  pressure,  which  is  the 
effect  produced  by  most  tissue  extracts.     The  rise  of  pressure  which 
occurs  at  the  first  injection  is,  however,  like  that  of  adrenaline,  pro- 
duced mainly  by  constriction  of  peripheral  arterioles.     Slowing  of  the 
heart  may  occasionally  also  be  produced.     Pituitrin  causes  also  con- 
traction of  other  forms  of  involuntary  muscle,  for  instance  the  uterus. 

2.  The  extract  has  a  specific  effect  on  the  kidney,  and  causes 


CH.  XXV.]  THE   PINEAL  GLAND  345 

there  not  constriction  but  dilatation  of  the  blood-vessels,  which 
persists  for  a  very  long  time.  Adrenaline,  on  the  other  hand,  con- 
stricts the  kidney  arterioles.  This  dilatation  is  accompanied  with 
pronounced  diuresis.  It  can  hardly  be  doubted  that  this  is  no  mere 
accident,  but  that  there  is  some  definite  relationship  between  the 
activity  of  the  posterior  lobe  of  the  pituitary  and  the  kidney 
function.  It  also  stimulates  milk  secretion  (Ott,  Schafer).  Extracts 
of  the  anterior  lobe  produce  neither  a  rise  of  blood-pressure  nor  any 
effect  upon  the  kidney  or  mammary  gland. 

The  pituitary  body  is  essential  for  life.  Paulesco,  and  later 
Harvey  Gushing  and  Horsley,  found  that  total  removal  of  the  organ 
is  fatal  in  a  few  days.  The  same  result  follows  entire  removal  of 
the  anterior  lobe.  On  the  other  hand,  removal  of  the  posterior  lobe 
produces  no  such  effect.  Partial  removal  of  the  anterior  lobe 
produces  a  condition  known  as  hypopituitarism,  in  which  adiposity 
accompanied  by  (or  secondary  to)  atrophy  of  the  organs  of  genera- 
tion are  the  most  marked  signs.  If  the  operation  is  done  before 
adolescence,  there  is  a  persistence  of  sexual  infantilism.  The  trans- 
plantation of  the  organ  from  another  animal,  or  injection  of  anterior 
lobe  extracts,  prolongs  the  life  of  animals  after  total  extirpation, 
or  relieves  the  symptoms  after  partial  extirpation.  In  many  of 
Horsley's  experiments  no  such  symptoms  occurred,  even  although 
only  minute  portions  of  the  anterior  lobe  were  left  behind. 

The  Pineal  Gland. 

This  gland,  which  is  a  small  reddish  body,  is  placed  beneath  the 
corpus  callosum,  and  rests  upon  the  corpora  quadrigemina.  It  is 
composed  of  tubes  and  saccules  lined  and  sometimes  filled  with 
epithelial  cells,  and  containing  deposits  of  earthy  salts  (brain  sand). 
A  few  small  atrophied  nerve-cells  without  axons  are  also  seen. 

In  certain  lizards,  such  as  Hatteria,  and  in  certain  fishes  such  as 
the  lamprey,  the  pineal  outgrowth  is  better  developed  and  may  be 
paired.  One  division  corresponds  to  the  pineal  gland;  the  other 
becomes  developed  into  an  eye-like  structure  connected  by  nerve- 
fibres  to  the  habenular  ganglion ;  this  third  eye  is  situated  centrally 
on  the  upper  surface  of  the  head,  but  is  covered  by  skin. 

The  Coccygeal  and  Carotid  Glands. 

These  are  situated,  the  one  in  front  of  the  tip  of  the  coccyx 
and  the  other  at  the  point  of  bifurcation  of  the  common  carotid 
artery.  They  are  made  up  of  a  plexus  of  small  arteries,  and 
are  enclosed  and  supported  by  fibrous  tissue.  They  contain  also 
polyhedral  cells  collected  into  spheroidal  clumps  (carotid  gland)  or 
irregular  nodules  (coccygeal  gland).  Some  of  the  cells  of  the 
carotid  gland  stain  brown  with  chromic  acid  like  those  of  the 
suprarenal  medulla. 


CHAPTEK   XXVI 

RESPIRATION 

THE  respiratory  apparatus  consists  of  the  lungs  and  of  the  air-passages 
which  lead  to  them.  In  marine  animals  the  gills  fulfil  the  same 
functions  as  the  lungs  of  air-breathing  animals.  The  muscles  which 
move  the  thorax  and  the  nerves  that  supply  them  must  also  be  in- 
cluded under  the  general  heading  Respiratory  System ;  and,  using 
this  expression  in  the  widest  sense,  it  includes  practically  all  the 
tissues  of  the  body,  since  they  are  all  concerned  in  the  using  up  of 
oxygen  and  the  production  of  waste  materials,  such  as  carbonic  acid. 

Essentially  a  lung  or  gill  is  constructed  of  a  thin  membrane,  one 
surface  of  which  is  exposed  to  the  air  or  water,  as  the  case  may  be, 
while,  on  the  other  is  a  network  of  blood-vessels — the  only  separation 
between  the  blood  and  aerating  medium  being  the  thin  wall  of  the 
blood-vessels,  and  the  fine  membrane  on  one  side  of  which  vessels  are 
distributed.  The  difference  between  the  simplest  and  the  most  com- 
plicated respiratory  membrane  is  one  of  degree  only. 

The  lungs  in  the  mammalia  are  only  the  medium  for  the  exchange, 
on  the  part  of  the  blood,  of  carbonic  acid  for  oxygen.  They  are  not 
the  seat,  in  any  special  manner,  of  those  combustion-processes  of 
which  the  production  of  carbonic  acid  is  the  final  result.  These 
processes  occur  in  all  parts  of  the  body  in  the  substance  of  the  tissues. 

The  Respiratory  Apparatus. 

The  lungs  are  contained  in  the  chest  or  thorax,  which  is  a  closed 
cavity  having  no  communication  with  the  outside  except  by  means  of 
the  respiratory  passages.  The  air  enters  these  passages  through  the 
nostrils  or  through  the  mouth,  whence  it  passes  through  the  larynx  into 
the  trachea  or  windpipe,  which  about  the  middle  of  the  chest  divides 
into  two  tubes,  bronchi,  one  to  each  (right  and  left)  lung. 

The  Larynx  is  the  upper  part  of  the  passage,  and  will  be  described 
in  connection  with  the  voice. 

846 


en.  XXVL] 


THE   TRACHEA 


347 


The  Trachea  and  Bronchi. — The  trachea  extends  from  the  cricoid 
cartilage,  which  is  on  a  level  with  the  fifth  cervical  vertebra,  to  a 


FIG.  2S3A. — Outline  showing  the  general  form 
of  the  larynx,  trachea,  and  bronchi,  as 
seen  from  the  front,  h,  The  great  cornu  of 
the  hyoid  bone  :  e,  epiglottis  ;  £,  superior, 
and  t',  inferior  cornu  of  the  thyroid  carti- 
lage ;  c,  middle  of  the  cricoid  cartilage ; 
tr,  the  trachea,  showing  sixteen  cartila- 
ginous rings ;  b,  the  right,  and  ?/,  the  left 
bronchus.  (Allen  Thomson.) 


Fio.  2S3B. — Outline  showing  the  general  form  of  the 
larynx,  trachea,  and  bronchi,  as  seen  from 
behind,  h,  Great  cormi  of  the  hyoid  bone ; 
t,  superior,  and  t',  the  inferior  cornu  of  the 
thyroid  cartilage  ;  c,  epiglottis  ;  a,  points  to  the 
back  of  both  the  arytenoid  cartilages,  which  are 
surmounted  by  t}ie  comicula ;  c,  the  middle 
ridge  on  the  back  of  the  cricoid  cartilage ;  tr,  the 
posterior  membranous  part  of  the  trachea ; 
?;,  ?/,  right  and  left  bronchi.  (Allen  Thomson.) 


point  opposite  the  third  dorsal  vertebra,  where  it  divides  into  the 
two  bronchi,  one  for  each  lung  (fig.  283).  It  measures,  in  man,  about 
four  or  four  and  a  half  inches  in  length  and  from  three-quarters  of 


348 


RESPIRATION 


[CH.  XXVI. 


an  inch  to  an  inch  in  diameter,  and  is  essentially  a  tube  of  fibro-elastic 
membrane,  within  the  layers  of  which  are  imbedded  a  series  of  carti- 
laginous rings,  from  sixteen  to  twenty  in  number.  These  rings  ex- 
tend only  around  the  front  and  sides  of  the  trachea  (about  two-thirds 
of  its  circumference)  and  are  deficient  behind;  the  interval  between 
their  posterior  extremities  is  bridged  over  by  a  continuation  of  the 
fibrous  membrane  in  which  they  are  enclosed  (fig.  28 SB).  The  inner 
surface  of  the  trachea  is  lined  with  ciliated  epithelium;  this, 

together  with  the  basement  mem- 
brane on  which  it  rests,  and  a 
deeper  layer  of  connective  tissue, 
forms  the  mucous  membrane  of 
the  trachea. 

Numerous  mucous   glands  are 
situated  in  the  substance  of   the 
mucous    membrane  ;    their   ducts 
perforate    the   various    structures 
which  form  the  wall  of  the  trachea, 
and  open  through  the  mucous  mem- 
brane into  the  interior.     A  layer 
of    unstriped   muscle    is    situated 
beneath    the    mucous    membrane 
at   the   back   of    the   tube   where 
the  cartilaginous  rings  are  absent. 
The  two  bronchi  into  which   the  trachea  divides,  resemble  the 
trachea  in  structure,  with  the   difference  that  in   them   there  is   a 
distinct  layer  of  unstriped  muscle  arranged  circularly  beneath  the 
mucous  membrane,  forming  the  muscularis  mucosce. 

The  bronchi  divide  and  subdivide,  in  the  substance  of  the  lungs, 
into  a  number  of  smaller  and  smaller  branches  (bronchial  tubes), 
which  penetrate  into  every  part  of  the  organ,  until  at  length  they 
end  in  the  smaller  subdivisions  of  the  lungs  called  lobules. 

All  the  larger  branches  have  walls  formed  of  fibrous  tissue,  con- 
taining portions  of  cartilaginous  rings,  by  which  they  are  held  open, 
and  unstriped  muscular  fibres,  as  well  as  longitudinal  bundles  of 
elastic  tissue.  They  are  lined  by  mucous  membrane  the  surface  of 
which,  like  that  of  the  trachea,  is  covered  with  ciliated  epithelium, 
but  the  several  layers  become  less  and  less  distinct  until  the  lining 
consists  of  a  single  layer  of  short  columnar  cells  covered  with  cilia 
(fig.  285).  The  mucous  membrane  is  abundantly  provided  with 
mucous  glands. 

As  the  subdivisions  become  smaller  and  smaller,  and  their  walls 
thinner,  the  cartilaginous  rings  become  scarcer  and  more  irregular, 
until,  in  the  smaller  bronchial  tubes,  they  are  represented  only  by 
minute  and  scattered  cartilaginous  flakes.  When  the  bronchial  tubes, 


FIG.  284. — Ciliated  epithelium  of  the  human 
trachea,  a,  Layer  of  longitudinally  arranged 
elastic  fibres ;  b,  basement  membrane ; 
c,  deepest  cells  circular  in  form ;  d,  inter, 
mediate  elongated  cells ;  e,  outermost  layer 
of  cells  fully  developed  and  bearing  cilia, 
x  350.  (Kolliker.) 


CH.  XXVI.]  THE    LUNGS    AND    PLEUILE  349 

by  successive  branchings,  are  reduced  to  about  ^  of  an  inch  ('6  mm.) 
in  diameter  they  lose  their  cartilaginous  element  altogether,  and  their 
walls  are  formed  only  of  a  fibrous  elastic  membrane  with  circular 
muscular  fibres;  they  are  still  lined,  however,  by  a  thin  mucous 
membrane  with  ciliated  epithelium,  the  length  of  the  cells  bearing 
the  cilia  having  become  so  far  diminished  that  the  cells  are  now 
cubical.  In  the  smaller  bronchial  tubes  the  muscular  fibres  are 
relatively  more  abundant  than  in  the  larger  ones,  and  form  a 
distinct  circular  coat. 

Most  of  the  structures  which  have  been  described  are  of  some 
clinical  importance.  The  secretion  of  the  mucous  glands,  for 
instance,  may  be  greatly  increased  in  the  condition  known  as  catarrh 
of  the  mucous  membrane.  The  secretion,  or  phlegm,  is  worked  up  to 


s.rn 


FIG.  285. — Transverse  section  of  a  bronchial  tube,  about  £  inch  in  diameter,  e,  Epithelium  (ciliated), 
immediately  beneath  it  is  the  corium  of  the  mucous  membrane,  of  varying  thickness  ;  m,  muscular 
layer;  s.w,  submucous  tissue;  /,  fibrous  tissue;  c,  cartilage  enclosed  within  the  layers  of  fibrous 
tissue ;  g,  mucous  glands.  (F.  E.  Schulze.) 

the  larynx  by  the  ciliated  epithelium.  Its  presence  irritates  the 
very  sensitive  surface  of  that  organ,  and  induces  a  cough  by  which 
the  phlegm  is  expelled  from  the  respiratory  passages  into  the 
mouth. 

The  whole  inner  surface  of  the  bronchi  may  become  inflamed 
and  filled  with  fluid,  through  which  the  air  has  to  be  forced  at  each 
respiration  (bronchitis). 

A  disorder  of  another  nature,  bronchial  asthma,  is  caused  by 
undue  contraction  of  the  circular  muscles  of  the  bronchi.  The 
passages  are  thus  rendered  too  narrow  for  the  necessary  volume  of 
air  to  pass  conveniently,  and  as  a  result  the  respiration  becomes 
forced.  The  bronchial  muscles  are  supplied  by  the  vagus  nerve,  and 
relaxation  of  them  may  be  brought  about  by  drugs  which  prevent 
the  passage  of  impulses  along  the  vagus. 

The  Lungs  and  Pleurae. — The  lungs  occupy  the  greater  portion  of 


350  RESPIRATION  [CH.  XXVI. 

the  thorax.  They  are  of  a  spongy  elastic  texture,  and  are  composed 
of  numerous  minute  air-sacs,  and  on  section  every  here  and  there  the 
air-tubes  may  be  seen  cut  across.  Any  fragment  of  lung  (unless 
from  a  child  that  has  never  breathed,  or  in  cases  of  disease  in  which 
the  lung  is  consolidated  by  inflammation  or  pneumonia)  floats  in 
water ;  no  other  tissue  (except  fat)  does  this. 

Each  lung  is  enveloped  by  a  serous  membrane — the  pleura,  one 
layer  of  which  adheres  closely  to  its  surface,  and  provides  it  with  its 
smooth  and  slippery  covering,  while  the  other  adheres  to  the  inner 
surface  of  the  chest-wall.  The  continuity  of  the  two  layers,  which 
form  a  closed  sac,  as  in  the  case  of  other  serous  membranes,  will  be 
best  understood  by  reference  to  fig.  286.  The  appearance  of  a  space, 
however,  between  the  pleura  which  covers  the  lung  (visceral  layer) 


FIG.  286. — Transverse  section  of  the  chest. 

and  that  which  lines  the  inner  surface  of  the  chest  (parietal  layer) 
is  inserted  in  the  drawing  only  for  the  sake  of  distinctness.  It  does 
not  really  exist.  The  layers  are,  in  health,  everywhere  in  contact 
one  with  the  other;  and  between  them  is  only  just  so  much  fluid  as 
will  ensure  the  lungs  gliding  easily,  in  their  expansion  and  contrac- 
tion, on  the  inner  surface  of  the  parietal  layer,  which  lines  the  chest- 
wall. 

If,  however,  an  opening  is  made  so  as  to  permit  air  or  fluid  to 
enter  the  pleural  sac,  the  lung,  in  virtue  of  its  elasticity,  recoils,  and 
a  considerable  space  is  left  between  it  and  the  chest-wall.  In  other 
words,  the  natural  elasticity  of  the  lungs  would  cause  them  at  all 
times  to  contract  away  from  the  ribs  were  it  not  that  the  contraction 
is  resisted  by  atmospheric  pressure  which  bears  only  on  the  inner 
surface  of  the  air-tubes  and  air-sacs.  On  the  admission  of  air  into 
the  pleural  sac,  atmospheric  pressure  bears  alike  on  the  inner  and 


CH.  XXVL] 


THE   LUNGS 


351 


outer  surfaces  of  the  lung,  and  their  elastic  recoil  is  no  longer 
prevented. 

The  pleura,  like  other  serous  sacs,  is  frequently  the  scat  of  intlam- 
matory  changes  (pleurisy) ;  the  pleural  cavity  then  becomes  enlarged 
by  an  increase  in  the  amount  of  fluid  lymph  which  it  contains.  The 
increase  is  accompanied  by  corresponding  collapse  of  the  lungs.  A 
formation  of  fibrin  may  take  place  in  the  exuded  fluid ;  this  adheres 
to  the  pleura  and  causes  its  surfaces,  originally  smooth,  to  become 
rough,  and  painful  friction  between  the  two  surfaces,  or  even  their 
adhesion  to  one  another,  may  supervene. 

Each  lung  is  partially  subdivided  into  separate  portions  called 
lobes ;  the  right  lung  into  three  lobes,  and  the  left  into  two.  Each 
of  these  lobes,  again,  is  composed  of  a 
large  number  of  minute  parts,  called 
lobules.  Each  pulmonary  lobule  may 
be  considered  to  be  a  lung  in  minia- 
ture, consisting,  as  it  does,  of  a 
branch  of  the  bronchial  tube,  of  air- 
sacs,  blood-vessels,  nerves,  and  lym- 
phatics, with  a  sparing  amount  of 
areolar  tissue. 

On  entering  a  lobule,  the  small 
bronchial  tube,  the  structure  of 
which  has  just  been  described 
(fig.  287)  divides  and  subdivides; 
its  walls  at  the  same  time  become 
thinner  and  thinner,  until  at 
length  they  are  formed  only  of  a 
thin  membrane  of  areolar,  muscular, 
and  elastic  tissue,  lined  by  a  layer 
of  pavement  epithelium  not  pro- 
vided with  cilia.  At  the  same 
time  they  are  altered  in  shape ;  each 

of  the  minute  terminal  branches  widens  out  funnel-wise,  and  its 
walls  are  pouched  out  irregularly  into  small  saccular  dilatations, 
called  air-sacs.  Such  a  funnel-shaped  terminal  branch  of  the 
bronchial  tube,  with  its  group  of  pouches  or  air-sacs,  is  called  an 
infundibulum,  and  the  irregular  oblong  space  in  its  centre,  with 
which  the  air-sacs  communicate,  an  intercellular  passage. 

The  air-sacs,  or  air-vesicles,  may  be  placed  singly,  like  recesses 
from  the  intercellular  passage,  but  more  often  they  are  arranged  in 
groups,  or  even  in  rows,  like  minute  sacculated  tubes ;  so  that  a  short 
series  of  vesicles,  all  communicating  with  one  another,  open  by  a 
common  orifice  into  the  tube.  The  vesicles  are  of  various  forms, 
according  to  the  mutual  pressure  to  which  they  are  subject ;  their 


FIG.  287. — Two  small  infundibula  or  groups 
of  air-sacs,  a  a,  with  air-sacs,  b  b,  and  the 
ultimate  bronchial  tubes,  c  c,  with  which 
the  air-sacs  communicate.  From  a  new- 
born child.  (Kolliker.) 


352 


RESPIRATION 


[CH.  XXYI. 


walls  are  nearly  in  contact,  and  they  vary  from  -^th  to  TVth  of  an 
inch  ('5  to  *3  mm.)  in  diameter.  Their  walls  are  formed  of  fine 
membrane,  like  those  of  the  intercellular  passage;  this  membrane 
is  folded  on  itself  so  as  to  form  a  sharp-edged  border  at  each  circular 
orifice  of  communication  between  contiguous  air-vesicles,  or  between 
the  vesicles  and  the  bronchial  passages.  Numerous  fibres  of  elastic 
tissue  are  spread  out  between  contiguous  air-sacs,  and  many  of  these 
are  attached  to  the  outer  surface  of  the  fine  membrane  of  which  each 
sac  is  composed,  imparting  to  it  additional  strength  and  the  power  of 
recoil  after  distension.  The  vesicles  are  lined  by  a  layer  of  pavement 
epithelium  (fig.  288).  Outside  the  air-vesicles  a  network  of  pulmonary 


FIG.  288.— Section  of  lung  stained  with  silver  nitrate.  A.  D.,  alveolar  duct  or  intercellular  passage ; 
S,  alveolar  septa;  N,  alveoli  or  air-sacs,  lined  with  large  flat  cells,  with  some  smaller  polyhedral 
cells  ;  M,  plain  muscular  fibres  surrounding  the  alveolar  duct.  (Klein  and  Noble  Smith.) 

capillaries  is  spread  out  so  densely  (fig.  289)  that  the  interspaces  or 
meshes  are  even  narrower  than  the  vessels,  which  are,  on  an  average, 
ainnrth  of  an  inch  (8  /uC)  in  diameter.  Between  the  air  in  the  sacs 
and  the  blood  in  these  vessels  nothing  intervenes  but  the  thin  walls 
of  the  air-sacs  and  of  the  capillaries ;  and  the  exposure  of  the  blood 
to  the  air  is  the  more  complete,  because  the  folds  of  membrane 
between  contiguous  air-sacs,  and  often  the  spaces  between  the  walls 
of  the  same,  contain  only  a  single  layer  of  capillaries,  both  sides  of 
which  are  thus  at  once  exposed  to  the  air.  The  arrangement  of  the 
capillaries  is  shown  on  a  larger  scale  in  fig.  205  (p.  223). 

Area  of  the  Surface  of  the  Lung. — The  object  of  the  compli- 
cated structure  of  the  lung  is  to  provide  a  very  large  surface,  for  the 


CH.  XXVI.]  BLOOD-SUPPLY  OF  THE   LUNGS  353 

interchange  of  gases,  in  a  compact  organ.  The  total  surface  of  the 
inside  of  the  lung  has  been  variously  calculated,  but  it  may  be  taken 
to  be  about  90  square  metres  in  the  adult,  or  about  the  size  of  a 
carpet  necessary  to  cover  the  floor  of  a  good-sized  room  (10  yards 
by  12). 

The  vesicles  of  adjacent  lobules  do  not  communicate;  so  that, 
when  any  bronchial  tube  is  closed  or  obstructed,  the  supply  of  air  is 
lost  for  all  the  sacs  opening  into  it  or  its  branches. 

Blood-supply. — The  lungs  receive  blood  from  two  sources,  (a)  the 
pulmonary  artery,  (b)  the  bronchial  arteries.  The  former  conveys 
venous  blood  to  the  lungs  to  be  arterialised.  The  branches  of  the 
bronchial  arteries  convey  arterial  blood  from  the  aorta  for  the 


FIG.  289. — Capillary  network  of  the  pulmonary  blood-vessels  in  the  human  lung. 
X  60.    (Kolliker.) 

nutrition  of  the  walls  of  the  bronchi,  of  the  larger  pulmonary  vessels, 
of  the  interlobular  connective  tissue,  etc. ;  the  blood  of  the  bronchial 
vessels  is  returned  chiefly  through  the  bronchial  and  partly  through 
the  pulmonary  veins. 

Lymphatics. — The  lymphatics  consist  of  irregular  lacunre  in  the 
walls  of  the  air-sacs,  in  the  walls  of  the  bronchial  tubes,  and  in  the 
pulmonary  pleura.  The  lymphatic  vessels  from  all  these  irregular 
sinuses  pass  in  towards  the  root  of  the  lung  to  reach  the  bronchial 
lymphatic  glands. 

Nerves. — The  nerves  of  the  lung  contained  in  the  anterior  and 
posterior  pulmonary  plexuses  are  formed  by  branches  of  the  vagus 
and  sympathetic.  They  follow  the  course  of  the  vessels  and  bronchi, 
and  in  the  walls  of  the  latter  many  small  ganglia  are  situated. 


354  RESPIRATION  [OH.  XXTI. 


The  Respiratory  Mechanism. 

Kespiration  consists  of  the  alternate  expansion  and  contraction 
of  the  thorax,  by  means  of  which  air  is  drawn  into  or  expelled 
from  the  lungs.  These  acts  are  called  Inspiration  and  Expiration 
respectively. 

For  the  inspiration  of  air  into  the  lungs  a  movement  of  the  side- 
walls  and  floor  of  the  chest  takes  place,  so  that  the  capacity  of  the 
interior  is  enlarged.  By  such  increase  of  capacity  there  will  be  a 
diminution  of  the  pressure  of  the  air  in  the  lungs,  and  a  fresh 
quantity  will  enter  through  the  larynx  and  trachea  to  equalise  the 
pressure  on  the  inside  and  outside  of  the  chest. 

For  the  expiration  of  air,  the  opposite  movement  diminishes  the 
capacity  of  the  chest;  the  pressure  in  the  interior  will  be  thus 
increased,  and  air  will  be  expelled,  until  the  pressure  within  and 
without  the  chest  are  again  equal.  In  both  cases  the  air  passes 
through  the  trachea,  there  being  no  other  communication  with  the 
exterior  of  the  body ;  and  the  lung  remains,  under  all  circumstances, 
closely  in  contact  with  the  walls  and  floor  of  the  chest.  The  move- 
ments of  the  lung  are  therefore  passive,  not  active,  and  depend  on 
the  changes  of  shape  of  the  closed  cavity  in  which  they  are  contained. 
A  perforation  of  the  chest-wall  would  mean  that  the  lung  on  that 
side  would  no  longer  be  of  use ;  a  similar  injury  on  the  other  side 
(double  pneumothorax)  would  cause  death.  If  the  two  layers  of  the 
pleura  were  adherent,  those  portions  of  the  lung  would  be  expanded 
most  where  the  movements  of  the  chest  are  greatest.  The  existence 
of  the  two  layers  prevents  this,  and  thus  the  lung  is  equally  expanded 
throughout. 

Inspiration. — This  is  a  muscular  act ;  the  effect  of  the  action  of 
the  inspiratory  muscles  is  an  increase  in  the  size  of  the  chest-cavity 
in  the  vertical,  the  lateral,  and  antero-posterior  diameters. 

The  vertical  diameter  of  the  chest  is  increased  by  the  contraction 
and  consequent  descent  of  the  diaphragm ;  at  rest,  the  diaphragm  is 
dome-shaped  with  the  convexity  upwards ;  the  central  tendon  forms 
a  slight  depression  in  the  middle  of  this  dome.  On  contraction  the 
muscular  fibres  shorten,  and  so  the  convexity  of  the  double  dome  is 
lessened.  The  central  tendon  is  drawn  down  a  certain  distance,  but 
the  chief  movement  is  at  the  sides.  For  the  effective  action  of  this 
muscle,  its  attachment  to  the  lower  ribs  is  kept  fixed  by  the  con- 
traction of  the  quadratus  lumborum.  The  diaphragm  is  supplied  by 
the  phrenic  nerves. 

The  increase  in  the  lateral  and  antero-posterior  diameters  of  the 
chest  is  effected  by  the  raising  of  the  ribs,  the  upper  ones  being  fixed 


CH.  XXVI.]  MUSCLES    OF   RESPIRATION  355 

by  the  scaleni.  The  greater  number  of  the  ribs  are  attached  very 
obliquely  to  the  spine  and  sternum. 

The  elevation  of  the  ribs  takes  place  both  in  front  and  at  the 
sides — the  hinder  ends  being  prevented  from  performing  any  upward 
movement  by  their  attachment  to  the  spine.  The  movement  of- 
the  front  extremities  of  the  ribs  is  of  necessity  accompanied  by 
an  upward  and  forward  movement  of  the  sternum  to  which  they 
are  attached,  the  movement  being  greater  at  its  lower  than  at  its 
upper  end. 

The  muscles  by  which  the  ribs  are  raised,  in  ordinary  quiet  inspira- 
tion, are  the  external  intercostals,  and  that  portion  of  the  internal 
intercostals  which  is  situated  between  the  costal  cartilages;  and 
these  are  assisted  by  the  levatores  costarum,  and  the  serratus  posticus 
superior. 

In  extraordinary  or  forced  inspiration,  additional  muscles  are 
pressed  into  service,  such  as  the  sternomastoid,  the  serratus  magnus, 
the  pectorales,  and  the  trapezius.  Laryngeal  and  face  muscles  also 
come  into  play. 

The  expansion  of  the  chest  in  inspiration  presents  some  peculi- 
arities in  different  persons.  In  young  children,  it  is  effected  chiefly 
by  the  diaphragm.  The  movement  of  the  abdominal  walls  being  here 
more  manifest  than  that  of  any  other  part,  it  is  usual  to  call  this  the 
abdominal  type  of  respiration.  In  men,  together  with  the  descent  of 
the  diaphragm,  and  the  pushing  forward  of  the  front  wall  of  the 
abdomen,  the  chest  and  the  sternum  are  subject  to  a  wide  movement 
in  inspiration  (inferior  costal  type).  In  women,  the  movement 
appears  less  extensive  in  the  lower,  and  more  so  in  the  upper,  part  of 
the  chest  (superior  costal  type). 

Expiration. — From  the  enlargement  produced  in  inspiration,  the 
chest  and  lungs  return,  in  ordinary  tranquil  expiration,  by  their 
elasticity  to  their  previous  condition;  the  force  employed  by  the 
inspiratory  muscles  in  distending  the  chest  and  overcoming  the 
elastic  resistance  of  the  lungs  and  chest-walls,  is  returned  as  an 
expiratory  effort  when  the  muscles  are  relaxed.  This  elastic  recoil 
of  the  chest  and  lungs  is  sufficient,  in  ordinary  quiet  breathing,  to 
expel  air  from  the  lungs  in  the  intervals  of  inspiration,  and  no 
muscular  power  is  required.  In  all  voluntary  expiratory  efforts, 
however,  as  in  speaking,  singing,  blowing,  and  the  like,  and  in  many 
involuntary  actions  also,  as  sneezing,  coughing,  etc.,  something  more 
than  merely  passive  elastic  power  is  necessary,  and  the  proper 
expiratory  muscles  are  brought  into  action.  The  chief  of  these  are 
the  abdominal  muscles,  which,  by  pressing  on  the  viscera  of  the 
abdomen,  push  up  the  floor  of  the  chest  formed  by  the  diaphragm, 
and  by  thus  making  pressure  on  the  lungs,  expel  air  from  them 
through  the  trachea  and  larynx.  All  muscles,  however,  which  depress 


356  RESPIRATION  [CH.  XXVI. 

the  ribs,  must  act  also  as  muscles  of  expiration,  and  therefore  we  must 
conclude  that  the  abdominal  muscles  are  assisted  in  their  action  by 
the  interosseous  part  of  the  internal  inter costals,  the  triangularis  sterni, 
the  serratus  posticus  inferior,  and  quadratus  lumlorum.  When  by 
the  efforts  of  the  expiratory  muscles,  the  chest  has  been  squeezed  to 
less  than  its  average  size,  it  again,  on  relaxation  of  the  muscles, 
returns  to  the  normal  dimensions  by  virtue  of  its  elasticity.  The 
construction  of  the  chest-walls,  therefore,  admirably  adapts  them  for 
recoiling  against  and  resisting  undue  contraction  as  well  as  undue 
dilatation. 

Graphic  Record  of  Respiratory  Movements. 

Among  numerous  methods  which  have  been  described  for  record- 
ing the  respiratory  movements  the  simplest  in  the  case  of  the  human 


FIQ.  290. — Stethograph  tracings  from  the  human  subject.    Each  upstroke  is  due  to  inspiration ;  each 
downstroke  to  expiration.     The  lowest  line  is  a  time-tracing  marking  half-seconds. 

subject,  especially  if  he  be  a  patient  in  bed,  is  to  fasten  a  bandage 
loosely  round  the  chest.  Between  the  bandage  and  the  chest-wall  a 
flexible  hollow  rubber  ball  is  placed.  This  ball  communicates  by  a 
rubber  tube  with  a  recording  tambour.  All  such  appliances  are 


CH.  XXVI.] 


GRAPHIC   RECORD 


RESPIRATlOMS 


3o7 


called  Stethographs.  In  tracings  taken  with  a  stethograph  applied  to 
the  chest-wall  of  man  or  animals,  the  large  up-and-down  strokes  due 
to  respiration  have  smaller  tremors  upon  them,  due  to  the  heart- 
beats. 

The  tracings  in  fig.  290  were  obtained  by  applying  a  stetho- 
graph to  a  man's  chest.  During  the  tracing  shown  at  the  top,  he 
was  breathing  quietly ;  during  the  tracing  shown  on  the  next  line, 
he  was  breathing  deeply. 

It  is  also  possible  to  record  the  diaphragmatic  movements  by  the 
insertion  of  an  elastic  bag  connected  with  a  tambour  into  the 


FIG.  291.— Tracing  of  the  normal  diaphragm  respirations  of  rabbit,  a,  With  quick  movement  of  drum  ; 
b,  with  slow  movement.  The  upstrokes  represent  inspiration ;  the  downstrokes,  expiration.  To 
be  read  from  left  to  right.  The  time  tracing  in  each  case  represents  seconds.  (Marckwald.) 

abdomen  below  it  (plirenograpJi),  by  the  insertion  of  needles  into 
different  parts  of  its  structure,  or  by  recording  the  contraction  of 
isolated  strips  of  the  diaphragm.  Such  a  strip  attached  in  the 
rabbit  to  the  xiphisternal  cartilage  may  be  detached,  and  attached 
by  a  thread  to  a  recording  lever ;  this  strip  serves  as  a  sample  of  the 
diaphragm 

Fig.  291  shows  a  tracing  obtained  in  this  way. 

The  variations  of  intrapleural  pressure  may  be  recorded  by  the 
introduction  of  a  cannula  into  the  pleural  cavity,  which  is  connected 
with  a  mercurial  manometer. 

The  act  of  inspiring  air,  especially  in  women  and  children,  is  a 
little  shorter  than  that  of  expelling  it,  and  there  is  commonly  a  very 


358  RESPIRATION  [OH.  XXVI. 

slight  pause  between  the  end  of  expiration  and  the  beginning  of  the 
next  inspiration. 

If  the  ear  is  placed  in  contact  with  the  wall  of  the  chest,  or  is 
separated  from  it  only  by  a  good  conductor  of  sound  or  stethoscope, 
a  faint  respiratory  or  vesicular  murmur  is  heard  during  inspiration. 
This  sound  varies  somewhat  in  different  parts — being  loudest  or 
coarsest  in  the  neighbourhood  of  the  trachea  and  large  bronchi 
(tracheal  and  bronchial  breathing),  and  fading  off  into  a  faint  sighing 
as  the  ear  is  placed  at  a  distance  from  these  (vesicular  breathing).  It 
is  bast  heard  in  children,  and  in  them  a  faint  murmur  is  heard  in  ex- 
piration also.  The  cause  of  the  vesicular  murmur  has  received  various 
explanations  ;  but  most  observers  hold  that  the  sound  is  produced  by 
the  air  passing  through  the  glottis  and  larger  tubes,  and  that  this 
sound  is  modified  in  its  conduction  through  the  substance  of  the  lung. 
The  alterations  in  the  normal  breath  sounds,  and  the  various  additions 
to  them  that  occur  in  different  diseased  conditions,  can  only  be 
properly  studied  at  the  bedside. 

During  the  action  of  the  muscles  which  directly  draw  air  into 
the  chest,  those  which  guard  the  opening  through  which  it  enters  are 
not  passive.  In  hurried  breathing  the  instinctive  dilatation  of  the 
nostrils  is  well  seen,  although  under  ordinary  conditions  it  may  not 
be  noticeable.  The  opening  at  the  upper  part  of  the  larynx  or  rima 
glottidis  is  slightly  dilated  at  each  inspiration  for  the  more  ready 
passage  of  air,  and  becomes  smaller  at  each  expiration  ;  its  condition, 
therefore,  corresponds  during  respiration  with  that  of  the  walls  of 
the  chest.  There  is  a  further  likeness  between  the  two  acts  in  that, 
under  ordinary  circumstances,  the  dilatation  of  the  rima  glottidis  is 
a  muscular  act  and  its  narrowing  chiefly  an  elastic  recoil. 

Terms  used  to  express  Quantity  of  Air  breathed. — a.  Tidal 
air  is  the  quantity  of  air  which  is  habitually  and  almost  uniformly 
changed  in  each  act  of  breathing.  In  a  healthy  adult  man  it  averages 
about  500  c.c.,  or  rather  more  than  30  cubic  inches,  according  to  the 
recent  measurements  made  by  Haldane.  This  will  be  expanded  at 
body  temperature  to  600  c.c.  This  amount  of  air  is  not  sufficient 
to  fill  the  lungs.  Haldane  gives  the  capacity  of  the  upper 
air-passages  and  bronchial  tubes  as  200  c.c.,  and  therefore  about 
a  third  of  the  tidal  air  is  required  to  fill  this  dead  space.  At 
the  end  of  an  expiration,  however,  the  tubes  and  alveoli  are  not 
empty  of  air,  and  the  sudden  inrush  of  atmospheric  air  during 
the  next  inspiration  effects  a  complete  mixture  of  this  air  with 
that  left  in  the  air-passages;  the  air  in  the  axial  stream  of  the 
current  will  penetrate  as  far  as  the  alveoli,  but  what  is  sucked  into 
the  alveoli  is  mainly  some  of  the  mixture  from  the  bronchial  passages, 
and  that  in  turn  is  derived  from  the  mixture  (containing  more  atmos- 
pheric air  in  proportion)  in  the  upper  air-cavities.  During  expiration 


CH.  XXVI.]  TIDAL  AIR  359 

the  air  which  leaves  the  lungs  will  come  in  part  from  the  alveoli,  but 
the  effect  of  the  stream  of  outgoing  air  is  mainly  as  before,  to  effect  a 
thorough  admixture  of  the  air  in  the  intermediate  air-passages  ;  thus 
the  alveolar  air  will  become  mixed  with  that  in  the  bronchial  tubes, 
and  that  in  turn  will  be  mixed  with  that  in  the  upper  air-chambers. 
In  a  succession  of  alternate  ordinary  inspirations  and  expirations 
adequate  ventilation  is  secured,  but  obviously  the  composition  of  the 
expired  air  is  not  the  same  as  that  of  alveolar  air,  for  the  latter, 
though  it  is  ultimately  breathed  out,  is  diluted  on  its  upward  journey 
by  mixture  with  the  bronchial  air,  and  that  in  its  turn  with  the  air 
of  the  upper  air-chambers ;  in  other  words,  the  expired  air  is  alveolar 
air  (rich  in  carbon  dioxide)  diluted  with  bronchial  air  (richer  in 
oxygen)  and  with  atmospheric  air  (still  richer  in  oxygen). 

b.  Complemental  air  is  the  quantity  over  and  above  this  which 
can    be    drawn    into    the   lungs   in    the    deepest   inspiration ;    its 
amount  averages  100  cubic  inches,  or  about  1600  c.c. 

c.  Reserve  or  supplemental  air. — After  an  ordinary  expiration,  such 
as  that  which  expels  the  tidal  air,  a  further  quantity  of  air,  about  100 
cubic  inches  (1600  c.c.)  can  be  expelled  by  a  forcible  deep  expiration. 
This  is  termed  reserve  or  supplemental  air.     The  last  portion  of  the 
air  thus  expelled  will  consist  of  air  from  the  alveoli. 

d.  Residual  air  is  the  quantity  which  still  remains  in  the  lungs 
after  the  most  violent  expiratory  effort.     Its  amount  depends  in  great 
measure  on  the  absolute  size  of  the  chest,  but  may  be  estimated  at 
about  100  cubic  inches,  or  about  1600  c.c. 

The  total  quantity  of  air  which  passes  into  and  out  of  the  lungs 
of  an  adult,  at  rest,  in  24  hours,  varies  from  400,000  (Marcet)  to 
680,000  (Hutchinson)  cubic  inches.  This  quantity,  however,  is 
increased,  and  may  be  more  than  doubled  by  exertion. 

e.  Respiratory  or  Vital  Capacity. — The  vital  capacity  of  the  chest 
is  indicated  by  the  quantity  of  air  which  a  person  can  expel  from  his 
lungs  by  a  forcible  expiration  after  the  deepest  inspiration  possible. 
The  average  capacity  of  an  adult,  at  15'4°  C.  (60°  F.),  is  about  225  to 
250  cubic  inches,  or  3500  to  4000  c.c.     It  is  the  sum  of  the  com- 
plemental,  tidal,  and  supplemental  air. 

The  respiratory  capacity,  or  as  John  Hutchinson  called  it,  vital  capacity,  is 
usually  measured  by  a  modified  gasometer  or  spirometer,  into  which  the  experi- 
menter breathes, — making  the  most  prolonged  expiration  possible  after  the  deepest 
possible  inspiration.  The  quantity  of  air  which  is  thus  expelled  from  the  lungs  is 
indicated  by  the  height  to  which  the  air-chamber  of  the  spirometer  rises  ;  and  by 
means  of  a  scale  placed  in  connection  with  this,  the  number  of  cubic  inches  is  read 
off.  Haldane  measures  the  volume  of  air  expired  by  the  reduction  which  takes 
place  in  the  volume  of  the  body  when  placed  within  a  plethysmograph  large 
enough  to  take  a  man,  with  the  exception  of  his  head. 

The  number  of  respirations  in  a  healthy  adult  person  usually  ranges 
from  14  to  18  per  minute.  It  is  greater  in  infancy  and  childhood. 


360  RESPIRATION  [CH.  XXTI. 

It  varies  also  much  according  to  different  circumstances,  such  as 
exercise  or  rest,  health  or  disease,  etc.  Variations  in  the  number  of 
respirations  correspond  ordinarily  with  similar  variations  in  the 
pulsations  of  the  heart.  In  health  the  proportion  is  about  1  to  4, 
or  1  to  5,  and  when  the  rapidity  of  the  heart's  action  is  increased, 
that  of  the  chest  movement  is  commonly  increased  also ;  but  not  in 
every  case  in  equal  proportion.  It  happens  occasionally  in  disease, 
especially  of  the  lungs  or  air-passages,  that  the  number  of  respiratory 
acts  increases  in  quicker  proportion  than  the  beats  of  the  pulse  ;  and, 
in  other  affections,  much  more  commonly,  that  the  number  of  the 
pulse-beats  is  greater  in  proportion  than  that  of  the  respirations. 

The  Force  of  Inspiratory  and  Expiratory  Muscles. — The  force  with 
which  the  inspiratory  muscles  are  capable  of  acting  is  greatest  in 
individuals  of  the  height  of  from  five  feet  seven  inches  to  five  feet 
eight  inches,  and  will  elevate  a  column  of  nearly  three  inches  (about 
60  mm.)  of  mercury.  Above  this  height  the  force  decreases  as  the 
stature  increases ;  so  that  the  average  of  men  of  six  feet  can  elevate 
only  about  two  and  a  half  inches  of  mercury.  The  force  manifested 
in  the  strongest  expiratory  acts  is,  on  the  average,  one-third  greater 
than  that  exercised  in  inspiration.  But  this  difference  is  in  great 
measure  due  to  the  power  exerted  by  the  elastic  reaction  of  the  walls 
of  the  chest ;  and  it  is  also  much  influenced  by  the  disproportionate 
strength  which  the  expiratory  muscles  attain,  from  their  being  called 
into  use  for  other  purposes  than  that  of  simple  expiration.  The  force 
of  the  inspiratory  act  is,  therefore,  better  adapted  than  that  of  the 
expiratory  for  testing  the  muscular  strength  of  the  body.  (John 
Hutchinson.) 

In  ordinary  quiet  breathing,  there  is  a  negative  pressure  of  only 
1  mm.  during  inspiration,  and  a  positive  pressure  of  from  2  to  3  mm. 
mercury  during  expiration. 

The  instrument  used  by  Hutchinson  to  gauge  the  inspiratory  and  expiratory 
power  was  a  mercurial  manometer,  to  which  was  attached  a  tube  fitting  the  nostrils, 
and  through  which  the  inspiratory  or  expiratory  effort  was  made. 

The  greater  part  of  the  force  exerted  in  deep  inspiration  is 
employed  in  overcoming  the  resistance  offered  by  the  elasticity  of 
the  lungs. 

In  man  the  pressure  exerted  by  the  elasticity  of  the  lungs  alone  is 
about  6  mm.  of  mercury.  This  is  estimated  by  tying  a  manometer 
into  the  trachea  of  a  dead  subject,  and  observing  the  rise  of  mercury 
that  occurs  on  puncture  of  the  chest-walls.  If  the  chest  is  distended 
beforehand  so  as  to  imitate  a  forcible  inspiration,  a  much  larger  rise 
(30  mm.)  of  the  mercury  is  obtained.  During  life  this  elastic  force 
is  assisted  by  the  contraction  of  the  plain  muscular  fibres  of  the 
alveoli  and  bronchial  tubes,  the  pressure  of  which  probably  does  not 
exceed  1  or  2  mm.  Hutchinson  calculated  that  the  total  force  to  be 


CH.  XXVI.]  THE  GASES  OF  THE  BLOOD  361 

overcome  by  the  muscles  in  the  act  of  inspiring  200  cubic  inches  of 
air  is  more  than  450  Ibs. 

It  is  possible  that  the  contractile  power  which  the  bronchial  tubes 
and  air-vesicles  possess,  by  means  of  their  muscular  fibres,  may  assist 
in  expiration ;  but  it  is  more  likely  that  the  chief  purpose  of  this 
muscular  tissue  is  to  regulate  and  adapt,  in  some  measure,  the 
quantity  of  air  admitted  to  the  lungs,  and  to  each  part  of  them, 
according  to  the  supply  of  blood :  the  muscular  tissue  also  contracts 
upon  and  gradually  expels  collections  of  mucus,  which  may  have 
accumulated  within  the  tubes,  and  which  cannot  be  ejected  by  forced 
expiratory  efforts,  owing  to  collapse  or  other  morbid  conditions  of  the 
portion  of  lung  connected  with  the  obstructed  tubes  (Gairdner). 

The  Gases  of  the  Blood. 

Before  the  student  can  study  either  the  chemistry  of  respiration 
or  its  regulation,  which  is  in  part  a  chemical  process,  it  is  necessary 
that  he  should  have  an  adequate  conception  of  the  fundamental  laws 
which  regulate  the  retention  of  oxygen  and  carbonic  acid  in  the 
blood ;  and  as  the  blood  presents  many  complications,  it  will  be  best 
at  the  outset  to  consider  the  solution  of  gases  in  such  a  simple 
medium  as  water. 

Solution  of  Gases  in  Water. 

If  water  is  shaken  up  with  oxygen,  a  certain  definite  amount  of 
oxygen  will  become  dissolved  in  the  water.  Under  the  same  condi- 
tions the  same  quantity  of  oxygen  would  always  be  dissolved,  and  in 
the  following  argument  it  is  assumed  throughout  that  the  tempera- 
ture remains  constant.  The  amount  dissolved  depends  then  upon  two 
circumstances,  each  of  which  can  be  measured.  The  first  is  the 
pressure  of  the  oxygen  to  which  the  water  is  exposed  when  shaken ; 
the  second  is  a  property  of  the  oxygen  itself,  namely,  its  solubility 
in  water.  The  solubilities  of  different  gases  differ  very  much ;  some 
(for  instance,  oxygen)  are  not  readily  soluble  in  water,  whilst  others, 
such  as  carbonic  acid,  are  very  soluble. 

If  a  cubic  centimetre  of  water  was  introduced  into  a  large  air- 
tight bottle  containing  pure  oxygen  at  the  atmospheric  pressure,  and 
another  cubic  centimetre  of  water  was  similarly  placed  in  a  bottle 
containing  pure  carbonic  acid  at  the  same  pressure,  the  former  would 
be  found  to  have  dissolved  0-04  c.c.  of  oxygen,  the  latter  1  c.c.  of 
carbonic  acid.  These  figures  represent  the  degrees  to  which  the 
two  gases  are  soluble  in  water  under  similar  circumstances,  and 
are  called  their  coefficients  of  solubility.  The  coefficient  of  solu- 
bility of  gas  in  a  liquid  is  therefore  the  volume  of  gas  which  1  c.c. 
of  the  liquid  will  dissolve  at  760  mm.  of  mercury,  that  is,  atmospheric 
pressure. 


S62  RESPIRATION  [CH.  XXVI. 

The  quantity  of  gas  which  a  liquid  will  dissolve  depends  not  only 
on  the  solubility  of  the  gas,  but  upon  the  pressure  of  the  gas  to  which 
the  liquid  is  exposed.  Thus,  in  the  instance  given  above,  if  the 
oxygen  had  been  rarefied  in  the  bottle  until  it  only  exerted  a  pressure 
of  one-fifth  of  an  atmosphere,  the  water  would  have  taken  up  not 
0-04  c.c.  of  oxygen,  but  only  one-fifth  of  that  amount,  0-008  c.c. 
To  take  another  example,  1  c.c.  of  water  shaken  up  with  pure  nitrogen 
at  760  mm.  pressure  will  dissolve  0-02  c.c.  ;  but  suppose  the  pressure 
to  be  reduced  to  four-fifths  of  the  atmospheric  pressure  the  water 
will  dissolve  -02xf  =  -016  c.c.  If  we  represent  the  coefficient  of 
solubility  of  a  gas  by  K,  and  the  pressure  of  the  gas  to  which  the 
liquid  is  exposed  by  P',  and  the  atmospheric  pressure  by  P  ;  then  the 
quantity  (Q)  of  the  gas  dissolved  by  1  c.c.  of  the  liquid  may  be 
obtained  by  the  following  formula  — 


Dalton-Henry  Law. 

What  has  been  said  above  is  as  true  of  gases  which  are  mixed 
together  as  of  pure  gases.  For  instance,  we  have  seen  that  a  cubic 
centimetre  of  water  shaken  up  with  oxygen  at  one-fifth  of  an  atmos- 
phere (153  mm.  pressure)  will  absorb  -04x-J  =-008  c.c.  ;  or  if  shaken 
with  nitrogen  at  a  pressure  of  four-fifths  of  an  atmosphere,  it  will 
dissolve  -02  x  £  =  -016  c.c.  If  now  a  c.c.  of  water  be  shaken  with  air 
(a  mixture  of  one  part  of  oxygen  to  four  of  nitrogen),  it  will  have 
absorbed  -008  c.c.  of  oxygen  and  -016  c.c.  of  nitrogen.  This  fact  has 
been  stated  as  the  Dalton-Henry  Law  in  the  following  words  :  — 
When  two  or  more  gases  are  mixed  together,  each  of  them  produces 
the  same  pressure  as  if  they  separately  occupied  the  entire  space  and 
the  other  gases  were  absent.  The  total  pressure  of  the  mixture  is  the 
sum  of  the  partial  pressures  of  the  individual  gases  in  the  mixture. 

The  Tension  of  Gases  in  Fluids. 

In  the  cases  which  have  been  discussed  up  to  this  point,  a  con- 
dition of  equilibrium  exists  between  the  gas  dissolved  in  the  fluid 
and  the  gas  in  the  atmosphere  to  which  the  fluid  is  exposed,  so  that 
as  m.any  molecules  of  the  gas  leave  the  surface  of  the  fluid  as  enter 
it.  The  gas  dissolved  in  the  fluid  therefore  exercises  a  pressure 
which  is  the  same  as  that  of  the  gas  in  the  atmosphere  when 
equilibrium  exists.  For  the  sake  of  convenience  the  word  Tension 
is  applied  to  the  pressure  of  the  gas  in  the  fluid. 

Definition  of  Tension.  —  The  tension  of  a  gas  dissolved  in  a  fluid 
is  equal  to  the  pressure  of  the  same  gas  in  an  atmosphere  with  which 
the  gas  in  the  fluid  would  be  in  equilibrium.  Above,  we  have  called 


CH.  XXVI.] 


TENSION  OF  GASES 


363 


D— -fe 


the  pressure  which  the  gas  exerts  on  the  liquid,  P'.  If  we  call  the 
tension  of  the  gas  in  the  liquid,  T,  we  find  that  when  equilibrium 
exists,  P'  =  T.  In  the  case  of  all  true  solutions,  therefore,  we  may 

T 

replace   P'  in  our   previous  equation  by  T;   therefore,  Q  =  Kx^p. 

We  thus  arrive  at  a  relation  between  two  separate   things,  which 
must  be  most  carefully  distinguished  from 
one  another — the  quantity  of  the  gas  dis- 
solved in  the  liquid  and  its  tension. 

Measurement  of  Tension.  —  Numerous 
instruments,  called  tonometers,  exist  for 
measuring  the  tension  of  gases  in  fluids. 
Of  these,  the  instrument  which  has  given 
the  most  trustworthy  measurements  of 
the  oxygen  and  carbonic  acid  tensions  in 
circulating  blood  is  that  invented  by  Krogh 
(fig-  292). 

A  T-shaped  cannula  (A)  is  introduced 
into  the  blood-vessel,  say  the  carotid  artery ; 

the  blood  fills  the  cavity  B  and  leaves  it  at    Flo.  292.— Krogh 's  Tonometer. 
C,  so  that  a  constant  stream  of  blood  is  kept 

flowing.  Into  it  a  small  bubble  of  air  (D)  is  introduced.  Exchange 
of  gases  takes  place  between  the  bubble  and  the  blood,  and  the 
former  very  soon  gets  into  equilibrium  with  the  latter.  When  it 
has  done  so,  the  bubble  is  withdrawn  up  the  capillary  tube  E, 
taken  away,  and  analysed. 

As  an  example,  suppose  the  bubble  on  analysis  proved  to  consist 
of  4  per  cent,  carbonic  acid  and  12  per  cent,  oxygen,  together  with 
nitrogen  and  aqueous  vapour.  The  gas  in  the  instrument  was 
compressed  by  the  pressure  of  the  arterial  blood  (say  120  mm.  of 
mercury)  in  addition  to  the  atmospheric  pressure  of  760  mm.  of 
mercury,  and  therefore  the  total  pressure  was  120  +  760  =  880  mm.  of 
mercury.  Four  per  cent,  of  this  would  have  been  due  to  the  carbonic 
acid ;  4  per  cent,  of  880  is  35-2.  Twelve  per  cent,  would  have  been 
due  to  the  oxygen;  12  per  cent,  of  880  is  105-6.  That  is,  the 
carbonic  acid  and  oxygen  tensions  would  have  been  in  round  figures 
35  and  106  mm.  of  mercury  respectively. 

Measurement  of  the  Quantity  of  the  Gases  of  the  Blood. 

This  may  be  done  by  means  of  an  air-pump,  or  by  a  chemical 
method.  (1)  The  extraction  of  the  gases  from  the  blood  by  means 
of  the  mercurial  air-pump  depends  upon  the  fact  that  blood  gives  off 
all  its  gases  when  it  is  boiled  in  a  vacuum.  The  total  gas  obtained 
is  first  measured;  then  the  carbon  dioxide  is  removed  by  caustic 


364 


RESPIRATION 


[CR.  XXVI. 


potash,  and  the  gas  that  remains  consists  of  oxygen  and  nitrogen ; 
the  oxygen  is  then  removed  by  pyrogallic  acid,  and  the  residual  gas 

is  nitrogen.    (2)  The  chemical  method  * 
adopted  is  as  follows : — 

When  a  solution  of  oxyhsemoglobin 
is  shaken  with  potassium  ferricyanide, 
it  yields  the  same  amount  of  oxygen 
to  the  air  as  it  would  if  boiled  in  a 
vacuum.  In  much  the  same  way  urea 
when  treated  with  sodium  hypobromite 
yields  up  all  its  nitrogen,  and  the 
apparatus  used  for  determining  the 
oxygen  in  blood  is  very  similar  to  a 
Dupre's  urea  apparatus  (see  Chapter 
XXXIX.).  The  blood  (5  c.c.)  is  placed 
in  the  large  bottle  (fig.  293,  A)  under- 
neath a  layer  of  dilute  ammonia  solu- 
tion (B).  The  blood  is  thus  protected 
from  the  air  whilst  the  apparatus 
becomes  equal  in  temperature  to  the 
bath  in  which  it  is  placed.  The  blood 
is  shaken  with  the  ammonia  solution, 
which  lakes  it  thoroughly;  the  ferri- 
cyanide solution  is  then  spilt  into  the 
laked  blood  from  the  tube  C,  and  the 
oxygen  is  shaken  out  of  the  solution. 
When  the  oxygen  has  been  determined 
the  bottle  is  opened  and  tartaric  acid 
is  placed  in  the  small  tube  C ;  this  is 
subsequently  spilt  into  the  mixture  of 
blood,  ammonia,  and  ferricyanide;  it 
liberates  the  carbonic  acid  which  is  also 
shaken  out  of  the  fluid.  The  carbonic 
acid  does  not  come  completely  out, 
however,  and  a  correction  has  to  be 
introduced  for  the  quantity  which 
remains  in  solution.  The  gas  (oxygen 
or  carbonic  acid,  as  the  case  may  be)  passes  over  into  the  tube 
D,  which  was  previously  filled  up  to  the  zero  mark  with  water, 
and  connected  to  a  reservoir  (F) ;  this  would  drive  water  out  of  F 

*  The  apparatus  figured  is  one  of  the  earliest,  and  many  modifications  have 
been  invented  since  which  are  in  use  in  different  laboratories.  The  differences  are, 
however,  in  detail  only ;  the  principle  throughout  is  the  same.  The  details  of  the 
mercury  pump  I  have  considered  it  best  to  omit.  They  are  very  complicated,  and 
the  forms  of  pump  used  vary  greatly  in  different  laboratories ;  the  method  can  only 
be  learnt  by  actually  using  the  instrument. 


FIG.  293.— Apparatus  for  blood-gas 
analysis. 


CH.  XXVI.]   MEASQHEMENT  OF  THE  QUANTITY  OF  THE  GASES      365 

into  the  open  tube  E,  and  the  water  will  therefore  rise  in  E ;  but  in 
practice  it  is  convenient  to  keep  the  gas  always  at  the  same  volume ; 
this  may  be  done  by  raising  the  pressure  in  the  open  limb  (E)  of  the 
pressure  gauge  by  squeezing  some  of  the  water,  with  which  the 
gauge  is  filled,  out  of  a  rubber  reservoir  (G)  which  forms  the  base  of 
the  gauge,  thus  the  level  of  the  water  in  D  is  maintained  at  the  zero 
mark,  while  that  in  E  rises  from  H  to  I.  The  actual  measurement 
then  is  the  increase  of  pressure  (i.e.,  the  height  of  the  column  of 
water  H  I)  which  is  necessary  to  keep  the  gas  at  the  same  volume 
after  the  oxygen  or  carbonic  acid  has  been  shaken  off  as  it  previously 
occupied.  From  this  the  quantity  coming  off  can  be  calculated. 

The  chemical  method  is  not  quite  so  accurate  as  the  vacuum 
pump,  but  it  is  much  more  convenient  for  the  study  of  many 
problems,  as  it  requires  less  blood,  and,  owing  to  its  simplicity, 
a  great  number  of  observations  can  be  made  upon  a  single  animal,  or 

it  can  be  used  for  the  systematic  investigation  of  the  blood  in  man. 
/ 

Relation  between  Quantity  and  Tension  of  Gases  in  Blood. 

In  the  preceding  paragraphs  the  methods  of  measuring  the  tension 
and  the  quantity  of  gas  in  a  given  sample  of  blood  have  been  described. 
It  is  now  necessary  to  consider  the  relationship  between  them. 

On  page  363  we  have  seen  that  for  gases  in  solution  in  water, 

T 

Q  =  K  x  -p-  where  Q  is  the  quantity  of  gas  dissolved,  T  the  tension, 

K  the  coefficient  of  solubility,  and  P  the  atmospheric  pressure. 
Since  K  and  P  are  constant,  it  follows  that  Q  varies  directly  in 
proportion  to  T ;  that  is  to  say,  if  the  tension  is  doubled,  the  quan- 
tity of  gas  dissolved  is  also  doubled ;  if  the  tension  is  trebled,  the 
quantity  of  gas  is  trebled,  and  so  on.  These  results  might  be 
plotted  out  on  a  curve  in  which  the  quantities  are  placed  on  the 
ordinate  and  the  tension  on  the  abscissa.  Such  a  curve  would  give 
the  quantity  of  gas  dissolved  at  any  given  tension,  and  in  the  case 
of  water  the  curve  would  turn  out  to  be  a  straight  line. 

But  in  the  case  of  both  the  oxygen  and  the  carbonic  acid  in 
blood,  the  curve  is  not  a  straight  line. 

Oxygen  in  Blood. — From  every  100  c.c.  of  arterial  blood,  about 
20  c.c.  of  oxygen  can  be  removed  by  the  air-pump.  Nearly  all  of  this 
oxygen  is  chemically  combined  with  haemoglobin ;  the  amount  in 
actual  solution  in  the  blood  is  0-7  c.c.  for  every  100  c.c.  of  blood. 
The  quantity  of  oxygen  which  100  c.c.  of  blood  takes  up  is  called  the 
"oxygen  capacity"  which  should  not  be  confounded  with  the 
"specific  oxygen  capacity"  defined  below.  In  normal  human 
blood,  the  figure  is  18*5  c.c.,  and  this  forms  the  basis  of  standardisa- 
tion of  haemoglobinoineters  (p.  445). 


366 


RESPIRATION 


[CH.  XXVI. 


Haemoglobin  owes  its  value  as  a  respiratory  pigment  to  two 
principal  facts.  (1)  It  can  unite  with  a  large  quantity  of  oxygen, 
and  therefore  blood  can  carry  about  thirty  times  as  much  oxygen  to 
the  tissues  as  plasma  would  under  the  same  circumstances.  (2)  The 
interaction  between  haemoglobin  and  oxygen  is  a  reversible  one ; 
the  two  unite  in  the  lungs,  where  the  pressure  of  oxygen  is  high; 
but  when  oxygen  is  absent  or  at  a  low  pressure,  as  in  the  tissues,  the 
haemoglobin  parts  with  its  store  of  oxygen. 

The  reaction  between  haemoglobin  and  oxygen  is  a  chemical  one. 
At  most,  one  gramme  of  haemoglobin  can  unite  with  1/34  c.c.  of 
oxygen.  This  figure  is  not  quite  constant,  probably  on  account  of 
slightly  different  forms  of  globin  (the  protein  constituent  of  haemo- 
globin) united  with  the  haematin  (the  iron  containing  constituent) 
in  different  animals.  The  relation  between  the  respiratory  oxygen 
and  the  iron  of  the  haemoglobin  is,  however,  quite  constant,  and  is 
called  the  "specific  oxygen  capacity"  Each  gramme  of  iron  in 
haemoglobin  unites  with  400  c.c.  of  oxygen ;  these  figures  are  in  the 
relation  of  one  atom  of  iron  to  two  atoms  of  oxygen.  The  reversible 
nature  of  the  reaction  may  therefore  be  expressed  by  the  equation 
H6  +  02  ^^  H&02.  A  reversible  reaction  means  that  it  will  go  in 
either  direction  according  to  the  concentration  of  the  substances 
present ;  thus  if  the  concentration  of  oxygen  in  solution  is  increased, 


\ 


FIG.  294.—  Barcroft's  Tonometer,  suspended  horizontally  in  warm  bath  in  which  it  is  rotated. 

more  of  the  haemoglobin  will  become  oxyhaemoglobin ;  and  if  it 
is  diminished,  oxyhaemoglobin  will  break  up  into  haemoglobin  (some- 
times called  reduced  haemoglobin)  and  oxygen. 

The  reader  must  be  clear  that  when  we  speak  of  the  concentration 
of  oxygen  in  solution,  we  mean  in  physical  solution,  that  is,  not 
united  chemically  with  the  haemoglobin.  This  quantity  varies  in 
the  direct  ratio  of  the  oxygen  pressure  to  which  the  haemoglobin 
solution  is  exposed ;  therefore  the  problem  before  us  is  to  determine 
the  relative  quantities  of  oxy-  and  reduced  haemoglobin  when  a 
haemoglobin  solution  is  shaken  up  with  oxygen  at  different  pressures. 


CH.  XXVI.]        RELATION   BETWEEN   QUANTITY  AND   TENSION 


367 


Suppose  that  we  have  six  vessels  similar  to  that  in  fig.  294 
(Bancroft's  Tonometer),  and  each  contains  a  few  c.c.  of  a  solution  of 
haemoglobin  and  gases  of  the  following  composition : — 

No.  1.  Nitrogen  and  no  oxygen. 

No.  2.  Nitrogen  and  enough  oxygen  to  give  5  mm.  oxygen  pressure. 

No.  3.  ,,  ,,  10  „   '  „ 

No.  4.  „  „  „  20 

No.  5.          „  „  „  50 

No.  6.  ,,  „  ,,  100 

Each  tonometer  is  rotated   round   and   round   in   a   bath  at  body 
temperature  until  the  haemoglobin  and   the  oxygen  are  in  equili- 

TQtal  Haemoglobin  100 
'  Percentage   Percentage^ 
of  reduced    ofOxyhaemo 
haemoglobin,     globm 

0  ' 
6 
13 


45 


63 


100 


0    5    10        20  50 

Oxygen  Pressure  in  mm.  of  Mercury. 


FIG,  295. — Dissociation  curve  of  haemoglobin    solution   at  37°  C.      Purple,   reduced    hemoglobin  ; 

red,  oxyhiiemoglobin. 

brium;  this  will  take  about  a  quarter  of  an  hour;  the  solution 
is  then  withdrawn  and  examined  in  order  to  ascertain  the  relative 
quantities  of  oxy-  and  reduced  haemoglobin  in  the  six  vessels. 


368  RESPIRATION  [CH.  XXVI. 

The  figures  for  a  pure  solution  of  haemoglobin  would  be  :— 

No.  1.     No.  2.     No.  3.     No.  4.     No.  5.     No.  6. 

Percentage  of  haemoglobin         .         100         63         45         28         13  6 

Percentage  of  oxyhaemoglobin   .  0        37        55        72        87        94 


100       100       100       100       100       100 

The  same  answer  may  be  expressed  graphically ;  if  the  pressures 
of  oxygen  are  plotted  horizontally,  and  the  percentages  of  oxy- 
and  reduced  hsemoglobin  in  the  solution  are  plotted  vertically,  we 
get  the  curve  shown  in  the  accompanying  diagram  (fig.  295),  which  is 
called  the  dissociation  curve  of  licemoglobin. 

In  a  reversible  reaction  such  as  the  one  under  consideration,  the 
molecules  are  continually  forming  and  breaking  up  again,  and  the 
rate  at  which  this  occurs  is  influenced  by  various  conditions. 
Among  the  conditions  of  importance  in  the  body  are  (1)  tempera- 
ture; (2)  the  presence  of  salts;  and  (3)  the  presence  of  acids, 
especially  carbonic  acid.  These  factors  tend  to  make  the  oxyhaemo- 
globin molecules  break  down  more  rapidly  and  form  more  rapidly. 
From  the  point  of  view  of  the  body's  needs,  it  is  clearly  necessary, 
not  only  that  hsemoglobin  should  acquire  oxygen  at  the  pressure  of 
that  gas  in  the  lungs,  and  part  with  it  at  the  diminished  oxygen 
pressure  in  the  tissues,  but  that  the  two  processes  should  occur  at 
about  the  same  rate,  that  is,  within  one  second,  which  is  about  the 
time  occupied  by  any  given  portion  of  blood  in  travelling  along  the 
capillaries  (see  p.  282). 

It  would  be  futile  to  have  an  oxygen  carrier  in  the  blood  which 
took  a  fraction  of  a  second  to  acquire  its  oxygen,  and  a  fraction  of 
an  hour  to  release  it.  Yet  a  solution  of  pure  haemoglobin  is  just 
such  a  substance,  for  its  power  of  acquiring  oxygen  is  very  great, 
and  its  power  of  releasing  it  is  very  small.  Happily,  however,  a 
haemoglobin  solution  and  blood  are  two  very  different  things.  In 
the  red  corpuscles,  the  haemoglobin  is  dissolved  in  a  medium  con- 
taining various  salts  of  which  those  of  potassium  are  most  prominent ; 
these  salts  confer  on  haemoglobin  the  property  of  giving  up  its 
oxygen  much  more  readily  when  exposed  to  low  concentrations  of 
oxygen  such  as  are  present  in  the  capillaries  of  the  tissues,  while  at 
the  same  time  it  acquires  oxygen  more  readily  at  higher  oxygen 
pressures  such  as  blood  is  exposed  to  in  the  lungs.  But  the  mere 
presence  of  potassium  salts  is  not  in  itself  capable  of  rendering  the 
haemoglobin  an  efficient  oxygen  carrier ;  two  other  factors  come  into 
play  in  the  body — one  is  the  high  temperature,  and  the  second  is  the 
presence  of  carbonic  acid.  This  is  illustrated  in  the  curves  depicted  in 
fig.  296.  —To  obtain  the  rate  of  oxidation,  oxygen  at  alveolar  pressure, 
mixed  with  nitrogen,  was  passed  through  reduced  blood  ;  to  obtain  the 
rate  of  reduction,  nitrogen,  free  from  oxygen,  was  passed  through 


CH.  XXVI.]        KELATION  BETWEEN   QUANTITY  AND   TENSION 


369 


oxygenated  blood.  The  vertical  figures  represent  the  percentage 
saturation  of  blood  with  oxygen ;  the  horizontal  figures  represent 
time  in  minutes. 

It  will  be  seen  that  at  room  temperature  (A),  the  rate  of  oxidation 
is  rapid,  but  the  rate  of  reduction  is  very  slow.  At  body  temperature 
the  rate  of  reduction  is  enormously  increased  (B);  but  at  body 
temperature  in  the  presence  of  carbonic  acid  the  two  rates  are 
practically  equal  (C) ;  the  amount  of  carbonic  acid  employed  was  the 
same  as  that  which  pervades  the  body,  viz.,  at  a  tension  of  40  mm.  of 
mercury.  This  quantity  is  also  approximately  equal  to  that  present 


100 


A 


0       6       10      15      2O     25    3O 
minutes. 

17°  c  Free  from  CO 2 


OS       iO      t5       2O      25     3O 
misuses 

37  °c  Free  from  C02 


O       6       JO       /5      20      25      3O 
minutes. 

37  °c  40mm.  C02 


FIG.  296. — Curves  showing  rate  of  oxidation  and  reduction  in  blood  under  the  conditions  described  in 
the  text;  A,  at  room  temperature  (17°  C.) ;  B,  at  body  temperature  (37°  C.);  C,  at  body  tempera- 
ture when  carbon  dioxide  at  40  mm.  pressure  was  added  to  the  nitrogen. 


in  the  alveolar  air.  The  curves  show  that  the  rate  of  reduction  is  in- 
creased, but  the  rate  of  oxidation  is  a  little  lessened.  The  two  curves 
in  C  present  an  extraordinary  degree  of  symmetry,  so  wonderfully  has 
nature  adapted  the  conditions  of  life  in  order  that  the  needs  of  the 
body  may  be  served  by  a  substance  haemoglobin  which  by  itself  is 
ill  adapted  for  the  purpose  of  oxygen  transport. 

In  order  therefore  to  understand  the  dissociation  of  oxygen  from 
haemoglobin  in  the  body,  we  must  study  it,  not  in  a  pure  solution, 
but  under  the  more  complex  conditions  actually  existing  in  the  body, 

2  A 


370  RESPIRATION  [CH.  XXVI. 

Under  these  conditions,  viz.,  in  the  presence  of  potassium  salts,  at 
37°  C.,  and  in  the  presence  of  a  carbonic  acid  pressure  of  40  mm.  Hg, 
the  dissociation  curve  is  that  shown  in  the  next  diagram  (fig.  279). 

The  two  coloured  figures  (295  and  297)  should  be  carefully 
compared;  they  present  to  the  eye  graphically  the  superiority  of 
hsemoglobin  as  an  oxygen  carrier  when  it  is  present  in  the  actual 
blood,°over  that  which  it  possesses  in  a  pure  solution.  In  the  second 


.,  —  • 

„  — 

—  —  — 

IUU 

90  5 

CT 

80^ 

^r 

70  s 

•a 
60  8 

GO 

50  1 

C 

o 
40  to 

c_ 

30  S 

0) 

20^ 
"c 

10  ^ 

a 

/ 

^ 

/ 

/ 

. 

/ 

/ 

/ 

I 

/ 

^y 

10        20        30        40        50       60        70       80        90       100 

Oxygen  Pressure  in  mm.  of  Mercury 

FIG.  297.— Dissociation  curve  of  hsemoglobin  in  the  actual  blood.     Purple,  reduced 
haemoglobin ;  red,  oxyhsemoglobin. 


curve,  that  of  the  blood  itself,  it  will  be  seen  that  at  an  oxygen 
pressure  of  over  60  mm.  of  mercury  (the  pressure  in  the  lung  alveoli 
is  about  100)  the  blood  will  nearly  saturate  itself  with  oxygen,  and 
that  at  pressures  below  50  the  blood  loses  its  oxygen  rapidly,  whilst 
at  10  mm.  pressure  it  is  nearly  completely  reduced.  As  the  rate  at 
wh'ich  oxygen  can  diffuse  out  of  the  capillaries  into  the  surrounding 
tissues  depends  upon  the  pressure  it  exerts  in  the  plasma,  it  is 
important  that  the  haemoglobin  of  the  blood  should  be  capable  of  a 


CH.  XXVI.]  GASES   OP  ARTERIAL  AND   VENOUS   BLOOD  371 

considerable  degree  of  reduction  when  it  is  in  contact  with  fluid 
containing  oxygen  at  a  pressure  of  20  to  30  mm.  of  mercury. 

Carbonic  Acid  in  Blood. — If  blood  is  divided  into  plasma  and 
corpuscles,  it  will  be  found  that  both  yield  carbonic  acid,  but  the 
yield  from  the  plasma  is  the  greater.  If  we  place  blood  in  a  vacuum 
it  bubbles,  and  gives  out  all  its  gases;  addition  of  a  weak  acid 
causes  no  further  liberation  of  carbonic  acid.  When  plasma  or 
serum  is  similarly  treated  the  gas  also  comes  off,  but  about  5  per 
cent,  of  the  carbonic  acid  is  fixed — that  is,  it  requires  the  addition  of 
some  stronger  acid,  such  as  phosphoric  or  tartaric  acid,  to  displace  it. 

One  hundred  volumes  of  venous  blood  contain  about  forty-six 
volumes  of  carbonic  acid.  Whether  this  is  in  solution  or  in  chemical 
combination  is  determined  by  ascertaining  the  tension  of  the  gas  in  the 
blood.  One  hundred  volumes  of  blood  plasma  would  dissolve  about 
an  equal  volume  of  the  gas  from  an  atmosphere  of  carbonic  acid,  if  its 
solubility  in  plasma  were  equal  to  that  in  water.  If,  then,  the  carbonic 
acid  were  in  a  state  of  solution,  its  tension  would  be  very  high,  but,  as 
we  have  seen,  it  proves  to  be  only  equal  to  about  5  per  cent,  of  an 
atmosphere  (that  is  approximately  equal  to  40  mm.  of  mercury). 
This  means  that  when  venous  blood  is  brought  into  an  atmosphere 
containing  5  per  cent,  of  carbonic  acid,  the  blood  neither  gives  off 
any  carbonic  acid  nor  takes  up  any  from  that  atmosphere.  Hence 
the  remainder  of  the  gas,  41  per  cent.,  is  in  a  condition  of  chemical 
combination. 

Of  the  carbonic  acid  present  in  chemical  composition,  the  greater 
part  is  present  as  sodium  bicarbonate  (NaHC03).  About  a  third  is 
in  loose  combination  with  the  proteins  of  the  blood,  and  a  small 
quantity  exists  as  normal  sodium  carbonate  (Na2C03). 

Differences  bet-ween  Arterial  and  Venous  Blood. — The  aver- 
age quantity  of  gas  that  can  be  extracted  from  arterial  and  venous 
blood  respectively  is  : — 

Arterial  blood.  Venous  blood. 

Oxygen 20  8  to  12 

Nitrogen         ....                 1  to  2  1  to  2 

Carbonic  acid         ...                   40  46  to  50 

It  will  be  noticed  that  the  amount  of  nitrogen  which  is  simply 
dissolved  in  the  blood  from  the  air  is  small  in  amount.  It  has  no 
physiological  significance,  and  is  the  same  in  both  varieties  of  blood. 
The  important  distinction  between  arterial  and  venous  blood  is  in 
the  other  two  gases,  and  as  the  table  shows,  on  the  average  every 
100  c.c.  of  blood  which  pass  through  the  lungs  gain  8  c.c.  of  oxygen 
and  lose  6  c.c.  of  carbonic  acid.  We  will  now  study  the  mechanism 
by  which  this  gaseous  interchange  is  effected. 


372  RESPIRATION  [CH.  XXVI. 

The  Mechanism  of  Gaseous  Exchange  in  the  Lung. 

1.  Oxygen. 

The  simplest  explanation  of  the  passage  of  oxygen  from  the  alveolar 
air  into  the  blood  is  that  the  process  is  one  of  diffusion.  This  view 
(which  is  generally  regarded  as  adequate  in  the  case  of  normal 
respiration)  can  be  maintained  if  it  can  be  proved  that  the  pressure 
of  oxygen  in  the  alveolar  air  is  as  great  or  greater  than  the  tension 
of  oxygen  in  the  arterial  blood,  and  therefore  a  fortiori  greater  than 
that  of  oxygen  in  the  venous  blood. 

The  conception  of  respiration  based  upon  this  view  would  be  that 
the  pressure  of  oxygen  in  the  air  of  the  alveoli  though  less  than  that 
in  the  atmosphere,  is  greater  than  that  in  venous  blood ;  hence  oxygen 
passes  from  the  alveolar  air  into  the  blood  plasma;  the  oxygen 
immediately  combines  with  the  haemoglobin,  and  thus  leaves  the 
plasma  free  to  absorb  more  oxygen;  and  this  goes  on  until  the 
haemoglobin  is  entirely,  or  almost  entirely,  saturated  with  oxygen. 
The  reverse  change  occurs  in  the  tissues  when  the  partial  pressure 
of  oxygen  is  lower  than  in  the  plasma,  or  in  the  lymph  that  bathes 
the  tissue  elements ;  the  plasma  parts  with  its  oxygen  to  the  lymph, 
the  lymph  to  the  tissues;  the  oxyhaemoglobin  then  undergoes  dis- 
ifeciation  to  supply  more  oxygen  to  the  plasma  and  lymph,  and  thus 
in  turn  to  the  tissues  once  more.  This  goes  on  until  the  oxyhaemo- 
globin loses  on  the  average  about  half  of  its  store  of  oxygen;  1 
c.c.  of  arterial  blood  contains  0-2  c.c.  oxygen;  1  c.c.  of  venous 
blood  contains  0-1  c.c.  oxygen. 

Haldane  and  Priestley  introduced  a  very  simple  method  of 
collecting  alveolar  air  which  has  the  advantage  of  being  applicable  to 
man.  A  piece  of  rubber  tubing  is  taken  about  1  inch  in  diameter 
and  about  4  feet  long.  A  mouthpiece  is  fitted  into  one  end.  About 
2  inches  from  the  mouthpiece  a  small  hole  is  made  into  which  is 
inserted  the  tube  of  a  gas-receiver,  or  sampling-tube,  as  in  the 
figure  (fig.  298).  The  gas-receiver  is  fitted  at  the  upper  end  with 
a  three-way  tap,  and  the  lower  end  is  also  closed  by  a  tap.  Before 
it  is  used,  it  is  filled  with  mercury.  The  subject  of  the  experi- 
ment breathes  normally  through  the  tube  for  a  time,  and  then, 
at  the  end  of  a  normal  inspiration,  he  expires  quickly  and  very 
deeply  through  the  mouthpiece  and  instantly  closes  it  with  his 
tongue.  The  lower  tap  of  the  receiver  is  then  turned,  and  as 
the  mercury  runs  out,  a  sample  of  the  air  takes  its  place  and 
fills  the  receiver;  this  sample  is  then  analysed.  A  second  experi- 
ment is  then  done,  in  which  the  subject  expires  deeply  at  the  end 
of  a  normal  expiration,  and  another  sample  obtained.  The  mean 


CH.  XXVI.]          COLLECTION  OF  ALVEOLAR  AIR  373 

result  of  the  two  analyses  represents  the  mean  composition  of  the 
alveolar  air.  Since  the  gaseous  interchange  between  the  blood  and 
the  alveolar  air  is  going  on  continuously,  it  is  evident  that  at  the 
end  of  inspiration  there  will  be  a  maximum  percentage  of  oxygen, 
and  a  minimum  percentage  of  carbonic  acid ;  the  converse  obtains 
at  the  end  of  expiration.  These  observers  proved  by  other  consitfera- 
tions  which  it  is  unnecessary  to  go  into,  that  the  air  obtained  was 
really  the  alveolar  or  residual  air  unmixed  with  any  of  the  air  of  the 
"  dead  space  "  of  the  respiratory  passages. 

From  the  analysis  of  this  air,  they  arrived  at  the  conclusion  that 
the  normal  oxygen  pressure  in  it  is  13  per  cent,  of  an  atmosphere 
(that  is  approximately  equal  to  100  mm.  of  mercury). 

The  other  important  measurement,  namely  that  of  the  tension  of 
oxygen  in  the  blood,  is  made  by  Krogh's  tonometer  (p.  363),  and  the 
experiments  show  that  diffusion  is  quite  sufficient  to  account 


MOUTHPIECE 


SAMPLING  TUBE 


FIG.  298.— Apparatus  for  obtaining  alveolar  air. 

for  the  passage  of  oxygen  from  the  alveoli  to  the  blood.  The 
following  experiment  may  be  cited  as  an  example,  and  will  be  best 
understood  by  the  next  diagram  (fig.  299). 

It  shows  the  relations  between  the  pressures  of  oxygen  and 
carbonic  acid  in  the  air  of  the  lungs  and  the  blood  respectively. 
The  pressures  of  gas  are  measured  vertically,  and  expressed  as 
percentages  of  an  atmosphere;  the  horizontal  measurements  are 
those  of  time.  It  will  be  seen  that  the  experiment  consisted  of 
three  periods,  separated  by  the  vertical  lines  A  and  B.  During  the 
first  and  last  periods  the  animal  breathed  a  mixture  consisting  of 
14-7  per  cent,  oxygen,  and  the  remainder  nitrogen;  in  the  middle 
period  ordinary  air  containing  nearly  21  per  cent,  of  oxygen  was 
breathed.  It  will  be  seen  that  the  oxygen  pressure  of  the  alveolar 
air  (dotted  line)  is  always  higher  than  the  oxygen  tension  of  the 
arterial  blood  (continuous  black  line) ;  as  the  former  rises  the  latter 
rises,  and  vice  versa.  The  lower  part  of  the  diagram  shows  the 


374 


RESPIRATION 


[CH.  XXVI. 


relationships  of  the  carbon  dioxide;  the  alveolar  tension  of  this  gas 
(dotted  line)  is  always  lower  than  that  of  the  arterial  blood  (continu- 
ous black  line).  It  will  further  be  noticed  that  the  pressure 
differences  are  less  in  the  case  of  carbonic  acid  than  in  that  of 
oxygen  ;  this  coincides  with  the  ease  with  which  carbonic  acid  passes 
out  through  the  membrane  which  separates  the  blood  from  the  air. 


10      20      30      40      50      60      70      80      90  minutes. 


FIG.  299. — Diagram  to  represent  the  relationship  between  the  tensions  of  oxygen  and  carbon  dioxide 
in  blood  and  alveolar  air  in  rabbit  (after  Krogh). 

Some  authorities  consider  that  in  cases  of  definite  oxygen  want, 
such  as  during  violent  muscular  exercise,  or  on  the  tops  of  high 
mountains,  the  lining  epithelium  of  the  pulmonary  alveoli  can,  by  a 
process  of  active  secretion,  transfer  oxygen  from  the  alveolar  air  to 
the  blood.  In  the  case  of  exercise  the  observations  made  by  different 
workers  are  at  variance,  whilst  at  high  altitudes  they  are  so  few  as 
to  make  further  work  desirable  before  physiologists  generally  can 
accept  the  possibility  of  the  secretion  of  oxygen  by  the  lung.  That 


CH.  XXVI.]  CARBONIC    ACID   IN   THE   BLOOD  375 

secretion  is  not  impossible  is  shown  by  the  fact  that  a  similar 
secretion  of  oxygen  is  known  to  occur  in  the  swim-bladder  of  certain 
fishes.  The  swim-bladder  corresponds  morphologically  with  the  lungs 
of-  a  mammal,  and  the  oxygen  stored  in  it  is  far  in  excess  of  anything 
that  can  be  explained  by  mere  diffusion  from  the  sea-water.  This 
storage  of  oxygen,  moreover,  ceases  when  the  vagus  nerves  which 
supply  the  swim-bladder  are  divided. 

2.  Carbonic  Acid. 

The  tension  of  carbonic  acid  in  the  alveolar  air  is  measured,  like 
that  of  oxygen,  by  the  method  of  Haldane  and  Priestley,  whilst  the 
tension  in  the  blood  is  measured  by  the  tonometer. 

The  tension  of  the  carbonic  acid  in  the  tissues  is  high,  but  one 
cannot  give  exact  figures ;  we  can  measure  the  tension  of  the  gas  in 
certain  secretions :  in  the  urine  it  is  9,  in  the  bile  7  per  cent.  The 
tension  in  the  cells  themselves  must  be  higher  still. 

The  following  figures  (from  Fredericq)  give  the  tension  of  carbonic 
dioxide  in  percentages  of  an  atmosphere : — 

Tissues 5  to  9     \                  ^ 

Venous  blood   .         .         .         .         .         .         .  3*8  to  5*4  J-  in  dog. 

Alveolar  air 2'8       ) 

External  air 0'04 

The  arrow  indicates  the  direction  in  which  the  gas  passes,  namely, 
in  the  direction  of  pressure  from  the  tissues  to  the  atmosphere. 

In  view  of  the  above  figures  and  of  such  experiments  as  that  of 
Krogh,  cited  on  the  opposite  page,  and  having  regard  to  the  very  slight 
changes  in  the  tension  of  carbonic  acid  in  the  alveolar  air,  which  are 
capable  of  affecting  the  respiratory  centre  (a  subject  we  shall 
immediately  pass  to),  we  shall  adhere  to  the  view  that  diffusion 
explains  the  passage  of  that  gas  from  the  blood  to  the  alveolar 
air,  and  that  it  is  unnecessary  to  call  to  our  assistance  the  hypothesis 
that  secretory  activity  of  the  alveolar  epithelium  is  at  work. 

Cause  and  Regulation  of  Respiration. 

There  are  three  factors,  each  of  which  plays  a  part  in  maintaining 
and  regulating  the  rhythmic  movements  of  respiration.  They  are 
the  respiratory  centre,  the  vagus  nerves,  and  the  chemical  condition 
of  the  blood. 

1.   The  Respiratory  Centre. 

In  the  central  nervous  system  there  is  a  specialised  small  district 
called  the  respiratory  centre.  This  gives  out  impulses  which  travel 
down  the  spinal  cord  to  the  centres  of  the  spinal  nerves  that 
innervate  the  muscles  of  respiration.  It  also  receives  various  afferent 
fibres,  the  most  important  of  which  are  contained  in  the  trunk  of  the 


376  RESPIRATION  [CH.  XXVI. 

vagus.  The  vagus  is  chiefly  an  afferent  nerve  in  relation  to  respira- 
tion. It,  however,  also  is  in  a  minor  degree  efferent,  for  it  supplies 
the  muscular  tissue  of  the  lungs  and  bronchial  tubes,  and  exercises  a 
trophic  influence  on  the  lung. 

The  respiratory  centre  was  discovered  by  Flourens ;  it  is  situated 
at  the  tip  of  the  calamus  scriptorius,  and  coincides  in  position 
with  the  sensory  centre  of  the  vagus.  The  existence  of  subsidiary 
respiratory  centres  in  the  spinal  cord  has  been  mooted,  but  the 
balance  of  experimental  evidence  is  against  their  existence.  Flourens 
found  that  when  the  respiratory  centre  is  destroyed,  respiration  at 
once  ceases,  and  the  animal  dies.  He  therefore  called  it  the  "  vital 
knot "  (noeud  vitale). 

The  centre  is  affected  not  only  by  the  afferent  impulses  which 
reach  it  by  such  nerves  as  the  vagus,  but  also  by  those  from  the 
cerebrum;  so  that  we  have  a  limited  amount  of  voluntary  control 
over  the  respiratory  movements. 

The  respiratory  centre  is  probably  twofold,  consisting  of  an 
inspiratory  and  an  expiratory  centre.  Of  these  two  the  inspiratory 
centre  is  so  much  the  more  active  that  its  importance1  is  a  subject  of 
universal  agreement ;  whereas,  the  existence  of  an  expiratory  centre 
is  doubted  by  some  physiologists,  who  regard  expiration  as  a  mere 
cessation  of  the  active  process  of  inspiration,  and  a  mechanical  falling 
back  of  the  tissues  into  their  places. 

2.  The  Nervous  Factor  in  Respiration. 

During  normal  respiration,  as  opposed  to  forced  respiration,  an 
impulse  passes  from  the  lung  to  the  respiratory  centre  during  each 
complete  respiration.  This  has  been  discovered  by  placing  the 
vagus  on  non-polarisable  electrodes  connected  to  a  galvanometer, 
and  observing  the  current  of  action  which  accompanies  each  impulse. 
The  action-current  takes  place  at  the  height  of  each  inspiration. 

The  currents  that  occur  in  the  vagus  during  respiration  can  be 
investigated  with  the  capillary  electrometer,  as  was  done  by  Alcock 
and  Seemann ;  they  can  still  be  more  accurately  studied  by  the  use  of 
Einthoven's  string  galvanometer  (see  p.  121).  The  accompanying 
figures  (fig.  300)  are  reproduced  from  Einthoven's  work  on  the  sub- 
ject. They  were  obtained  from  a  dog. 

In  fig.  300  A,  normal  respiration  was  taking  place,  and  the  line  E 
is  a  tracing  of  the  respiratory  movements ;  the  lowermost  line  (H)  is 
a  tracing  of  the  heart-beats.  The  top  tracing  (E)  is  a  photographic 
record  of  the  movement  of  the  quartz  fibre  in  the  galvanometer,- 
which  was  connected  by  electrodes  to  the  vagus  nerve.  The  vago- 
electrogram,  as  we  may  term  it,  shows  large  waves,  which  indicate  the 
changes  in  the  activity  of  the  nerve  in  reference  to  respiration ;  the 


CH.  XXVI.] 


NERVOUS   FACTOR   IN   RESPIRATION 


377 


smaller  waves  upon  these  are  due  to  its  activity  in  reference  to  the 
heart.* 

In  fig.  300  B,  a  condition  of  apncea  was  produced  so  that  the  dog 
did  not  breathe  for  a  certain  time.  The  vagogram  therefore  shows 
no  respiratory  waves;  and  the  variations  due  to  cardiac  action  are 
the  only  waves  seen. 

During  normal  respiration,  then,  it  seems  that  the  inspiratory 
centre  alone  is  active,  and  that  after  the  inspiration  has  reached  a 


B 

Fio.  300.— A,  Upper  line  (E)  is  the  electro-vagogram ;  the  middle  tracing  K  is  that  of  the  respiratory 
movements;  the  lowermost  line  (H)  is  a  tracing  of  the  heart-beats.  In  B,  apnoea  was  produced, 
and  the  electro-vagogram  shows  only  the  electrical  variations  in  the  vagus,  which  are  due  to 
cardiac  action.  (Einthoven.) 

certain  point,  it  is  checked  by  an  impulse  (inhibitory)  coming  from 
the  lung  along  the  vagus, 

A  theoretical  question  arises  at  this  point:  Supposing  no 
inhibitory  impulse  came  up  the  vagus,  would  the  inspiration  ever 
cease  of  itself  ?  In  answer  to  this  question  we  may  say  at  once  that 
when  both  vagi  are  divided,  the  respirations  become  much  slower 
and  deeper,  but  they  do  not  entirely  cease.  If  this  were  the  whole 
case,  we  should  conclude  that  the  respiratory  centre  had  a  slow 

*  Einthoven  regards   these  as  mainly  due  to  afferent  (depressor)  impulses  ; 
whether  this  is  so  or  not  is  immaterial  to  the  main  question  discussed  above. 


378  RESPIRATION  [CH.  XXVI. 

inherent  rhythm,  which  was  quickened  by  the  vagus  impulses ;  but 
it  is  claimed  that  when  all  impulses,  both  from  the  brain  above  and 
the  sensory  nerves  below,  are  cut  off  from  the  respiratory  centre, 
the  respiratory  rhythm  ceases.  The  operation  is,  however,  a  very 
severe  one,  and  therefore  inconclusive. 

Leaving  the  question  of  normal  respiration,  we  may  proceed  to 
consider  the  impulses  passing  up  the  vagus  during  forced  respiration. 
The  presence  of  impulses  in  these  nerves  can  again  be  best  detected 
by  their  action-currents,  and  in  forced  inspiration  the  same  action- 
current  is  shown  by  the  galvanometer  as  we  have  just  mentioned 
occurs  during  normal  breathing;  it  can  also  be  induced  by  artificial 
inflation  of  the  lung.  When  the  lung  is  alternately  and  deeply 
inflated  and  deflated,  a  small  electrical  variation  frequently  appears 
also  in  the  vagus  nerve  during  each  deflation.  We  have,  therefore, 
evidence  that  a  nervous  impulse  is  passing  up  the  vagus  during  this 
period,  but  whether  this  impulse  of  the  expiratory  period  is  inhibitory 
to  an  expiratory  centre,  or  a  stimulus  to  an  inspiratory  centre,  is  very 
difficult  to  decide.  The  following  experiments  of  Head,  however, 
suggest  the  existence  of  a  double  centre. 

His  method  of  recording  the  movements  was  by  means  of  that  con- 
venient slip  of  the  diaphragm  which  is  found  in  rabbits  (see  p.  357). 

His  method  of  dividing  the  vagus  was  by  freezing  it ;  he  laid  it 
across  a  copper  wire,  the  end  of  which  was  placed  in  a  freezing 
mixture.  This  method  is  free  from  the  disadvantage  which  a  cut 
with  a  knife  or  scissors  possesses,  namely,  a  stimulation  at  the 
moment  of  section.  On  dividing  one  vagus,  respiration  became 
slightly  slower  and  deeper ;  on  dividing  the  second  nerve,  this  effect 
was  much  more  marked. 

On  exciting  the  central  end  of  the  divided  nerve,  inspiratory 
efforts  increased  until  at  last  the  diaphragm  came  to  a  standstill  in 
the  inspiratory  position.  But  if  a  weak  stimulus  was  employed,  the 
reverse  was  the  case ;  the  expiratory  efforts  increased,  inspiration 
becoming  weaker  and  weaker,  until  at  last  the  diaphragm  stopped  in 
the  position  of  expiration. 

These  facts  were  known  previously,  but  the  interpretation  of  them, 
in  the  light  of  further  experiments  now  to  be  described,  is  the 
following : — 

There  are  in  the  vagus  two  sets  of  fibres,  one  of  which  produces 
an  increased  activity  of  the  inspiratory  part  of  the  respiratory 
centre,  and  the  other  an  increased  activity  of  the  expiratory  part  of 
that  centre.  Stimulation  of  the  first  stops  expiration  and  produces 
inspiration ;  stimulation  of  the  second  does  the  reverse. 

The  question  now  is,  What  is  it  that  normally  produces  this 
alternate  stimulation  of  the  two  sets  of  fibres  ?  If  we  discover  this 
we  shall  discover  the  prime  moving  cause  in  the  alternation  of  the 


CH.  XXVI.] 


NERVOUS    FACTOR   IN    RESPIRATION 


379 


inspiratory  and  expiratory  acts.  It  was  sought  and  found  in  the 
alternate  distension  and  contraction  of  the  air-vesicles  of  the  lungs 
where  the  vagus  terminations  are  situated. 

In  one  series  of  experiments  positive  ventilation  was  performed; 
that  is,  air  was  pumped  repeatedly  into  the  lungs,  and  so  increased 
their  normal  distension ;  this  was  found  to  decrease  the  inspiratory 
contractions  of  the  diaphragm,  until  at  last  they  ceased  altogether, 
and  the  diaphragm  stood  still  in  the  expiratory  position  (fig.  301,  A). 

In  a  second  series  of  experiments,  negative  ventilation  was  per- 
formed ;  that  is,  the  air  was  pumped  repeatedly  out  of  the  lungs,  and 
a  condition  of  collapse  of  the  air-vesicles  produced.  This  was  found 
to  increase  the  inspiratory  contractions  of  the  diaphragm,  expiration 
became  less  and  less,  and  at  last  the  diaphragm  assumed  the  position 
of  inspiratory  standstill  (fig.  301,  B). 

Head  regards  ordinary  respiration  as  an  alternate  positive  and 
negative  ventilation,  though  not  so  excessive  as  in  the  experiments 
just  described.     Inspiration  is  positive  ventilation,  and  so  provides 
the  nervous  mechanism  of  re- 
spiration with  a  stimulus  that 
leads  to  expiration.    Expiration 
is  a  negative  ventilation,  and 
so  provides  the  stimulus  that 
leads  to  inspiration. 

We  must  naturally  be  on 
our  guard  against  regarding  the 
forcible  inflations  and  deflations 
produced  by  a  pump  as  com- 
pletely analogous  to  the  changes 
produced  in  the  lungs  by  or- 
dinary breathing ;  nevertheless, 
the  two  sets  of  impulses  are 
undoubtedly  called  into  action 
if  the  respiratory  processes  are 
sufficiently  energetic,  and  of 
the  two  sets  of  impulses,  those 
which  are  started  by  the  inspiratory  movement  play  a  more  active 
part  in  the  regulation  of  respiration  than  those  started  by  the  expira- 
tory movement,  so  much  so  that  in  unlaboured  breathing  they  alone 
need  be  considered. 

Apncea. — If  positive  and  negative  ventilation  are  used  together 
rapidly  and  alternately  at  a  rate  quicker  than  the  respiratory  rhythm, 
both  inspiratory  and  expiratory  processes  are  inhibited,  and  the  respira- 
tion ceases  for  a  short  time.  This  follows  naturally  from  the  experi- 
ments previously  described.  This  can  be  done  on  an  animal  with  a 
pair  of  bellows  fixed  to  a  tube  in  the  trachea ;  or  voluntarily  by  one- 


.  301. — Tracings  of  diaphragm.  The  upward  move- 
ments of  the  tracings  represent  inspiration ;  the 
downward  movements,  expiration.  A,  result  of 
positive,  B,  of  negative  ventilation.  (After  Head.) 


360  RESPIRATION  [CH.  XXVI. 

self  taking  a  number  of  deep  breaths  rapidly.  This  condition,  called 
apncea,  is  not  due,  as  at  one  time  supposed,  to  over-oxygenation  of  the 
blood,  but  is,  according  to  Head,  produced  reflexly ;  for  under  normal 
circumstances  arterial  blood  is  almost  fully  oxygenated.  Apnoea  is 
observed  if  inert  gases,  such  as  nitrogen  or  hydrogen,  are  used 
instead  of  air.  The  pause,  however,  is  then  shorter,  as  the  blood 
becomes  venous,  and  in  a  short  time  stimulates  the  respiratory  centre 
to  activity. 

Under  abnormal  circumstances,  namely,  after  division  of  the  vagi, 
apnoea  obviously  cannot  be  due  to  such  reflex  action.  Fredericq 
holds  that  even  ordinary  apnoea  has  a  chemical  rather  than  a  nervous 
origin.  He  attributes  it,  however,  not  to  over-oxygenation,  but  to  a 
lessening  of  the  carbonic  acid  in  the  blood. 

3.   The  Chemical  Factor  in  Respiration. 

A  consideration  of  apnoea  thus  leads  us  to  the  study  of  the 
chemical  stimuli  that  play  their  part  in  the  respiratory  process. 
Their  importance  has  been  recently  demonstrated  by  Haldane  and 
Priestley. 

In  the  first  place,  they  introduced  the  new  and  simple  method 
of  obtaining  the  composition  of  the  air  in  the  alveoli,  described 
on  p.  372.  They  found  that,  under  constant  atmospheric  pressure, 
in  man  the  alveolar  air  contains  a  nearly  constant  percentage  of 
carbon  dioxide  in  the  same  person.  In  different  individuals  this 
percentage  varies  somewhat,  but  averages  51  per  cent,  of  an  atmos- 
phere in  men,  and  4'7  in  women  and  children. 

With  varying  atmospheric  pressures,  the  percentage  varies 
inversely  as  the  atmospheric  pressure,  so  that  the  pressure  or  tension 
of  the  carbon  dioxide  remains  constant.  The  oxygen  pressure, 
however,  varies  widely  under  the  same  conditions. 

These  observations  and  the  next  to  be  immediately  described 
furnish  the  chemical  key  to  the  cause  of  the  amount  of  pulmonary 
ventilation,  and  play  an  important  part  in  conjunction  with  the 
respiratory  nervous  system  in  the  regulation  of  breathing.  For  the 
respiratory  centre  is  not  only  affected  by  the  impulses  reaching  it  by 
the  vagi  and  other  afferent  nerves,  but  it  is  also  very  sensitive  to 
any  rise  in  the  tension  of  carbon  dioxide  in  the  blood  that  supplies 
it.  The  changes  in  the  tension  of  this  gas  in  the  arterial  blood  are 
normally  proportional  to  the  changes  in  the  carbon  dioxide  pressure 
in  the  alveoli,  and  the  changes  in  the  lung  alveoli  are  transmitted  to 
the  respiratory  centre  by  the  blood.  They  found  that  a  rise  0'2  per 
cent,  in  the  alveolar  carbon  dioxide  pressure  is  sufficient  to  double 
the  amount  of  alveolar  ventilation  during  rest.  During  sudden 
muscular  work  the  alveolar  carbon  dioxide  pressure  increases  slightly, 
and  the  pulmonary  ventilation  is  consequently  increased.  Most 


CH.  XXVI.]  THE   CHEMICAL  FACTOR   IN   RESPIRATION  381 

physiologists  consider  that  the  action  of  carbonic  acid  is  not  specific, 
but  that  other  acids  can  act  in  the  same  way.  As  the  result  of 
prolonged  exercise,  the  carbonic  acid  pressure  in  the  alveoli  falls 
greatly;  nevertheless  there  is  increased  pulmonary  ventilation.  This 
is  because  lactic  and  perhaps  other  acids  are  thrown  into  the  blood, 
which  raise  its  total  acidity  (hydrogen  ion  concentration),  see  p.  395. 

Changes  in  the  oxygen  pressure  within  wide  limits  have  no  such 
influence ;  the  normal  chemical  stimulus  to  respiration  is,  therefore, 
presence  of  an  increase  of  carbon  dioxide,  and  not  diminution  of 
oxygen.  If  these  limits  are  exceeded,  as  when  the  oxygen  in  the 
atmosphere  falls  below  13  per  cent.,  the  respiratory  centre  begins 
to  be  excited  by  want  of  oxygen.  It  is  probable  that  other  fatigue 
products,  such  as  sarcolactic  acid,  assist  the  carbon  dioxide  in 
stimulating  the  respiratory  centre. 

In  connection  with  the  relative  importance  of  the  nervous  and 
chemical  factors  in  breathing,  F.  H.  Scott  has  shown  that  the 
principal  respiratory  nerves  (the  pneumogastrics)  regulate  the 
rate  or  rhythm  of  the  respiratory  movements,  whilst  the  chemical 
factor  specially  regulates  the  amount  of  pulmonary  ventilation,  that 
is,  the  depth  of  the  individual  respiratory  efforts;  for  when  these 
nerves  are  divided,  a  rise  in  the  alveolar  tension  of  carbon  dioxide 
(or  great  diminution  of  the  oxygen  in  the  respired  air)  increases  the 
depth,  but  not  the  rate  of  breathing. 

To  recapitulate : — In  a  normal  respiration  the  chemical  and 
nervous  factors  would,  therefore,  appear  to  be  related  somewhat  as 
follows : — The  inspiratory  centre  makes  an  effort,  the  degree  of 
exaltation  of  the  centre,  and  therefore,  the  magnitude  of  the  effort, 
more  especially  in  the  matter  of  depth,  is  governed  by  the  tension  of 
carbonic  acid  in  the  blood,  but  it  is  cut  short  by  an  inhibitory 
impulse  passing  up  the  vagus,  only  to  begin  again  when  the  effects 
of  this  inhibitory  impulse  are  removed. 

During  foetal  life  the  need  of  the  embryo  for  oxygen  is  small,  and  is  amply  met 
by  the  transference  of  oxygen  from  the  maternal  blood  through  the  thin  walls  of 
the  foetal  capillaries  in  the  placenta.  But  when  the  child  is  born,  this  source  of 
oxygen  is  no  longer  available,  and  the  increasing  venosity  of  the  blood  stimulates 
the  respiratory  centre  to  action,  and  is  the  essential  cause  of  the  first  inspiratory 
eiforts  the  new-born  child  makes  to  obtain  the  oxygen  it  requires.  It  is  said  that 
if  the  placental  circulation  is  stopped  while  the  child  is  still  in  utero,  respiratory 
eiforts  are  also  made.  Some  regard  the  action  of  the  air  on  the  body  surface  as  an 
accessory  cause  of  the  first  respirations,  and  it  is  the  practice  to  increase  this  in 
feeble  children  by  stimulating  the  cutaneous  nerves  by  the  application  of  cold 
water  to  the  skin.  Such  treatment  always  causes  deep  inspirations,  even  in  the 
adult.  There  are  other  nerves  stimulation  of  which  influences  the  respiratory 
act ;  for  instance,  stimulation  of  the  central  end  of  the  glossopharyngeal  inhibits 
the  respiratory  movements  for  a  short  period ;  this  accounts  for  the  very  necessary 
cessation  of  breathing  during  swallowing.  Stimulation  of  the  central  end  of  the  cut 
superior  laryngeal  nerve,  or  of  its  terminations  in  the  mucous  membrane  of  the 
larynx,  as  when  a  crumb  is  "  swallowed  the  wrong  way,"  produces  an  increase  of 
expiratory  efforts,  culminating  in  coughing. 


382  RESPIRATION  [CH.  XXVI. 

Special  Respiratory  Acts. 

Coughing. — In  the  act  of  coughing  there  is  first  of  all  a  deep  in- 
spiration, followed  by  an  expiration ;  but  the  latter,  instead  of  being 
easy  and  uninterrupted,  as  in  normal  breathing,  is  obstructed,  the 
glottis  being  momentarily  closed  by  the  approximation  of  the  vocal 
cords.  The  abdominal  muscles,  then  strongly  acting,  push  up  the 
viscera  against  the  diaphragm,  and  thus  make  pressure  on  the  air  in 
the  lungs  until  its  tension  is  sufficient  to  noisily  open  the  vocal  cords 
which  oppose  its  outward  passage.  In  this  way  considerable  force  is 
exercised,  and  mucus  or  any  other  matter  that  may  need  expulsion 
from  the  air-passages  is  quickly  and  sharply  expelled  by  the  out- 
streaming  current  of  air.  The  act  is  a  reflex  one,  the  sensory  surface 
which  is  excited  being  the  mucous  membrane  of  the  larynx,  and  the 
superior  laryngeal  nerve  is  the  afferent  nerve;  stimulation  of  other 
parts  of  the  respiratory  mucous  membrane  will  also  produce  cough, 
and  the  point  of  bifurcation  of  the  trachea  is  specially  sensitive. 
Other  sensory  surfaces  may  also  act  as  the  "signal  surface"  for  a 
cough.  Thus,  a  cold  draught  on  the  skin,  or  tickling  the  external 
auditory  meatus,  in  some  people  will  set  up  a  cough. 

Sneezing. — The  same  remarks  that  apply  to  coughing  are  almost 
exactly  applicable  to  the  act  of  sneezing;  but,  in  this  instance,  the 
blast  of  air,  on  escaping  from  the  lungs,  is  directed,  by  an  instinctive 
contraction  of  the  pillars  of  the  fauces  and  descent  of  the  soft 
palate,  chiefly  through  the  nose,  and  any  offending  matter  is  thence 
expelled. 

The  "  signal  surface  "  is  usually  the  nasal  mucous  membrane,  but 
here,  as  in  coughing,  other  causes  (such  as  a  bright  light)  will  some- 
times set  the  reflex  going. 

Hiccough  is  an  involuntary  sudden  contraction  of  the  diaphragm, 
causing  an  inspiration  which  is  suddenly  arrested  by  the  closure  of  the 
glottis,  causing  a  characteristic  sound.  It  arises  from  gastric  irritation. 

Snoring  is  due  to  vibration  of  the  soft  palate. 

Soiling  consists  of  a  series  of  convulsive  inspirations  at  the  moment 
of  which  the  glottis  is  partially  closed. 

Sighing  and  Yawning  are  emotional  forms  of  inspiration,  the  latter 
associated  with  stretching  movements  of  jaws  and  limbs.  They  appear 
to  be  efforts  of  nature  to  correct,  by  an  extra  deep  inspiration,  the 
venosity  of  the  blood  due  to  inactivity  produced  by  ennui  or  grief. 
Their  contagious  character  is  due  to  sympathy. 

There  are  many  other  abnormalities  of  the  respiratory  mechanism 
which  will  become  familiar  to  the  student  of  medicine  during  his 
clinical  studies.  We  may  mention  as  examples :  laryngismus  stri- 
dulus  (the  spasmodic  croup  of  children) ;  this  is  a  nervous  affection 
due  to  increased  reflex  irritability  of  the  laryngeal  mechanism ;  the 


CH.  XXVI.] 


ARTIFICIAL   RESPIRATION 


383 


fits  of  suffocation  are  produced  by  tonic  spasm  of  the  adductor 
muscles  of  the  glottis.  Asthma  is  another  nervous  affection,  and 
has  been  already  briefly  referred  to  on  p.  349.  Whooping-cough  is  an 
infectious  disease,  the  poison  of  which  also  acts  on  the  nervous 
respiratory  system. 


FIG.  302. — This  illustrates  the  two  principal  positions  A  and  B  in  performing  Schiifer's  method 
of  artificial  respiration. 


Artificial  Respiration. 

In  experiments  on  animals  in  which  it  is  necessary  to  open  the 
chest,  life  can  be  maintained  by  pumping  air  into  the  lungs ;  this  is 
done  by  means  of  some  form  of  pump  or  bellows,  the  delivery  tube 
of  which  is  connected  to  the  trachea  by  a  cannula,  a  side  hole  in 


384  RESPIRATION  [OH.  XXVI. 

which  provides  for  the  escape  of  the  expired  air.     A  bottle  contain- 
ing the  anaesthetic  is  placed  on  the  course  of  the  delivery  tube. 

Artificial  respiration  is  sometimes  necessary  in  man  to  restore 
normal  breathing,  as  for  instance  in  those  who  are  apparently  dead 
from  drowning.  In  such  cases  speed  in  commencing  the  artificial 
breathing,  and  perseverance  in  continuing  the  process  are  essential. 
Many  have  been  restored  to  life  after  the  efforts  have  been  continued 
for  an  hour  or  more.  It  is  now  recognised  that  of  the  numerous 
methods  for  performing  artificial  respiration,  that  recently  introduced 
by  Schafer  is  the  simplest,  least  injurious,  and  most  effective.  The 
subject  is  laid  on  the  ground  in  the  prone  position,  with  a  thick 
folded  garment  under  his  chest.  The  operator  kneels  by  his  side 
or  athwart  him  facing  his  head,  and  places  his  hands  on  each  side 
over  the  lower  ribs.  He  slowly  throws  the  weight  of  his  body 
forwards,  and  thus  presses  upon  the  thorax  of  the  subject,  and 
forces  air  out  of  the  lungs  (fig.  302,  A)  ;  he  then  gradually  relaxes 
the  pressure  by  bringing  his  body  up  again,  but  without  removing 
his  hands  (fig.  302,  B).  This  is  repeated  regularly  at  the  rate  of 
twelve  to  fifteen  times  a  minute  until  normal  respiration  begins,  or 
until  all  hope  of  restoration  is  given  up. 

Ventilation. 

Some  observers  have  stated  that  certain  noxious  substances  are 
ordinarily  contained  in  expired  air  which  are  much  more  poisonous 
than  carbonic  acid,  but  more  careful  researches  have  failed  to  sub- 
stantiate this.  If  precautions  be  taken  by  absolute  cleanliness  to 
prevent  admixture  of  the  air  with  exhalations  from  skin,  teeth,  and 
clothes,  the  expired  air  only  contains  one  noxious  substance,  and  that 
is  carbonic  acid. 

Absolute  cleanliness  is,  however,  not  the  rule;  and  the  air  of 
rooms  becomes  stuffy  when  the  amount  of  expired  air  in  them  is  just 
so  much  as  to  raise  the  percentage  of  carbonic  acid  to  0-1  per  cent. 
An  adult  gives  off  about  0-6  cubic  feet  of  carbonic  acid  per  hour,  and 
if  he  is  supplied  with  1000  cubic  feet  of  fresh  air  per  hour,  he  will 
add  0-6  to  the  0-4  cubic  feet  of  carbonic  acid  it  already  contains;  in 
other  words,  the  percentage  of  that  gas  will  be  raised  to  0-1.  An 
hourly  supply  of  2000  cubic  feet  of  fresh  air  will  lower  the  percentage 
of  carbonic  acid  to  0-07,  and  of  3000  cubic  feet  to  0-06,  and  this  is 
the  supply  which  is  usually  recommended.  In  order  that  the  air  may 
be  renewed  without  giving  rise  to  draughts,  each  adult  should  be 
allotted  sufficient  space  in  a  room,  at  least  1000  cubic  feet. 

Leonard  Hill  has  recently  stated  that  the  effects  of  bad  ventilation 
are  not  so  much  due  to  changes  in  the  chemical  composition  of  the 
air,  as  to  the  absence  of  movement  in  the  air ;  moving  air  has  a 
stimulating,  and  still  air  a  depressing  effect. 


CHAPTEE  XXVII 

THE  RELATION    OF  RESPIRATION   TO   OTHER   PROCESSES   IN   THE  BODY 

WE  shall  in  this  chapter  treat  of  the  relationship  between  respira- 
tion and  the  circulation,  and  between  respiration  and  metabolism, 
and  in  conclusion  deal  with  certain  pathological  conditions,  which 
are  important  for  the  light  they  throw  upon  physiological  processes. 

The  Effect  of  Respiration  on  the  Circulation. 

The  main  effect  of  respiration  on  the  circulation  is  shown  in  the 
accompanying  figure  (fig.  303).     It  will  be  noticed  that  the  arterial 


Fia.  303. — Comparison  of  blood-pressure  curve  with  curve  of  intra-thoracic  pressure.  (To  be  read  from 
left  to  right.)  a  is  the  curve  of  blood-pressure  with  .its  respiratory  undulations,  the  slower  beats 
on  the  descent  being  very  marked ;  b  is  the  curve  of  intra-thoracic  pressure  obtained  by  connecting 
one  limb  of  a  manometer  with  the  pleural  cavity.  Inspiration  begins  at  i  and  expiration  at  e. 
The  intra-thoracic  pressure  rises  very  rapidly  after  the  cessation  of  the  inspiratory  effort,  and  then 
slowly  falls  as  the  air  issues  from  the  chest ;  at  the  beginning  of  the  inspiratory  effort  the  fall 
becomes  more  rapid.  (M.  Foster.) 

pressure  rises  with  inspiration  and  falls  with  expiration,  but  that  the 
two  events  are  not  quite  synchronous,  the  rise  of  pressure  beginning  a 
little  later  than  the  inspiratory  act,  and  the  fall  a  little  later  than 
the  expiratory  act. 

It  will  also  be  scon  that  the  heart  beats  more  rapidly  during  tho 

385  2    B 


386  RELATION   OF  .RESPIRATION   TO   OTHER    PROCESSES    [CH.  XXVII. 

rise  of  blood-pressure  than  during  the  fall.  This  difference  disappears 
when  the  vagi  are  cut.  Bespiratory  undulations,  however,  are  still 
present,  though  not  so  marked  as  before ;  hence  the  cardiac  variations 
are  not  their  sole  cause.  They  are  chiefly  the  result  of  the  mechanical 
conditions  dependent  on  the  lungs  and  heart  with  its  large  vessels 
being  contained  within  the  air-tight  thorax.  When  the  capacity  of 
the  chest  is  increased  in  inspiration,  the  tension  of  the  lung  tissue 
due  to  its  greater  expansion  is  increased ;  hence  the  difference  between 
the  intra-pleural  pressure  and  that  in  the  lungs  (which  is  atmos- 
pheric) becomes  more  marked,  for  the  difference  of  pressure  is  to  be 
measured  by  the  elastic  force  of  the  lung  tending  to  produce  its 
collapse.  If  the  intra-thoracic  pressure  is  measured,  it  is  found  that 
it  varies  from  —  5  to  —  7  mm.  of  mercury  at  the  end  of  expiration  to 
—  30  at  the  end  of  a  deep  inspiration ;  that  is  to  say,  from  5  to  7  to 
30  mm.  less  than  the  atmospheric  pressure  (760  mm.  of  mercury). 
The  pressure  outside  the  heart  and  large  thoracic  vessels  is  corre- 
spondingly diminished  during  inspiration  to  the  same  extent,  and  pro- 
duces its  main  effect  (distension)  upon  the  veins  because  they  are  never 
fully  distended,  and  because  the  pressure  within  them  is  low.  This 
increase  in  the  "  pressure  gradient "  (i.e.,  the  rate  of  fall  of  pressure) 
between  the  intra-  and  eatfra-thoracic  great  veins  results  in  a  pro- 
portionately more  rapid  flow  of  blood  into  the  thorax,  and  therefore 
into  the  right  side  of  the  heart ;  for  within  certain  limits  the  right 
heart  can  be  easily  expanded  more  fully  if  a  greater  supply  of  blood 
is  provided.  Consequently,  the  output  from  the  right  side  of  the  heart 
increases,  and  thus  via  the  pulmonary  circuit  the  inflow  into  the  left 
side  of  the  heart  is  increased ;  in  its  turn,  therefore,  the  output  from 
the  left  ventricle  rises,  and  so  the  aortic  pressure  is  raised.  This 
effect  would  be  counteracted  if  the  aorta  and  its  branches  within  the 
thorax  were  as  easily  affected  by  changes  of  the  intra-thoracic  pressure 
as  are  the  thin-walled  and  easily  distensible  veins  ;  the  thick  wall  of 
the  aorta  and  its  branches,  however,  prevents  them  from  undergoing 
much  change  of  this  kind  during  ordinary  breathing.  The  conditions 
in  the  veins  are  reversed  when,  with  the  expiratory  act,  the  thorax 
returns  to  its  former  size ;  therefore  the  arterial  blood-pressure  falls. 

The  effect  of  inspiration  on  arterial  blood-pressure  is  at  first 
assisted  by  the  pressure  of  the  diaphragm,  as  it  descends,  on  the 
abdominal  veins,  and  blood  is  thus  sent  upwards  into  the  chest  by 
the  vena  cava  inferior.  On  the  other  hand,  this  is  to  some  extent 
counterbalanced  by  the  obstruction  in  the  passage  of  the  blood 
downwards  in  the  abdominal  aorta,  and  upwards  from  the  veins  of 
the  lower  extremities,  but  again  the  veins  are  the  vessels  more  easily 
influenced  by  moderate  changes  in  external  pressure. 

We  thus  see  that  these  various  physical  conditions  produce  during 
inspiration  an  increased  flow  of  blood  into  the  right  heart ;  this 


CH.  XXVII.]          EFFECT   OF  KESPIRATION   ON   CIKGULATION  38? 

increased  supply  of  blood  is  then  passed  via  the  pulmonary  circuit  to 
the  left  heart ;  this  takes  a  little  time ;  hence  it  is  that  the  effect  oi' 
inspiration  in  raising  arterial  pressure  is  not  seen  at  the  very  com- 
mencement of  the  inspiration.  In  fact,  in  some  animals  which 
normally  breathe  very  quickly  (for  instance,  the  rabbit),  inspiration 
is  over,  and  the  next  expiration  has  begun  before  the  rise  of  blood- 
pressure  occurs.  By  making  a  rabbit  breathe  slowly  (Fredericq 
accomplished  this  by  cooling  the  medulla  oblongata),  the  tracing 
obtained  is  similar  to  that  which  is  got  from  an  animal  like  a  dog, 
which  normally  breathes  slowly. 

The  delay  which  occurs  in  the  inspiratory  rise  of  arterial  blood-pressure  has 
been  attributed  by  some  to  an  increase  of  the  capacity  of  the  pulmonary  capillaries 
brought  about  by  the  distension  of  the  chest ;  this  sudden  increase  in  the  bed  of 
the  stream  would  temporarily  retard  the  rate  of  flow  through  the  pulmonary 
circuit.  Recent  research  has,  however,  shown  that  even  considerable  changes  in 
the  capacity  of  the  blood-vessels  of  the  lung,  as,  for  instance,  by  shutting  off  the 
entire  circulation  of  one  lung  (Tigerstedt),  have  little  or  no  influence  on  the 
systemic  pressure  ;  it  is  therefore  extremely  doubtful  whether  small  changes  such 
as  would  be  produced  in  ordinary  breathing  can  have  any  effect  on  the  inflow  into 
the  left  auricle. 

When  the  chest  of  an  animal  is  freely  opened,  and  artificial 
respiration  performed  in  order  to  keep  it  alive,  respiratory  undulations 
on  the  arterial  pressure-curve  are  still  seen,  but  they  are  in  the 
reverse  direction.  These  obviously  cannot  be  produced  in  the 
mechanical  way  just  described.  The  forcible  inflation  with  air  at 
first  squeezes  more  blood  out  of  the  alveolar  capillaries,  that  is,  the 
capacity  of  these  vessels  is  diminished,  and  this  theoretically  might 
increase  the  quantity  of  blood  thrown  into  the  left  ventricle,  and  so 
cause  a  rise  of  arterial  pressure.  But  the  main  effect  of  increased 
mtra-alveolar  pressure  is  to  produce  an  increased  resistance  to  the  pul- 
monary circulation,  and  the  rate  of  flow  into  the  left  side  consequently 
falls ;  the  aortic  pressure  therefore  falls,  while  the  pressure  in  the  pul- 
monary artery  rises.  If  the  high  positive  intrapulmonary  air- 
pressure  persisted,  a  condition  would  soon  be  reached,  in  which  the 
increased  blood-pressure  in  the  pulmonary  artery  would  lead  to  a 
greater  flow,  and  the  aortic  blood-pressure  would  remain  constant ;  this, 
however,  has  been  shown  to  take  a  much  longer  time  than  an  ordinary 
respiration  period.  Hence  the  effect  of  inflations  of  the  lungs  at  the 
ordinary  respiration  rate  is  to  diminish  the  aortic  blood-pressure; 
this  rises  again,  for  the  opposite  reasons,  in  the  intervals  of  deflation 
which  correspond  to  expiration. 

If  artificial  respiration  is  performed  while  the  thorax  is  not  opened, 
a  further  complication  arises  from  the  fact  that  the  increased  intra- 
pleural  pressure  decreases  the  rate  of  flow  of  blood  into  the  thorax, 
and  under  these  conditions  the  blood-pressure  in  the  pulmonary 
artery  falls,  and  in  consequence  the  fall  in  the  aortic  blood-pressure 


388  RELATION   OF  RESPIRATION   TO   OTHER   PROCESSES     [GIL  XXVII. 

becomes  more  marked  with  each   inflation  than  it  does  when  the 
thorax  is  open. 

The  last  point  of  detail  we  have  to  consider  is  the  cause  of  the 
greater  frequency  of  the  heart  during  the  inspiratory  phase,  a 
phenomenon  which  is  evidently  due  to  lessening  of  vagus  action, 
since  the  inequality  of  the  heart-rate  disappears  when  the  vagi  are 
cut.  The  question  before  us  is,  What  is  the  cause  of  the  rhythm  in 
the  activity  of  the  vagus  centre  ?  There  appear  to  be  two  factors 
concerned  in  its  causation :  one  is  a  reflex  action,  the  other  is  what 
may  be  termed  a  central  overflow.  We  will  consider  these  separately. 

1.  The  reflex.    Stimulation  of  the  pulmonary  branches  of  the  vagus 
by  electrical  stimuli,  or  of  their  terminations  in  the  alveoli  by  certain 
irritating  vapours  such  as  bromine,  causes  a  reflex  inhibition  of  the 
heart ;  great  distension  of  the  alveoli  has  a  similar  effect,  but  moderate 
distension,  such  as  occurs  in  an  ordinary  inspiration,  has  the  opposite 
reflex  effect,  causing  the  heart  to  beat  more  rapidly.     The  afferent 
fibres  from  the  pulmonary  alveoli  enter  the  bulb  by  the  upper  set  of 
the  rootlets  of  the  combined  glossopharyngeal- vagus-spinal  accessory 
nucleus  (the  a  group,  p.  249).    Sometimes  the  rootlets  of  this  group  are 
three  in  number,  sometimes  two.      When  there  are  two,  the  lower 
rootlet,  when  there  are  three,  the  lower  two  rootlets,  contain  the  fibres 
in  question  (Cadman). 

2.  The  overflow.    The  respiratory  centre  exhibits  alternate  phases 
of  activity,  or  what  is  termed  a  rhythmical  action.      It  is  in  close 
anatomical  connection  with  two  other  important  centres  in  the  bulb, 
namely,  the  cardio-inhibitory  and  the  vaso-motor  centres.     Consider- 
ing how  closely  these  three  centres  are  connected  by  association 
fibres,  it  is  not  surprising  that  the  cells  of  the  two  latter  centres 
should  be  affected    by  the   rhythm  of  the  cells  of  the  respiratory 
centre,  and  the  term  overflow  is  an  expression  that  roughly  indicates 
what  occurs.     This  overflow  from  the  respiratory  centre  affects  its 
two  neighbours  in  the  same  way.     During  inspiration  the  activity 
of  both  the  cardio-inhibitory  centre  and  of  the  vaso-motor  centre  is 
diminished,  hence  the  heart  beats  faster.     The  factor  which  we  have 
termed  the  overflow  is  more  important  than  that  which  we  have 
described  as  the  reflex. 

These  facts  show  us  that  the  parallelism  of  the  respiratory  and 
arterial  pressure -curves  is  not  merely  the  result  of  the  mechanical 
conditions  already  described,  though  these  are  the  most  important. 
But  in  the  normal  condition  with  the  thorax  closed,  and  the  vagi 
uncut,  certain  nervous  factors  come  also  into  play. 

Valsalva's  Experiment. — In  speaking  of  the  effects  of  expiration, 
we  have  considered  only  ordinary  quiet  expiration.  With  forced 
expiration,  there  is  considerable  impediment  to  the  circulation ;  this 
is  markedly  seen  in  what  is  called  Yalsalva's  experiment.  This  con- 


CH.  XXVII.]  ASPHYXIA  389 

sists  in  making  a  forced  expiratory  effort  with  the  mouth  and  nose 
shut ;  the  effects  are  most  marked  in  people  with  an  easily  compres- 
sible thorax.  By  such  an  act  the  intrathoracic  and  abdominal 
pressures  rise  so  greatly  that  the  outlets  of  the  veins  of  the  limbs, 
head,  and  neck  into  the  thorax  are  blocked.  At  first,  the  blood  in 
the  abdominal  veins  is  drawn  on  into  the  right  heart ;  this  produces 
a  slight  rise  of  arterial  pressure ;  but  soon,  if  the  effort  is  continued, 
the  lungs  are  emptied  of  blood,  the  filling  of  the  right  heart  is 
opposed,  and  the  blood  is  dammed  back  in  the  peripheral  veins,  where 
the  pressure  rises  to  mean  arterial  pressure.  The  arterial  pressure 
begins  then  to  fall;  but  before  any  considerable  fall  occurs,  the 
expiratory  effort  ceases  from  exhaustion  of  the  subject  of  the  experi- 
ment, and  a  deep  inspiration  is  taken.  During  this  inspiration,  the 
blood  delivered  by  the  right  heart  is  all  used  in  the  filling  of  the 
comparatively  empty  pulmonary  vessels ;  thus  several  beats  of  the 
left  ventricle  become  abortive,  and  produce  no  effect  on  the  radial 
artery ;  the  face  blanches,  and  the  subject  becomes  faint  from  cerebral 
anaemia. 

Asphyxia. 

Asphyxia  may  be  produced  in  various  ways:  for  example,  by 
the  prevention  of  the  due  entry  of  oxygen  into  the  blood,  either  by 
direct  obstruction  of  the  trachea  or  other  part  of  the  respiratory 
passages,  or  by  introducing  instead  of  ordinary  air  a  gas  devoid  of 
oxygen,  or  by  interference  with  the  due  interchange  of  gases  between 
the  air  and  the  blood. 

The  symptoms  of  asphyxia  may  be  roughly  divided  into  three 
stages :  (1)  the  stage  of  exaggerated  breathing ;  (2)  the  stage  of  con- 
vulsions ;  (3)  the  stage  of  exhaustion. 

In  the  first  stage  the  breathing  becomes  more  rapid,  and  at  the 
same  time  deeper  than  usual,  inspiration  at  first  being  especially 
exaggerated  and  prolonged.  The  muscles  of  extraordinary  inspiration 
are  called  into  action,  and  the  effort  to  respire  is  laboured  and  painful. 
This  is  soon  followed  by  a  similar  increase  in  the  expiratory  efforts, 
which  become  excessively  prolonged,  being  aided  by  all  the  muscles 
of  extraordinary  expiration.  During  this  stage,  which  lasts  a  vary- 
ing time  from  a  minute  upwards,  according  as  the  deprivation  of 
oxygen  is  sudden  or  gradual,  the  lips  become  blue,  the  eyes  are 
prominent,  and  the  expression  intensely  anxious.  The  prolonged 
respirations  are  accompanied  by  a  distinctly  audible  sound;  the 
muscles  attached  to  the  chest  stand  out  as  distinct  cords.  This  stage 
includes  the  two  conditions  hyperpncea  (excessive  breathing)  and 
dyspnoea  (difficult  breathing),  which  follows  later.  It  is  due  to  the 
increasingly  powerful  stimulation  of  the  respiratory  centre  by  the 
increasingly  venous  blood,. 


390     RELATION  OF  RESPIRATION  TO  OTHER  PROCESSES   [CH.  XXVII. 

In  the  second  stage,  which  is  not  marked  by  any  distinct  line  of 
demarcation  from  the  first,  the  violent  expiratory  efforts  become 
convulsive,  and  then  give  way,  in  men  and  other  warm-blooded 
animals,  to  general  convulsions,  which  arise  from  the  further  stimula- 
tion of  the  centres  in  brain  and  cord  by  venous  blood.  Spasms  of 
the  muscles  of  the  body  in  general  occur,  and  not  of  the  respiratory 
muscles  only.  The  convulsive  stage  is  a  short  one,  and  lasts  less 
than  a  minute. 

The  third  stage,  or  stage  of  exhaustion.  In  it  the  respirations  all 
but  cease,  the  spasms  give  way  to  flaccidity  of  the  muscles,  there  is 
insensibility,  the  conjunctivas  are  insensitive  and  the  pupils  are 
widely  dilated.  Every  now  and  then  a  prolonged  sighing  inspiration 
takes  place,  at  longer  and  longer  intervals,  until  breathing  ceases 
altogether,  and  death  ensues.  During  this  stage  the  pulse  is  scarcely 
to  be  felt,  but  the  heart  may  beat  for  some  seconds  after  the  respira- 
tion has  stopped.  The  condition  is  due  to  the  gradual  paralysis  of 
the  centres  by  the  prolonged  action  of  the  venous  blood.  This  stage 
may  last  three  minutes  and  upwards. 

After  death  from  asphyxia  it  is  found  in  the  great  majority  of 
cases  that  the  right  side  of  the  heart,  the  pulmonary  arteries,  and 
the  systemic  veins  are  gorged  with  dark,  almost  black,  blood,  and 
the  left  side  of  the  heart,  the  pulmonary  veins,  and  the  arteries  are 
empty.  The  explanation  of  these  appearances  may  be  thus  summar- 
ised :  when  oxygenation  ceases,  venous  blood  at  first  passes  freely 
through  the  lungs  to  the  left  heart,  and  so  to  the  great  arteries. 
Owing  to  the  stimulation  of'  the  vaso-motor  centres  by  the  venous 
blood,  the  arterioles,  particularly  those  of  the  splanchnic  area, 
are  constricted;  the  arterial  blood-pressure  therefore  rises,  and  the 
left  side  of  the  heart  becomes  distended.  The  highly  venous  blood 
passes  through  the  arterioles,  and,  favoured  by  the  laboured  respira- 
tory movements,  arrives  at  the  right  side  of  the  heart,  which  it 
fills  and  distends ;  the  right  side  of  the  heart  is  becoming  feebler  at 
the  same  time,  and  therefore  unable  to  effectively  discharge  its  blood 
through  the  pulmonary  circuit.  Simultaneously  the  left  ventricle  is 
also  becoming  weakened,  and  therefore  its  suction  action  diminishes. 
In  this  way  the  blood  is  dammed  back  in  the  right  heart  and 
veins,  and  the  left  side  of  the  heart  therefore  gets  into  the  empty 
condition  in  which  it  is  found  after  death.  Some  consider  that  the 
early  onset  of  rigor  mortis  in  the  left  ventricle  may  be  in  part  a 
cause  of  its  contracted  and  empty  condition. 

In  the  first  and  second  stages  of  asphyxia,  the  arterial  pressure 
rises  above  the  normal ;  this  is  due  to  the  constriction  of  the  arterioles 
which  is  in  part  produced  by  the  suprarenal  glands  pouring  out  more 
adrenaline  into  the  circulation,  owing  to  their  being  stimulated  by 
the  excess  of  carbonic  acid  in  the  blood.  The  fall  of  pressure  in  the 


CH.  XXVII.] 


ASPHYXIA 


391 


last  stage  is  mainly  due  to  heart  failure.  If  the  vagi  are  not  divided 
previously,  the  rise  of  pressure  is  much  less,  and  the  heart  beats  very 
slowly :  this  enables  the  heart  to  last  longer,  and  is  due  to  excitation 


of  the  cardio-inhibitory  centre  by  venous  blood.  The  accompanying 
photograph  of  a  tracing  (fig.  304),  which  I  owe  to  Dr  C.  J.  Martin, 
shows  these  effects;  it  has  been  somewhat  reduced  in  size  for 
purposes  of  reproduction.  The  lower  tracing  is  that  of  venous 


392  RELATION   OF  RESPIRATION    TO    OTHER   PROCESSES      [oil.  XXVII. 


pressure  taken  with  a  salt  solution  manometer  from  the  jugular  vein. 
It  will  be  noticed  that  the  fall  of  arterial  pressure  is  accompanied 
with  a  great  rise  of  venous  pressure  due  to  the  venous  congestion  just 
described. 

The  Relation  of  Respiration  to  Nutrition. 

The  gaseous  interchanges  in  the  lungs  constitute  what  is  fre- 
quently termed  external  respiration.  Oxygen  obtains  an  entrance 
into  the  blood,  and  is  carried  to  the  tissues  in  the  loose  compound 
known  as  oxyhaemoglobin.  In  the  tissues,  this  compound  is  dis- 
sociated, and  the  respiratory  oxygen  is  utilised  by  the  tissue  elements 
for  the  combustion  processes  which  occur  consequent  on  their 
activity.  Of  the  ultimate  products,  carbonic  acid  and  a  portion  of 
the  water  find  an  outlet  by  the  lungs,  to  which  they  are  transported 
by  the  venous  blood.  The  gaseous  interchanges  in  the  tissues  con- 
stitute what  is  known  as  internal  or  tissue  respiration. 

Inspired  and  Expired  Air.  —  We  may  compare  the  composition  of 
the  inspired  or  atmospheric  air  with  that  of  the  expired  air  in  the 
following  table:— 


Inspired  air. 

Expired  air. 

Oxygen  . 
Nitrogen 
Carbonic  acid 
Watery  vapour 
Temperature  . 

20-96  vols.  per  cent. 
79 
0-04      „ 
variable 
»» 

16-03  vols.  per  cent. 
79 
4-4        „ 
saturated 
that  of  body  (37°  C.) 

The  chief  change  is  in  the  proportion  of  oxygen  and  carbonic  acid. 
The  loss  of  oxygen  is  about  5,  the  gain  in  carbonic  acid  about  4*5.  If 
the  inspired  and  expired  airs  are  carefully  measured  at  the  same 
temperature  and  barometric  pressure,  the  volume  of  expired  air  is  thus 
found  to  be  rather  less  than  that  of  the  inspired.*  The  conversion  of 
oxygen  into  carbonic  acid  would  not  cause  any  change  in  the  volume 
of  the  gas ;  for  a  molecule  of  oxygen  (02)  would  give  rise  to  a  molecule 
of  carbonic  acid  (C02)  which  would  occupy  the  same  volume  (Avo- 
gadro's  law).  It  must,  however,  be  remembered  that  carbon  is  not 
the  only  element  which  is  oxidised.  Fat  and  protein  contain  a 
number  of  atoms  of  hydrogen,  which,  during  metabolism,  are  oxidised 
to  form  water  ;  a  small  amount  of  oxygen  is  also  used  in  the  formation 
of  urea.  Carbohydrates  contain  sufficient  oxygen  in  their  own  mole- 
cules to  oxidise  their  hydrogen ;  hence  the  apparent  loss  of  oxygen  is 
least  when  a  vegetable  diet  (that  is,  one  consisting  largely  of  starch 

*  This  diminution  of  volume  will  cause  a  slight  rise  in  the  proportionate  volume 
of  nitrogen  per  cent. 


CH.  XXVII.] 


THE   RESPIRATORY   QUOTIENT 


393 


and  other  carbohydrates)  is  taken,  and  greatest  when  much  fat  and 
protein  are  eaten.     The  quotient   n  2  7      K    .    is  called  the  respiratory 


absorbed 


4-5 


quotient.     Normally  it  is  —^  =  0'9,  but  it  varies  considerably  with  diet, 

o 

as  just  stated. 

The  amount  of  respiratory  interchange  of  gases  is  estimated  by 
enclosing  an  animal  in  an  air-tight  chamber,  except  that  there  is  a 
tube  entering  and  another  leaving  it ;  by  one  tube  oxygen  or  air  can 
enter,  and  is  measured  by  a  gas-meter  as  it  passes  in.  The  air  is 
drawn  through  the  chamber,  and  leaves  it  by  the  other  tube ;  this  air 
lias  been  altered  by  the  respiration  of  the  animal,  and  in  it  the  car- 
bonic acid  and  water  are  estimated  ;  it  is  drawn  into  bottles  containing 
a  known  amount  of  an  alkali ;  this  combines  with  the  carbonic  acid 
and  is  increased  in  weight :  the  increase  in  weight  gives  the  amount 
of  carbonic  acid;  the  alkali  used  in  Eegnault  and  Eeiset's  apparatus 
was  potash;  Pettenkofer  used  baryta  water;  Haldano  recommends 
soda-lime.  The  water  is  estimated  in  bottles  containing  pumice 
moistened  with  sulphuric  acid. 

The  accompanying  drawing  (fig.  305)  shows  the  essential  part  of 


Fio.  305.— Haldane's  apparatus  for  estimating  the  carbonic  acid  and  aqueous  vapour  given  off  by  an 

animal. 

the  simple  but  effective  apparatus  used  by  Haldane.  The  animal  is 
placed  in  the  vessel  A ;  air  is  sucked  through  the  apparatus  (which 
must  be  perfectly  air-tight)  by  a  water-pump  at  a  suitable  rate.  The 
arrows  indicate  the  direction  in  which  the  air  passes.  It  goes  first 
through  two  Woulffs  bottles,  1  and  2.  No.  1  contains  soda-lime, 
which  frees  the  air  from  carbonic  acid ;  No.  2  contains  pumice-stone 
moistened  with  sulphuric  acid,  which  frees  the  air  from  aqueous 
vapour.  The  pure,  dry  air  next  reaches  the  animal  chamber,  and  the 
animal  gives  off  to  it  carbonic  acid  and  aqueous  vapour.  It  passes 
then  through  the  three  bottles,  3,  4,  and  5.  No.  3  contains  pumice  and 
sulphuric  acid,  which  removes  the  water ;  No.  4  contains  soda-lime, 
which  absorbs  the  carbonic  acid ;  and  No.  5  contains  pumice  and  sul- 
phuric acid,  which  absorbs  any  water  carried  over  from  bottle  4.  The 
'increase  of  weight  in  bottle  3  at  the  end  of  a  given  time  (e.g.  an  hour) 
is  the  weight  of  water  given  off  by  the  animal  in  that  time ;  the  in- 


394  RELATION   OF  RESPIRATION   TO   OTHER   PROCESSES     [CH.  XXVII. 

crease  of  weight  in  bottles  4  and  5  weighed  together  gives  the  amount 
of  carbonic  acid  produced  by  the  animal  in  the  same  time. 

Eanke  gives  the  following  numbers  from  experiments  made  on  a 
man,  who  was  taking  a  mixed  diet  consisting  of  100  grammes  of 
protein,  100  of  fat,  and  250  of  carbohydrate  in  the  twenty-four  hours. 
The  amount  of  oxygen  absorbed  in  the  same  time  was  666  grammes ; 
of  which  560  passed  off  as  carbonic  acid,  9  in  urea,  19  as  water 
formed  from  the  hydrogen  of  the  protein,  and  78  from  that  of  the  fat. 

Vierordt  from  a  number  of  experiments  on  human  beings  gives  the 
following  average  numbers :  the  amount  of  oxygen  absorbed  in  the 
twenty-four  hours  is  744  grammes ;  this  leads  to  the  formation  of  900 
grammes  of  carbonic  acid  (this  contains  about  half  a  pound  of  carbon) 
and  360  grammes  of  water. 

The  respiratory  interchange  is  lessened  during  sleep.  It  is  especi- 
ally small  in  the  winter  sleep  of  hibernating  animals.  During  hiber- 
nation the  respiratory  quotient  sinks  to  0'5,  so  that  the  animals 
actually  gain  weight  from  retention  of  oxygen.  This  aspect  of  respira- 
tion is  essentially  so  much  a  part  of  "  metabolism  "  that  it  will  be  dealt 
with  more  in  detail  in  the  chapters  which  deal  with  that  subject. 
(See  especially  the  respiration  calorimeter  in  Chap.  XLTI.) 

Tissue  Respiration. — As  has  been  already  stated,  respiration 
may  be  divided  into  internal  or  tissue  respiration  and  external  or 
pulmonary  respiration.  External  respiration  is  much  the  less 
obscure,  and  we  have  treated  of  it  at  considerable  length,  not  only 
on  this  account,  but  also  on  account  of  the  very  frequent  impair- 
ments of  the  pulmonary  mechanism  which  are  met  with  in  disease. 
It  must  be  borne  in  mind,  however,  that  pulmonary  respiration  is 
but  the  means,  and  tissue  respiration  is  the  end. 

Tissue  respiration  consists  in  the  passage  of  oxygen  from  the 
blood  of  the  capillaries  to  the  cells  of  the  tissues,  and  the  passage 
of  carbonic  acid  in  the  reverse  direction.  This  gaseous  interchange 
is  no  doubt  brought  about  by  a  simple  process  of  diffusion.  The 

oxygen  passes  out  of  the  plasma 
of  the  blood  through  the  capillary 
wall,  and  then  through  the  lymph 
,  ,  until  it  reaches  the  cell  in  which 

(iJIfliM  it  is  going    to   be   used,   which 

we  will  suppose  is  a  muscle  fibre 
FIG.  BOG.  (fig.  306).     In  order  that  a  con- 

stant stream  of  oxygen  may  pass 

from  the  blood  to  the  fibre,  there  must  be  a  difference  of  oxygen 
pressure  between  the  oxygen  dissolved  in  the  plasma,  and  that 
dissolved  in  the  lymph,  and  the  latter^must  be  at  a  greater  pressure 
than  that  dissolved  in  the  muscle  fibre.  The  amount  of  oxygen 
which  passes  will,  other  things  being  equal,  be  directly  proportional 


CH.  XXVII.]  TISSUE   RESPIRATION  395 

to  these  pressure  differences,  and  as  the  amount  varies  greatly  at 
different  times,  it  is  obvious  that  the  pressure  differences  vary 
greatly  also.  When  the  muscle  is  at  rest,  the  oxygen  pressure  in 
the  capillaries  is  very  near  to  that  in  the  muscle  fibre ;  when  the 
muscle  is  active  and  using  large  quantities  of  oxygen,  the  intra- 
capillary  oxygen  pressure  is  much  greater  than  the  intra-muscular 
oxygen  pressure.  Such  a  change  might  be  brought  about  by  a  rise 
in  the  intra-capillary  oxygen  pressure,  or  a  fall  in  the  intra-muscular 
oxygen  pressure,  or  by  both  taking  place  simultaneously.  Let  us 
therefore  enquire  what  is  known  about  these  quantities. 

The  tension  of  oxygen  in  muscle  has  recently  been  calculated 
as  being  at  most  equal  to  19  mm.  of  mercury;  from  this  it  may 
vary  down  to  zero.  Within  these  limits  the  conditions  for  diffusion 
can  be  increased  by  a  drop  in  the  intra-muscular  oxygen  pressure. 

There  is,  in  addition,  a  mechanism  for  raising  the  intra-capillary 
oxygen  pressure.  This  is  the  increased  quantity  of  acid  (carbonic 
and  sarco-lactic  acids)  which  is  thrown  into  the  blood  as  the  result 
of  muscular  metabolism.  The  following  diagram  (fig.  307)  shows 
the  extent,  both  in  degree  and  time,  of  this  pouring  of  acid  into  the 
blood  as  the  result  of  a  tetanic  contraction  of  a  muscle  lasting  only 
a  few  seconds. 


10       30      50      70      90      110       130     J50     170      1913     210     230     250     270     290 

— »  Time  In  seconds. 

FIG.  307. — The  black  area  represents  the  lactic  acid  thrown  into  the  blood  during  the  time  following 
a  tetanus  that  lasted  84  seconds;  the  work  done  by  the  muscle  was  70  gramme-centimetres;  the 
total  quantity  of  lactic  acid  formed  was  O'OOS  grammes.  The  figures  on  the  vertical  line  represent 
fractions  of  a  gramme  of  lactic  acid  per  second. 

In  glandular  structures  the  oxygen  pressure  is  higher  than 
in  muscle;  probably  owing  to  the  relatively  more  copious  blood- 
supply  of  glands,  equilibrium  is  more  readily  established  between 
the  blood  and  the  gland  cells,  the  oxygen  pressure  in  the  cells  being 
almost  that  present  in  venous  blood. 

The  quantity  of  oxygen  used  by  different  tissues  varies  not  only 
with  the  degree  of  their  activity,  but  also  with  the  nature  of  the 
tissues.  On  the  whole  it  may  be  said  that,  weight  for  weight, 
glandular  tissue  uses  most  oxygen ;  next  in  order  come  the 
muscular  tissues,  and  last  of  all,  the  connective  tissues.  There  are 
some  important  tissues,  notably  the  nervous  system,  about  which 
little  is  known  in  this  connection.  The  amount  of  oxygen  used  by 


395  RELATION    OF   RESPIRATION   TO    OTHER   PROCESSES      [oil.  XXVII. 

an  organ  or  tissue  per  gramme  per  minute  is  called  its  coefficient  of 
oxidation. 

Measurement  of  Coefficient  of  Oxidation. — The  method  adopted 
depends  upon  whether  the  observer  desires  to  ascertain  the 
coefficient  at  a  particular  moment  of  time,  or  its  average  value  over 
a  considerable  period.  If  the  former  is  desired,  it  is  necessary: — 
(1)  to  estimate  the  gases  in  the  blood  going  to  and  emerging  from 
the  organ ;  this  is  performed  by  the  chemical  method  of  expelling  the 
oxygen  and  carbonic  acid  from  samples  of  the  arterial  and  venous 
blood  by  means  of  potassium  ferricyanide  and  tartaric  acid  respec- 
tively (see  p.  364);  (2)  to  determine  the  amount  of  blood  passing 
through  the  organ  in  a  given  time,  say  one  minute ;  and  (3)  at  the 
conclusion  of  the  experiment  the  organ  is  weighed,  so  that  the 
gaseous  exchange  per  gramme  can  be  calculated. 


FIG.  308.— Tracing  to  illustrate  Brodie's  method  of  ascertaining  the  rate  of  blood-flow  through 
an  organ.     For  explanation  see  text. 

The  rate  of  the  flow  of  blood  through  an  organ  may  be  ascertained, 
either  by  directly  measuring  the  venous  blood  as  it  emerges  from 
the  organ,  or  by  a  very  simple  method  introduced  by  Brodie ;  the 
organ  is  enclosed  in  an  oncometer  connected  to  a  bellows  recorder ;  the 
issuing  vein  is  compressed  for  about  a  second,  and  the  blood  flowing 
into  the  organ  causes  it  to  expand;  the  lever  of  the  recorder  rises 
quickly  or  slowly  according  to  the  rate  at  which  the  blood  is  flowing 
into  the  organ.  The  recorder  is  first  calibrated  by  injecting  half  a 
cubic  centimetre  of  water  into  the  tubing  leading  to  it,  and  the 
position  of  the  lever  at  rest,  and  that  which  it  occupies  when  the 
oncometer  is  distended  by  half  a  cubic  centimetre  of  water  are 
marked  continuously  by  two  fixed  writing-points.  In  the  accom- 
panying figure,  obtained  from  an  experiment  on  a  kidney,  these  two 
lines  are  lettered  A  and  B.  The  surface  travels  at  a  quick  rate,  and 
the  time-tracing  T  shows  thirtieths  of  a  second.  The  line  C  is  traced 
by  the  oncometer  lever. 


GIL  XXV II.] 


TISSUE  RESPIRATION 


397 


At  the  point  D  the  renal  vein  was  compressed,  and  at  the  point 
E  the  compression  ceased.  From  D  to  E  the  inflowing  blood  caused 
the  kidney  to  expand  and  the  recording  lever  to  rise.  It  crosses  the 
two  horizontal  lines  at  F  and  G  respectively.  During  this  time 
(F  to  G),  therefore,  half  a  cubic  centimetre  of  blood  entered  the 
kidney,  and  this  time  was  thirty-three  vibrations  of  the  time-marker, 
that  is  1-1  second.  Hence  the  rate  of  blood-flow  would  be 

— :p: =  27-3  c.c.  of  blood  per  minute. 

In  order  to  measure  the  gaseous  exchange  of  an  organ  over  a 
long  period  the  organ  is  supplied  with  blood  which  alternately 
traverses  the  organ  and  aerates  itself  in  a  closed  chamber.  The 
amount  of  oxygen  in  the  chamber  is  kept  constant  by  the  addition  of 
that  gas  to  the  air  of  the  chamber  at  the  same  rate  at  which  the 
circulation  acquires  it.  The  amount  of  oxygen  so  added  is  measured. 
The  method  has  recently  been  applied  with  conspicuous  success  to 
the  gaseous  exchange  of  the  heart. 

Relation  of  Tissue  Respiration  to  Functional  Activity. 

In  all  organs,  so  far  as  is  known,  increased  activity  is  accom- 
panied by  increased  oxidation. 

Much  interest  centres  about  the  question  of  the  order  of  time 
in  which  these  events  take  place.  This  matter  has  been  investigated 


FIG. 


minutes 


. — Tiie  black-white  line  represents  rate  of  salivary  secretion  in  c.c.  per  minute.    S — S= 
line  for  saliva.    Black  area  =  oxygen  used  by  the  gland.     0— 0= oxygen  base  line. 


in  the  case  of  skeletal  muscle  and  the  submaxillary  gland  (fig.  309), 
both  of  which  organs  can  be  thrown  into  profound  activity  for  a  short 
space  of  time ;  in  each  case  most  of  the  oxidation  follows  upon  the 
activity,  and  not  the  activity  upon  the  oxidation.  The  important 
inference  is  drawn  that  the  contraction  or  secretion,  as  the  case  may 
be,  is  not  caused  by  the  oxidation  in  the  sense  that  the  machinery  of  a 
locomotive  is  driven  by  the  energy  derived  from  the  oxidation  of  the 
coal ;  rather  is  the  mechanism  like  that  of  a  spring  which  is 
liberated  at  the  moment  of  doing  the  work,  and  has  to  be  rewound 
subsequently ;  the  process  of  rewinding  involves  oxidation.  In  the 
case  of  muscle,  the  heat-formation  which  occurs  in  the  period 


398 


RELATION   OF   RESPIRATION   TO   OTHER   PROCESSES     [CH.  XXVII. 


following  activity  only  takes  place  if  the  muscle  is  supplied  with 
oxygen.  The  output  of  carbonic  acid,  in  its  turn,  follows  upon  the 
intake  of  oxygen.  The  order  of  events  is  therefore  (1)  increase  of 
functional  activity,  (2)  increase  of  heat  formation  and  oxygen  taken 
in,  and  (3)  increase  of  carbonic  acid  put  out. 

The  following  table  shows  the  coefficients  of  oxidation  for  resting 
organs,  and  the  extent  to  which  they  are  increased  in  activity. 


Organ. 

Condition  of  Rest. 

Oxygen  used 
per  minute 
per  gramme 
of  organ. 

Condition  of 
Activity. 

Oxygen  used 
per  minute 
per  gramme 
of  organ. 

Voluntary 
muscle. 

Nerves  cut. 
Tone  absent. 

0-003  C.c. 

Tone  existing  in  rest. 
Gentle  contraction. 
Active  contraction. 

0*006  C.C. 
0'020  c.c. 
0-080  c.c. 

Unstriped 
muscle. 

Resting 

0-004  c.c. 

Contracting. 

0*007  c.c. 

Heart 

Very  slow  and 
feeble      con- 
tractions. 

0-007  c.c. 

Normal  contractions. 
Very  active. 

0-05  c.c. 
0'08  c.c. 

Submaxillary 
gland. 

Nerves  cut. 

0-03  c.c. 

Chorda  stimulation. 

O'lO  c.c. 

Pancreas. 

Not  secreting. 

0-03  c.c. 

Secretion  after  injection 
of  sec»etin. 

0-10  c.c. 

Kidney. 

Scanty  secretion. 

0-03  c.c. 

After     injection    of 
diuretic. 

0-10  c.c. 

Intestines. 

Not  absorbing. 

0-02  c.c. 

Absorbing  peptone. 

0-03  c.c. 

Liver. 

In       fasting 
animal. 

0-01  to 
0'02  c.c. 

In  fed  animal. 

0-03  to 
0-05  c.c. 

Suprarenal 
gland. 

Normal. 

•045  c.c. 

... 

... 

In  many  cases  the  quantitative  relationships  have  not  been 
worked  out. 

Eecent  research  has  shown  that  in  the  case  of  the  heart,  if  N  is 
the  number  of  beats  per  minute,  T,  the  maximum  blood -pressure 
which  is  attained  at  each  beat,  and  0,  the  amount  of  oxygen  used : 

NxT 

then  — —  is  a  constant  quantity,  unless  the  cardiac  muscle  is  itself 


CH.  XXVII.]  OXYGEN  WANT  399 

rendered  less  efficient,  as  may  be  done  by  the  use  of  drugs.  This  is 
in  agreement  with  a  series  of  researches  on  the  heat  given  out  by 
frogs'  muscle,  which  shows  that  the  heat  given  out  in  a  single 
contraction  varies  directly  with  the  tension  in  the  muscle.  The 
efficiency  of  the  heart  regarded  as  a  machine  seems  to  be  low  (about 
2  per  cent.),  owing  perhaps  to  the  anatomical  disposition  of  the  strands 
of  fibres. 

Intensity  of  Respiration. — Most  of  the  figures,  relating  to  gaseous 
metabolism  given  in  the  preceding  paragraphs  were  obtained  from 
the  examination  of  the  tissues  and  organs  of  the  dog.  If  all  the 
tissues  were  examined  in  turn,  and  their  relative  weights  known, 
an  average  might  be  struck  which  would  give  the  gaseous  met- 
abolism for  the  body  taken  as  a  whole,  and  this  might  be  expressed 
as  the  amount  of  oxygen  used  per  minute  per  gramme  of  body- 
weight.  An  easier  and  more  practicable  method,  however,  is  to  weigh 
the  animal,  and  then  from  the  composition  of  the  inspired  and 
expired  air  and  the  amount  of  oxygen  taken  in  and  given  out, 
calculate  how  much  is  retained  and  utilised.  In  the  dog,  the 
amount  is  about  0-016  c.c.  of  oxygen  per  minute  per  gramme  of 
body-weight.  This  figure,  however,  is  not  the  same  in  all  animals, 
and  the  size  of  the  figure  will  indicate  what  we  may  term  the 
intensity  of  respiration.  Thus  in  cold-blooded  animals,  especially 
fishes  with  their  small  supply  of  oxygen,  the  figure  is  very  much 
smaller.  Among  warm-blooded  animals  great  variations  are  also 
seen ;  the  intensity  of  respiration,  for  instance,  is  much  greater  in 
birds  than  in  mammals.  Among  the  mammals,  the  intensity  of 
respiration  varies,  roughly,  inversely  with  the  size  of  the  animal  ; 
thus,  in  the  mouse,  an  animal  that  breathes  with  extreme  rapidity, 
the  intensity  is  probably  ten  to  fifteen  times  greater  than  in  the 
dog,  and  in  the  elephant  very  much  less.  In  man,  the  average  is 
about  half  that  in  the  dog,  that  is,  0-008  c.c.  of  oxygen  per 
gramme  of  body-weight  per  minute. 

Oxygen  Want. 

The  balance  between  the  demand  for  oxygen  and  the  supply 
may  be  upset  either  by  increasing  the  demand  or  decreasing  the 
supply. 

Oxygen  want  may  therefore  take  place  either  as  the  result  of 
violent  exercise  or  of  diminished  oxygen  pressure.  Normally  a  man 
takes  into  his  blood  about  400  c.c.  of  oxygen  per  minute,  in  sleep 
about  half  this,  and  in  such  exercise  as  is  afforded  by  the  pushing  of 
a  motor  bicycle  up  a  steep  hill,  3000  c.c.  per  minute  or  more  are 
absorbed  by  the  blood.  During  the  violent  contraction  of  a  muscle, 
the  blood-now  through  it  is  momentarily  retarded,  though  over  a 
considerable  interval  of  time  it  is  much  increased.  Nevertheless 


400  KELATION   OF  RESPIRATION   TO   OTHER   PROCESSES     [CH.  XXVII. 

the  momentary  retardation  leads  to  a  certain  amount  of  oxygen 
want,  and  this  is  probably  the  cause  of  the  lactic  acid  output,  to 
which  we  have  drawn  attention  (see  pp.  381  and  395).  Lactic  acid 
production  in  muscle  indicates  incomplete  oxidation.  The  acid 
itself  probably  increases  the  blood -supply  to  the  muscle  automati- 
cally by  relaxing  the  arteriole  walls. 

The  symptoms  produced  by  exercise  and  by  decreased  pressure 
(as  in  mountain  sickness)  are  not  the  same,  probably  because .  the 
former  is  accompanied  by  an  increase  in  the  production  of  carbonic 
acid  and  of  heat.  Indeed  most  of  the  symptoms  which  are  the 
ordinary  effects  of  exercise  are  due  probably  to  these  causes,  the 
actual  oxygen  supply  to  the  brain  being  adequate  during  exercise. 

Mountain  Sickness. 

The  symptoms  of  mountain  sickness  differ  in  different  persons 
as  do  those  of  other  forms  of  intoxication.  In  one  person  vomiting 
will  be  the  prominent  feature,  in  another,  absence  of  self-restraint, 
in  a  third,  inability  to  perform  any  task,  such  as  arithmetic,  involving 
accurate  cerebral  processes.  There  is  no  doubt  that  the  cause  is 
want  of  oxygen.  This  lack  of  oxygen  causes  the  production  of  the 
poisonous  materials,  which  affect  the  brain  and  produce  the  symptoms. 
These  toxic  substances  are  no  doubt  products  of  incomplete  oxidation ; 
it  is  not  clear  how  far  these  are  produced  in  the  brain,  and  how  far 
they  are  carried  to  it  in  the  blood. 

In  considering  what  is  the  lowest  pressure  of  oxygen  consistent 
with  normal  function,  it  must  be  borne  in  mind  that  with  lungs  of  a 
given  size  this  limiting  pressure  varies  directly  with  the  number  of 
c.c.  of  oxygen  which  must  be  absorbed  (Bohr). 

The  effect  of  exercise  is  to  increase  the  amount  of  oxygen 
required  by  the  tissues.  The  amount  of  oxygen  required  by  the 
same  person  under  different  circumstances  varies  very  much.  Thus 
Zuntz  resting  and  fasting  on  Monte  Eosa  required  only  259  c.c.  of 
oxygen  per  minute,  whilst  in  the  act  of  climbing  he  wanted  1329  c.c. 
of  oxygen  per  minute. 

In  the  former  condition  he  could  have  remained  in  comfort  at  an 
altitude  at  which  the  pressure  of  oxygen  in  his  alveoli  was  very  low, 
but  as  soon  as  he  made  any  effort  he  realised  that  this  pressure  of 
oxygen  was  insufficient  to  allow  him  to  do  muscular  work. 

Now  the  alveolar  pressure  depends  partly  on  the  barometric 
pressure,  and  partly  on  the  nature  of  the  respiration.  The  deeper 
the  respiration  the  more  nearly  does  the  pressure  of  oxygen  in  the 
alveoli  approximate  to  that  in  the  atmosphere  (i.e.  the  higher  is  the 
alveolar  pressure  of  oxygen).  Thus  it  happens  that  men  who  take 
deep  respirations  can  tolerate  altitudes  which  are  impossible  for 


CH.  XXVII.]  MOUNTAIN   SICKNESS  401 

shallow    breathers.      This   is   illustrated   by   the   following    figures 
obtained  from  observations  on  three  different  men : — 


c.c.  of  air 
per 
inspiration. 
270 
440 
700 

Number  of 
respirations 
per  minute. 
20 
14 
8 

Height  in  metres 
at  which  distress 
was  felt. 
3300 
6000 
6500 

Subject  1 
„  2 
„  3  . 

Mountain  sickness  therefore  attacks  different  persons  at  different 
altitudes.  If  no  form  of  adaptation  took  place,  the  following  would 
be  the  approximate  pressures  of  oxygen  in  the  pulmonary  alveoli  at 
the  following  altitudes : — 

Sea  level        .  .     100  mm. 

10,000  feet     .  .       59  mm. 

15,000  feet    .  .       38  mm. 

It  is  known  lhat  at  alveolar  pressures  of  60  mm.  or  thereabouts 
the  symptoms  of  oxygen  want  begin  in  an  artificial  chamber.  Inspec- 
tion of  the  dissociation  curve  of  human  blood,  p.  370,  will  show 
that  at  59  mm.  the  arterial  blood  might  be  upwards  of  85  per  cent, 
saturated  with  oxygen,  but  at  38  mm.  it  would  be  only  66  per  cent, 
saturated.  This  condition  of  the  blood  would  account  for  the 
symptoms. 

Methods  of  adaptation  to  high  altitudes.  —  Apart  from  the 
question  of  "  training "  which  will  be  dealt  with  below,  adaptation 
takes  place  along  two  lines,  each  of  which  tends  to  bring  more 
oxygen  into  a  given  quantity  of  blood.  This  is  accomplished  (1)  by 
raising  the  alveolar  pressure  of  oxygen  higher  than  the  figures  given 
above ;  and  (2)  by  increasing  the  quantity  of  haemoglobin  in  the  blood. 

The  rise  in  alveolar  oxygen  pressure  is  brought  about  by  more 
rapid  breathing.  The  more  rapid  breathing  in  turn  is  the  result  of 
the  respiratory  centre  being  hustled  by  acid  formation  if  the  respira- 
tion slows  down.  There  is  therefore  more  oxygen  and  less  carbonic 
acid  in  the  alveolar  air  and  in  the  blood  than  there  otherwise  would 
be.  Actually,  the  oxygen  pressures  in  the  alveolar  air  were  found 
to  be: — 

Sea  level        .  .100  mm. 

10,000  feet    .  .       65  mm. 

15,000  feet     .  .       52  mm. 

The  chief  difference  is  naturally  at  the  greatest  altitude.  Here, 
instead  of  the  alveolar  oxygen  pressure  being  38  mm.  it  is  52  mm. ; 
the  blood  could  therefore  become  about  80  per  cent,  instead  of  66  per 
cent.,  saturated  with  oxygen — a  very  material  increase.  Moreover, 
since  the  rate  at  which  the  blood  becomes  oxygenated  is  directly 
proportional  to  the  oxygen  pressure,  the  difference  between  38  mm. 
and  52  mm.  is  most  beneficial.  The  figures  for  the  percentage 

2    C 


402  RELATION   OF   RESPIRATION   TO   OTHER   PROCESSES     [CH.  XXVII. 

saturation  are  obtained  by  employing  the  dissociation  curve  for  blood 
at  40  mm.  carbonic  acid  pressure.  The  legitimacy  of  this  may  be 
questioned,  since  the  carbonic  acid  pressure  in  the  blood  at  an  eleva- 
tion of- 15,000  feet  is  only  about  25  mm.*  The  curve  is,  however, 
true  for  the  blood  at  all  altitudes  since  the  reaction  of  the  blood 
remains  the  same  (or  may  shift  a  trifling  amount  to  the  acid  side), 
some  other  less  volatile  acid  making  up  for  the  deficiency  in  carbonic 
acid. 

Increase  of  haemoglobin  in  the  blood. — At  high  altitudes  the 
number  of  corpuscles  per  cubic  millimetre  in  human  blood  is  said  to 
be  excessive.  Some  caution  is  necessary  in  attributing  physiological 
significance  to  such  statements,  for  they  may  be  in  part  illusory.  In 
balloon  ascents,  for  instance,  the  number  of  corpuscles  in  blood  may 
increase  very  rapidly.  This  is  not  due  to  fresh  formation  of  blood, 
but  to  the  excessive  secretion  of  lymph,  which  leads  to  concentration 
of  the  blood.  Nevertheless,  in  animals  kept  at  high  altitudes  for 
some  days  there  is  an  actual  increase  in  the  formation  of  corpuscles, 
as  shown  by  the  appearance  of  nucleated  corpuscles  thrust  into  the 
blood  by  the  bone-marrow,  and  an  increase  in  the  amount  of  iron  in 
the  blood  at  the  expense  of  the  quantity  of  that  element  in  the  liver. 

Training.  —  We  have  seen  that  a  factor  in  the  onset  of 
mountain  sickness  is  the  amount  of  oxygen  which  passes  through 
the  lung  epithelium.  It  is  a  matter  of  experience  that  from 
various  causes  an  individual  can  do  the  same  amount  of  muscular 
work,  such  as  performing  the  same  mountain-climb,  with  a  less 
degree  of  metabolism  after  training.  This  is  in  part  due  to  the  fact 
that  the  trained  person  has  lost  unnecessary  weight,  and  in  part 
because  he  uses  his  muscles  to  better  advantage.  Thus  every  unit  of 
energy  spent  in  work  demanded  a  total  expenditure  of  energy  of  7 
units  in  the  case  of  an  untrained  town-dweller,  5  units  in  the  case 
of  a  partially  trained  tourist,  and  3-3  units  in  the  case  of  an  Alpine 
porter.  Therefore,  in  the  same  climb,  the  Alpine  carrier  would  only 
suffer  half  the  increase  of  metabolism  that  the  town-dweller  would. 
He  would  therefore  need  correspondingly  less  oxygen,  and  he  could 
reach  a  height  at  which  he  would  have  a  correspondingly  lower 
alveolar  oxygen  tension. 

Respiration  at  High  Pressures. 

Prolonged  exposure  to  pressures  of  oxygen,  equal  to  1300  to  1400 
mm.  of  mercury,  induces  pneumonia,  and  death  rapidly  follows.  It  is 

*  The  diminution  of  carbonic  acid  tension  in  alveolar  air  and  blood  is  termed 
acapnia,  and  Thorso  attributed  mountain  sickness  to  this  condition.  Although 
this  view  is  incorrect,  it  is  necessary  to  remember  that  carbonic  acid  is  not  a  mere 
waste  product,  but  performs  certain  duties  in  the  body  (stimulating  respiration 
and  assisting  the  dissociation  of  oxy haemoglobin);  in  certain  conditions,  as  in 
shock,  acapnia  is  an  important  factor. 


GIL  XXVII.]  CARBON   MONOXIDE  POISONING  403 

not  possible,  therefore,  for  men  to  work  in  air  which  is  compressed 
to  the  extent  of  producing  so  great  a  pressure  of  oxygen. 

Caisson  disease. — In  the  boring  of  tunnels  and  in  carrying  out 
operations  in  the  beds  of  rivers,  it  is  usual  to  sink  an  iron  tube  in 
which  the  men  work.  This  tube  or  caisson  is  closed  except  at  the 
end  at  which  the  work  is  progressing,  and  the  water  is  prevented 
from  inundating  it  by  pumping  air  into  it  at  a  pressure  higher 
than  that  of  the  water.  The  men  enter  through  a  chamber  with 
double  doors  or  "air-lock."  In  this  chamber  the  pressure  can  be 
raised  or  lowered.  The  pressure  in  the  caisson  rarely  exceeds 
4  atmospheres,  which  corresponds  to  about  600  mm.  of  oxygen; 
at  this  pressure  the  workers  do  not  suffer  whilst  they  are  in  the 
caisson,  but  grave  symptoms  may  take  place  shortly  after  they  have 
come  out.  Similar  symptoms  are  experienced  by  divers  who  come  to 
the  surface  from  great  depths.  The  symptoms  may  take  the  form  of 
paralysis,  vomiting,  severe  abdominal  pain,  vertigo,  etc.  They  are  due 
to  the  fact  that  the  plasma,  and  indeed  all  the  fluids  which  permeate 
the  organs  of  the  body,  become  saturated  with  oxygen  and  nitrogen 
at  the  pressure  of  the  caisson,  and  therefore  when  the  pressure 
is  suddenly  removed,  minute  bubbles  form  throughout  the  body 
and  injure  such  tissues  as  the  spinal  cord,  or  produce  blockage 
of  the  vessels.  Short  hours  are  necessary  for  caisson  workers,  for 
then  the  body  has  not  time  to  get  saturated  with  air  at  the  caisson 
pressure,  and  in  all  cases  "decompression"  must  be  gradual  and 
slow;  this  gradual  release  from  pressure  is  accomplished  in  the 
"  air-lock."  The  dangers  we  have  mentioned  then  cease  to  exist. 

The  atmospheric  gases  are  specially  soluble  in  fat;  fat  people 
are  therefore  very  susceptible  to  caisson  disease,  and  should,  in  fact, 
be  prohibited  from  labour  in  caissons. 

Carbon  Monoxide  Poisoning. 

The  fatal  effects  often  produced  by  this  gas  (as  in  accidents  from 
burning  charcoal  stoves  in  small  close  rooms,  or  where  there  is  an 
escape  of  coal  gas),  are  due  to  its  entering  into  combination  with  the 
haemoglobin  of  the  blood-corpuscles,  and  thus  hindering  their  oxygen- 
carrying  function.  In  an  atmosphere  containing  both  oxygen  and 
carbon  monoxide,  the  relative  quantities  of  the  two  gases  which  the 
haemoglobin  will  absorb  varies  with  the  partial  pressure  of  the 
gases.  The  affinity  of  haemoglobin  for  carbon  monoxide  is,  how- 
ever, much  greater  than  its  affinity  for  oxygen,  and  the  compound 
formed — carboxyhaemoglobin — is  much  more  stable  than  oxy haemo- 
globin is.  If,  therefore,  any  considerable  quantity  of  carbon  mon- 
oxide is  present  in  the  air,  the  haemoglobin  will  be  almost  completely 
charged  with  carboxyhaemoglobin,  and  asphyxia  would  follow.  If 
the  patient  is  given  pure  oxygen  to  breathe  even  at  a  late  stage, 


404  RELATION   OF   RESPIRATION   TO   OTHER   PROCESSES     [CH.  XXVII. 

two  things  will  happen:— (1)  The  blood  will  take  up  in  simple 
physical  solution  about  seven  times  as  much  oxygen  as  when  exposed 
to  air,  and  this  may  be  sufficient  to  carry  on  life ;  (2)  as  regards  the 
saturation  of  the  haemoglobin,  the  balance  is  now  in  favour  of  the 
oxygen,  weak  as  its  affinity  for  haemoglobin  is,  and  the  carbon 
monoxide  gradually  works  its  way  out  of  the  body. 

Cheyne-Stokes  Respiration. 

This  is  a  condition  in  which  the  breathing  waxes  and  wanes  to  a 
remarkable  degree  (fig.  310).  It  is  an  exaggeration  of  the  type  of 
respiration  which  is  often  seen  during  sleep  in  perfectly  healthy 
people.  The  condition  was  first  observed  by  the  two  Dublin 
physicians  whose  names  it  bears.  It  may  be  induced  in  normal 
persons  if  they  make  themselves  pant  violently  for  1-2  minutes. 
If  then  respiration  is  allowed  to  take  its  own  course,  there  will  first 


FIG.  310. — Stethograph  tracing  of  Cheyne-Stokes  respiration  in  a  man.    The  time  is 
marked  in  seconds.  (Pembrey  and  Allen.) 

be  a  pause  (apnoea),  then  Cheyne-Stokes  respiration  will  be  set  up. 
The  groups  will  become  less  and  less  distinct,  and  respiration  will 
ultimately  become  normal.  The  explanation  of  this  phenomenon 
is  as  follows : — 

The  panting  causes  an  undue  amount  of  carbonic  acid  to  leave 
the  body,  with  the  result  that  the  carbonic  acid  tension  in  the  blood 
and  in  the  tissues  sinks  to  perhaps  a  quarter  or  a  third  of  its  usual 
value.  Already  we  have  seen  that  carbonic  acid  is  an  active  stimulant 
to  the  respiratory  centre,  and  its  removal  causes  respiration  to  cease, 
hence  the  apnoea.  But  during  the  apnoeic  period  the  arterial  blood 
becomes  less  and  less  oxygenated,  with  the  result  that  lactic  acid 
formation  (a  constant  result  of  oxygen  want)  takes  place  in  the  tissues  ; 
the  lactic  acid,  like  carbonic  acid,  stimulates  the  respiratory  centre, 
which  remains  active  till  the  advent  of  oxygen  causes  oxidation  of 
the  acid;  there  is  then  another  pause,  and  so  on.  Cheyne-Stokes 
breathing  is  dependent,  then,  on  oxygen  want. 


CH.  XXVII.]  DIABETIC    COMA  405 

"  If  from  any  cause,  such  as  cerebral  haemorrhage  or  circulatory 
failure,  the  circulation  through  the  respiratory  centre  is  interfered 
with,  or  if  the  absorption  of  oxygen  is  interfered  with  by  such  causes 
as  diminished  barometric  pressure  or  pathological  conditions  in 
the  lungs,  the  occurrence  of  periodic  or  Cheyne-Stokes  breathing 
becomes  easily  intelligible." — (Haldane  and  Douglas). 

Pathological  Cheyne-Stokes  respiration  may  be  removed  by 
administration  either  of  oxygen  or  of  carbonic  acid. 

Pembrey  and  Pitts  have  also  taken  tracings  of  the  same  condition 
in  the  hibernating  dormouse,  hedgehog,  marmot,  and  bat.  In  some 
cases  the  respiration  has  the  typical  Cheyne-Stokes  character,  with  a 
gradual  waxing  and  waning.  In  other  cases  periods  of  respiratory 
activity  alternate  with  periods  of  apnoea,  but  all  the  respiratory 
efforts  are  about  equal  in  force.  This  is  known  as  Biot's  respiration, 


FIG.  311. — Biot's  respiration  in  hibernating  dormouse.  The  line  marked  T  gives  time  in  seconds. 
Line  1  gives  the  tracing  of  a  respiratory  group  which  occurred  once  every  SO  seconds,  the  tempera- 
ture of  the  animal  being  11°  C.  On  warming  the  animal  to  13°  C.  the  respiratory  groups  became 
more  frequent  (line  2).  On  warming  the  animal  still  further  it  awakened,  and  breathing,  at  first 
accompanied  by  shivering,  became  continuous.  (Pembrey  and  Pitts.) 

and  is  illustrated  by  the  accompanying   illustration  taken  from  a 
hibernating  dormouse. 

Diabetic  Coma. 

In  the  preceding  chapter  conditions  have  been  considered  which 
depend  upon  the  stimulus  given  to  the  respiratory  centre  by  the  con- 
dition of  the  gases  in  the  blood.  Carbonic  acid  is,  however,  not 
the  only  body  capable  of  affecting  the  respiratory  centre;  lactic 
acid,  as  we  have  just  seen,  will  stimulate  it,  and  probably  all  other 
acids  in  solution  will  do  the  same.  If,  therefore,  other  acid  radicals 
are  thrown  into  the  blood,  the  respiration  will  increase  till  the 
amount  of  carbonic  acid  in  the  blood  is  proportionally  decreased. 
It  is  the  total  concentration  of  such  radicals,  or  rather  of  the 
hydrogen  ions  which  they  carry  in  their  wake,  that  remains  a 
constant  factor.  In  diabetic  coma  other  acids  (e.g.,  hydroxybutyric) 
make  their  appearance,  and  the  respiration  is  exaggerated  till  only 
a  small  amount  of  carbonic  acid  remains. 


CHAPTEE  XXVIII 

THE  CHEMICAL  COMPOSITION  OF  THE  BODY 

THE  elements  found  in  the  body  are  carbon,  nitrogen,  hydrogen, 
oxygen,  sulphur,  phosphorus,  fluorine,  chlorine,  iodine,  silicon,  sodium, 
potassium,  calcium,  magnesium,  lithium,  iron,  and  occasionally  traces 
of  manganese,  copper,  and  lead. 

Of  these,  very  few  occur  in  the  free  state.  Oxygen  (to  a  small 
extent)  and  nitrogen  are  found  dissolved  in  the  blood ;  hydrogen  is 
formed  by  putrefaction  in  the  alimentary  canal.  With  some  few 
exceptions  such  as  these,  the  elements  enumerated  above  are  found 
combined  with  one  another  to  form  compounds. 

The  compounds,  or,  as  they  are  frequently  termed  in  physiology, 
the  proximate  principles,  found  in  the  body  are  divided  into — 

(1)  Mineral  or  inorganic  compounds. 

(2)  Organic  compounds,  or  compounds  of  carbon. 

The  inorganic  compounds  present  are  water,  various  acids  (such 
as  hydrochloric  acid  in  the  gastric  juice),  ammonia  (as  in  the  urine), 
and  numerous  salts,  such  as  calcium  phosphate  in  bone,  sodium  chloride 
in  blood  and  urine,  and  many  others. 

The  organic  compounds  are  more  numerous ;  they  may  be  sub- 
divided into — 

(Proteins— e.g.,  albumin,  myosin,  casein,  gelatin,  etc. 
Nitrogenous          -|  Simpler  nitrogenous  bodies — e.g.,  lecithin,  urea, 
[     creatine. 
[Fats — e.g.,  butter,  fats  of  adipose  tissue. 

Non  nifrna-^nmiQ     Carbohydrates— e.g.,  sugar,  starch. 
Non-nitrogenous  ->  a-    „/*  „.     „.,.•,.  iJL*~ 


\  Simpler  organic  bodies — e.g.,  cholesterin,  lactic 


acid. 


The  subdivision  of  the  organic  proximate  principles  into  proteins, 
fats,  and  carbohydrates  forms  the  starting-point  of  chemical  physiology. 

Carbohydrates. 

The  Carbohydrates  are  found  chiefly  in  vegetable  tissues,  and 
many  of  them  form  important  foods.  Some  carbohydrates  are,  how- 
ever, found  in  or  formed  by  the  animal  organism.  The  most  important 

406 


CH.  XXVIII.]  THE   CARBOIIYDEATKS  407 

of  these  are  glycogen,  or  animal  starch ;  dextrose ;  and  lactose,  or  milk 
sugar. 

The  carbohydrates  may  be  conveniently  defined  as  compounds  of 
carbon,  hydrogen,  and  oxygen,  the  two  last-named  elements  being  in 
the  proportion  in  which  they  occur  in  water.  But  this  definition  is 
only  a  rough  one,  and  if  pushed  too  far  would  include  many  substances 
such  as  acetic  acid,  lactic  acid,  and  inosite,  which  are  not  carbohydrates. 
Kesearch  has  shown  that  the  chemical  constitution  of  the  simplest 
carbohydrates  is  that  of  an  aldehyde,  or  a  ketone,  and  that  the  more 
complex  carbohydrates  are  condensation  products  of  the  simple  ones. 
In  order,  therefore,  that  we  may  understand  the  constitution  of  these 
substances,  it  is  first  necessary  that  we  should  understand  what  is 
meant  by  the  terms  aldehyde  and  ketone. 

A  primary  alcohol  is  one  in  which  the  hydroxyl  (OH)  and  two 
hydrogen  atoms  are  attached  to  the  same  carbon  atom ;  it,  therefore, 
contains  the  group  CH2OFI.  Thus  the  formula  for  common  alcohol 
(primary  ethyl  alcohol)  is 

CH3.CH2OH. 

The  formula  for  the  next  alcohol  of  the  same  series  (primary 
propyl  alcohol)  is 

CH3.CH2.CH2OH. 

If  a  primary  alcohol  is  oxidised,  the  first  oxidation  product  is 
called  an  aldehyde  ;  thus  ethyl  alcohol  yields  acetic  aldehyde : — 
CH3.CH9OH    +   O   =   CH3.COH    +   H2O. 

[Ethyl  alcohol.]  [Acetic  aldehyde.] 

The  typical  group  COH  of  the  aldehyde  is  not  stable,  but  is  easily 
oxidisable  to  form  the  group  COOH  (carboxyl),  and  the  compound  so 
formed  is  called  an  acid ;  in  this  way  acetic  aldehyde  forms  acetic 
acid : — 

CH3.COH    +   O   =   CH3.COOH. 

[ Acetic  aldehyde. ]  [Acetic  acid. ] 

The  majority  of  the  simple  sugars  are  aldehydes  of  more  complex 
alcohols  than  this ;  they  are  spoken  of  as  aldoses.  The  readiness  with 
which  aldehydes  are  oxidisable  renders  them  powerful  reducing  agents, 
and  this  furnishes  us  with  some  of  the  tests  for  the  sugars. 

Let  us  now  turn  to  the  case  of  the  ketones.  A  secondary  alcohol  is 
one  in  which  the  OH  group  and  one  hydrogen  atom  are  attached  to  the 
same  carbon  atom ;  thus  secondary  propyl  alcohol  has  the  formula 

CH3.CHOH.CH3. 

Its  typical  group  is  therefore  CHOH.     When   this  is  oxidised,  the 
first  oxidation  product  is  called  a  ketone,  thus : — 

CH3.CHOH.CH3   +    O    =    CH3.CO.CH3   +    H2O. 

[Secondary  propyl  alcohol.]  [Propyl  ketone  or  acetone.] 

It  therefore  contains  the  group  CO. 

Some  of  the  sugars  are  ketones  of  more  complex  alcohols ;  these 


408  THE   CHEMICAL   COMPOSITION   OF  THE   BODY      [CH.  XXVIII. 

are  called  Jcetoses.  The  only  one  of  these  which  is  of  physiological 
interest  is  laevulose. 

The  alcohols  of  which  we  have  already  spoken  are  called  monatomic, 
because  they  contain  only  one  OH  group.  Those  which  contain  two 
OH  groups  (such  as  glycol)  are  called  diatomic ;  those  which  contain 
three  OH  groups  (such  as  glycerin)  are  called  triatomic ;  and  so  on. 
The  hexatomic  alcohols  are  those  which  contain  six  OH  groups.  Three 
of  these  hexatomic  alcohols  with  the  formula  C6H8  (OH)6  are  of 
physiological  interest ;  they  are  isomerides,  and  their  names  are  sorbite, 
mannite,  and  dulcite.  By  careful  oxidation  their  aldehydes  and 
ketones  can  be  obtained ;  these  are  the  simple  sugars ;  thus,  dextrose 
is  the  aldehyde  of  sorbite;  mannose  is  the  aldehyde  of  mannite; 
laevulose  is  the  ketone  of  mannite ;  and  galactose  is  the  aldehyde  of 
dulcite.  These  sugars  all  have  the  empirical  formula  C6H1206.  They 
furnish  an  excellent  example  of  what  is  called  stereochemical 
isomerism ;  that  is,  the  position  of  the  atoms  or  groups  of  atoms  in 
space  within  the  sugar  molecule  varies.  The  constitutional  formulae 
of  three  important  simple  sugars  are  shown  below.  The  six  carbon 
atoms  in  each  case  form  an  open  chain,  but  the  way  in  which  the 
hydrogen  and  hydroxyl  atoms  are  linked  to  them  differs. 

CH2OH  CH2OH  CH2OH 

H— C— OH  H— C— OH  H— C— OH 

H—C— OH  H— C— OH  OH— C— H 

I  1  i 

OH— C— H  OH— C— H  OH— C— H 

H—C— OH  C-O  H—C— OH 

I  I  I 

C— OH  CH2OH  C— OH 

[Dextrose.]  [Laevulose.]  [Galactose.] 

The  aldehyde  constitution  of  dextrose  and  galactose  is  at  once 
evident,  the  typical  aldehyde  group  (COH)  being  at  the  end  of  the 
chain,  whereas  the  ketone  constitution  of  laevulose  is  shown  by  the 
typical  ketone  group  (CO)  not  at  the  end  of  the  chain. 

By  further  oxidation,  the  sugars  yield  acids  with  various  names. 

If  we  take  such  sugars  as  typical  specimens,  we  see  that  their 
general  formula  is 

CnH2mOm 

and  as  a  general  rule  n  =  m ;  that  is,  the  number  of  oxygen  and  carbon 
atoms  are  equal.  This  number  in  the  case  of  the  sugars  already 
mentioned  is  six.  Hence  they  are  called  hexoses. 

Sugars  are  known  to  chemists,  in  which  this  number  is  3,  4,  5,  7,  etc.,  and 
these  are  called  trioses,  tetroses,  pentoses,  heptoses,  etc.  The  majority  of  these 


CH.  XXVIII.]  THE   CARBOHYDRATES  409 

have  no  physiological  interest.  It  should,  however,  be  mentioned  that  a  pentose 
has  been  obtained  from  the  certain  nucleic  acids  presently  to  be  described  (see  p. 
431)  which  are  contained  in  animal  organs  (pancreas,  liver,  etc.),  and  in  plants 
(for  instance,  yeast).  If  the  pentoses  which  are  found  in  various  plants  are  given 
to  an  animal,  they  are  excreted  in  great  measure  unchanged  in  the  urine. 

The  hexoses  are  of  great  physiological  importance.  The  principal 
ones  are  dextrose,  laevulose,  and  galactose.  These  are  called  mono- 
saccharides. 

Another  important  group  of  sugars  are  called  disaccharides  ; 
these  are  formed  by  what  is  called  condensation ;  that  is,  two  mole- 
cules of  monosaccharide  combine  together  with  the  loss  of  a  molecule 
of  water,  thus : — 

C6H1206   +   C6H1206   ==   C12H22On   +    H20. 

The  principal  members  of  the  disaccharide  group  are  cane  sugar, 
lactose,  and  maltose. 

If  more  than  two  molecules  of  the  monosaccharide  group  undergo 
a  corresponding  condensation,  we  get  what  are  called  polysaccharides. 

nC6H1206   =   (C6H1005)n   +   "H20. 

The  principal  polysaccharides  are  starch,  glycogen,  various  dextrins, 
and  cellulose.  We  may,  therefore,  arrange  the  important  carbo- 
hydrates of  the  hexose  family  in  a  tabular  form  as  follows : — 


1.  Monosaccharides, 
C6H1206, 

2.  Disaccharides, 
OxtHj.Oj,. 

3.  Polysaccharides 
(C6H1006)« 

+  Dextrose. 
-  Laevulose. 
+  Galactose. 

+  Cane  sugar. 
+  Lactose. 
+  Maltose. 

+  Starch. 
+  Glycogen. 
+  Dextrin. 
Cellulose. 

The  +  and  —  signs  in  the  above  list  indicate  that  the  substances 
to  which  they  are  prefixed  are  dextro-  and  Isevo-rotatory  respectively 
as  regards  polarised  light.  The  formulae  given  in  the  table  are  merely 
empirical ;  the  quantity  n  in  the  starch  group  is  variable  and  often 
large.  The  following  are  the  chief  facts  in  relation  to  each  of  the 
principal  carbohydrates. 

Dextrose,  Glucose,  or  Grape  Sugar. — This  carbohydrate  is 
found  in  many  fruits,  honey,  and  in  minute  quantities  in  the 
blood  and  numerous  tissues,  organs,  and  fluids  of  the  body.  It  is 
the  form  of  sugar  found  in  large  quantities  in  the  blood  and  urine 
in  the  disease  known  as  diabetes. 

Dextrose  is  soluble  in  hot  and  cold  water  and  in  alcohol.  It  is 
crystalline,  but  not  so  sweet  as  cane  sugar.  When  heated  with  strong 
potash  certain  complex  acids  are  formed  which  have  a  yellow  or 


410  THE   CHEMICAL  COMPOSITION   OF  THE   BODY      [CH.  XXY1II. 

brown  colour.  This  constitutes  Moore's  test  for  sugar.  In  alkaline  solu- 
tions dextrose  reduces  salts  of  silver,  bismuth,  mercury,  and  copper. 
The  reduction  of  cupric  to  cuprous  salts  constitutes  Trommer's  test, 
which  is  performed  as  follows :  put  a  few  drops  of  copper  sulphate 
into  a  test-tube,  then  solution  of  dextrose,  and  then  strong  caustic 
potash.  On  adding  the  potash  a  precipitate  is  first  formed  which 
dissolves,  forming  a  blue  solution.  On  boiling  this,  a  yellow  or  red 
precipitate  (cuprous  hydrate  or  oxide)  forms. 

On  boiling  a  solution  of  dextrose  with  an  alkaline  solution  of 
picric  acid,  a  dark  red  opaque  solution  due  to  reduction  to  picramic 
acid  is  produced. 

Another  important  property  of  grape  sugar  is  that  under  the 
influence  of  yeast  it  is  converted  into  ethyl  alcohol  and  carbonic 
acid  (CeH1206  =  2C2H60  +  2C02). 

Dextrose  may  be  estimated  by  the  fermentation  test,  by  the  polar- 
imeter,  and  by  the  use  of  Fehling's  solution.  The  last  method  is  the 
most  important :  it  rests  on  the  same  principles  as  Trommer's  test, 
and  we  shall  study  it  in  connection  with  diabetic  urine. 

Laevulose  or  Fructose. — When  cane  sugar  is  treated  with  dilute 
mineral  acids  it  undergoes  a  process  known  as  inversion — i.e.,  it 
takes  up  water  and  is  converted  into  equal  parts  of  dextrose  and 
laevulose.  The  previously  dextro-rotatory  solution  of  cane  sugar 
then  becomes  laevo-rotatory,  the  laevo-rotatory  power  of  the  Isevulose 
being  greater  than  the  dextro-rotatory  power  of  the  dextrose  formed. 
Hence  the  term  inversion.  The  same  hydrolytic  change  is  produced 
by  certain  enzymes,  such  as  the  invertase  of  the  intestinal  juice  and 
of  yeast.  Pure  Isevulose  can  be  crystallised  with  difficulty.  It  gives 
the  same  general  reactions  as  dextrose. 

Galactose  is  formed  by  the  action  of  dilute  mineral  acids  or  of 
inverting  enzymes  on  lactose.  It  resembles  dextrose  in  its  action  on 
polarised  light,  in  reducing  cupric  salts  in  Trommer's  test,  and  in 
being  directly  fermentable  with  yeast.  When  oxidised  by  means  of 
nitric  acid  it  yields  an  acid  called  mucic  acid  (C6H1008),  which  is 
only  slightly  soluble  in  water.  Dextrose  when  treated  in  this  way 
yields  an  isomeric  acid — i.e.,  an  acid  with  the  same  empirical  formula, 
called  saccharic  acid,  which  is  very  soluble  in  water. 

Cane  Sugar  is  generally  distributed  in  the  vegetable  kingdom, 
but  especially  in  the  juices  of  the  sugar  cane,  beetroot,  mallow,  and 
sugar  maple.  It  is  a  substance  of  great  importance  as  a  food.  It 
undergoes  inversion  in  the  alimentary  canal.  It  is  crystalline,  and 
dextro-rotatory.  With  Trommer's  test  it  gives  a  blue  solution,  but 
no  reduction  occurs  in  boiling.  After  inversion  it  is,  of  course, 
strongly  reducing. 

Inversion  may  be  accomplished  by  boiling  with  dilute  mineral 
acids,  or  by  means  of  inverting  enzymes  such  as  that  occurring  in  the 


CH.  XXVIII.]  THE   CARBOnYDRATES  411 

intestinal  juice.     It  then  takes  up  water,  and  is  split  into  equal  parts 
of  dextrose  and  laevulose. 


C12H22O 

[Cane  sugar.] 


H20   =   C6H1206   +    C6H1206. 

[Cane  sugar.]  [Dextrose.]  [Ltevulose.] 


With  yeast,  cane  sugar  is  first  inverted  by  means  of  a  special  enzyme 
invertase  secreted  by  the  yeast  cells,  and  then  there  is  an  alcoholic 
fermentation  of  the  monosaccharides  so  formed,  which  is  accomplished 
by  another  enzyme  called  zymase. 

Lactose,  or  Milk  Sugar,  occurs  in  milk.  It  is  occasionally 
found  in  the  urine  of  women  in  the  early  days  of  lactation,  or  after 
weaning.  It  is  crystallisable,  dextro-rotatory,  much  less  soluble  in 
water  than  other  sugars,  and  has  only  a  slightly  sweet  taste.  It 
gives  Trommer's  test,  but  when  the  reducing  power  is  tested  quanti- 
tatively by  Fehling's  solution  it  is  found  to  be  a  less  powerful  reduc- 
ing agent  than  dextrose,  in  the  proportion  of  7  to  10. 

When  hydrolysed  by  similar  agencies  as  those  mentioned  in  con- 
nection with  cane  sugar,  it  takes  up  water  and  splits  into  dextrose 
and  galactose. 

Ci2H22°n   +    H2°    =    C6H1206    +   C6H]206. 

[Lactose.]  [Dextrose.]  [Galactose.] 

With  yeast  it  is  first  inverted,  and  then  alcohol  is  formed.  This,  how- 
ever, occurs  slowly. 

The  lactic  acid  fermentation  which  occurs  when  milk  turns  sour 
is  brought  about  by  enzymes  secreted  by  certain  micro-organisms, 
which  are  somewhat  similar  to  yeast  cells.  Bacteria  in  the  intestine 
bring  about  the  same  result.  The  two  stages  of  the  lactic  acid 
fermentation  are  represented  in  the  following  equations  :  — 

(1.)  C12H22On   +   H,0   =  4CSH603. 

[Lactose.]  [Lactic  acid.] 

(2.)  4C3H603   =    2C4H802   +   4CO9   +   4H2. 

[Lactic  acid.]         [Butyric  acid.] 

Maltose  is  the  chief  end-product  of  the  action  of  malt  diastase  on 
starch,  and  is  also  formed  as  an  intermediate  product  in  the  action  of 
dilute  sulphuric  acid  on  the  same  substance.  It  is  the  chief  sugar 
formed  from  starch  by  the  diastatic  enzymes  contained  in  the  saliva 
and  pancreatic  juice.  It  can  be  obtained  in  the  form  of  acicular 
crystals,  and  is  strongly  dextro-rotatory.  It  gives  Trommer's  test  ; 
but  its  reducing  power,  as  measured  by  Fehling's  solution,  is  one-third 
less  than  that  of  dextrose.  With  yeast  it  yields  alcohol. 

By  prolonged  boiling  with  water,  or,  more  readily,  by  boiling  with 
a  dilute  mineral  acid,  or  by  means  of  an  inverting  enzymes  such  as 
occurs  in  the  intestinal  juice,  it  is  converted  into  dextrose. 

C12H9i>O11    +    H9O   =    2C6H19O(!. 

[Maltose.]  [Dextrose.] 


412  THE  CHEMICAL  COMPOSITION  OF  THE  BODY      [CH.  XXYIII. 

Phenyl-hydrazine  Test. — The  three  important  reducing  sugars 
with  which  we  have  to  deal  in  physiology  are  dextrose,  lactose,  and 
maltose.  They  may  be  distinguished  by  their  relative  reducing 
powers  on  Fehling's  solution,  or  by  the  characters  of  their  osazones. 
The  osazone  is  formed  in  each  case  by  adding  phenyl  hydrazine  hydro- 
chloride,  and  sodium  acetate,  and  boiling  the  mixture  for  about  half  an 
hour.  In  each  case  the  osazone  is  deposited  in  the  form  of  bright 
canary-coloured,  needle -like  crystals,  usually  in  bunches,  which  differ 
in  their  crystalline  form,  melting-point,  and  solubilities.  Cane  sugar 
does  not  yield  an  osazone. 

Starch  is  widely  diffused  through  the  vegetable  kingdom.  It 
occurs  in  nature  in  the  form  of  microscopic  grains,  varying  in  size  and 
appearance,  according  to  their  source.  Each 
consists  of  a  central  spot,  round  which  more  or 
less  concentric  envelopes  of  starch  proper  or 
granulose  alternate  with  layers  of  cellulose. 
Cellulose  has  very  little  digestive  value,  but 
starch  is  a  most  important  food. 

Starch  is  insoluble  in  cold  water:  it  forms 
FIG.  3i2.-Grams  of  potato     an  opalescent  solution  in  boiling  water,  which 
if    concentrated    gelatinises    on    cooling.      Its 
most    characteristic    reaction    is    the    blue    colour    it    gives   with 
iodine.    - 

On  heating  starch  with  mineral  acids,  dextrose  is  formed.  By  the 
action  of  diastatic  enzymes,  maltose  is  the  chief  end-product.  In 
both  cases  dextrin  is  an  intermediate  stage  in  the  process. 

Before  the  formation  of  dextrin  the  starch  solution  loses  its  opal- 
escence,  a  substance  called  soluble  starch  being  formed.  This,  like 
native  starch,  gives  a  blue  colour  with  iodine.  Although  the  mole- 
cular weight  of  starch  is  unknown,  the  formula  for  soluble  starch  is 
probably  5(C12H2?010)20.  Equations  that  represent  the  formation  of 
sugars  and  dextrins  from  this  are  very  complex,  and  are  at  present 
only  hypothetical. 

Dextrin  is  the  name  given  to  the  intermediate  products  in  the 
hydrolysis  of  starch  or  glycogen,  and  two  chief  varieties  are  distin- 
guished : — erythro-dextrin,  which  gives  a  reddish-brown  colour  with 
iodine ;  and  achroo -dextrin,  which  does  not. 

It  is  readily  soluble  in  water,  but  insoluble  in  alcohol  and  ether. 
It  is  gummy  and  amorphous.  It  does  not  give  Trommer's  test,  nor 
does  it  ferment  with  yeast.  It  is  dextro-rotatory.  By  hydrolysing 
agencies  it  is  converted  into  glucose. 

Glycogen,  or  animal  starch,  is  found  in  liver,  muscle,  and  white 
blood -corpuscles.  It  is  also  abundant  in  embryonic  tissues. 

Glycogen  is  a  white  tasteless  powder,  soluble  in  water,  but  it 
forms,  like  starch,  an  opalescent  solution.  It  is  insoluble  in  alcohol 


CH.  XXVni.]  THE  CAEBOHYDRATES  413 

and  ether.  It  is  dextro-rotatory.  With  Trommer's  test  it  gives  a 
blue  solution,  but  no  reduction  occurs  on  boiling. 

With  iodine  it  gives  a  reddish  or  port-wine  colour,  very  similar  to 
that  given  by  erythro-dextrin.  Dextrin  may  be  distinguished  from 
glycogen  by  (1)  the  fact  that  it  gives  a  clear,  not  an  opalescent,  solu- 
tion with  water  ;  and  (2)  it  is  not  precipitated  by  basic  lead  acetate 
as  glycogen  is.  It  is,  however,  precipitated  by  basic  lead  acetate  and 
ammonia.  (3)  Glycogen  is  precipitated  by  55  per  cent,  of  alcohol  ; 
the  dextrins  require  85  per  cent,  or  more.  (4)  It  is  precipitated 
by  saturation  with  ammonium  sulphate;  erythro-dextrin  is  only 
partially  precipitable  by  this  means. 

Cellulose.  —  This  is  the  colourless  material  of  which  the  cell-walls 
and  woody  fibres  of  plants  are  composed.  By  treatment  with  strong 
mineral  acids  it  is,  like  starch,  converted  into  glucose,  but  with  much 
greater  difficulty.  The  various  digestive  enzymes  have  little  or  no 
action  on  cellulose  ;  hence  the  necessity  of  boiling  starch  before  it  is 
taken  as  food.  Boiling  bursts  the  cellulose  envelopes  of  the  starch 
grains,  and  so  allows  the  digestive  juices  to  get  at  the  starch  proper. 
Cellulose  is  found  in  a  few  animals,  as  in  the  outer  investment  of 
the  Tunicates. 

Inosite  was  discovered  by  Scherer  in  1850  as  a  constituent  of 
muscle,  and  for  a  long  time  was  known  as  muscle  sugar.  It  occurs 
also  in  small  quantities  in  other  animal  organs  (liver,  kidney,  etc.), 
and  in  plants  it  is  a  fairly  constant  constituent  of  roots  and  leaves, 
especially  growing  leaves. 

It  has  the  same  molecular  formula  as  the  simple  sugars 
(C6H1206),  but  it  has  none  of  the  other  properties  of  these  substances. 
Maquenne  ascertained  that  it  has  the  following  formula  — 

HOH 

A 

HOH—  C          C—  HOH 
HOH—  C          C—  HOH 


HOH 

which  a  mere  glance  at  will  show  is  very  different  from  those  of  the 
sugars  given  on  p.  408.  For  the  six  carbon  atoms,  instead  of  forming 
an  open  chain,  are  linked  into  a  ring,  as  in  the  benzene  derivatives. 
It  is  in  fact  a  reduced  hexa-oxybenzene.  It  probably  represents 
a  transition  stage  between  the  carbohydrates  and  the  benzene 
compounds.  By  a  closing-up  of  the  open  chain  of  the  carbo- 


414 


THE   CHEMICAL  COMPOSITION   OF   THE   BODY      [CH.  XXVIII. 


hydrate  molecule  its  formation  from  the  latter  is  theoretically 
possible.  On  the  other  hand,  the  opening  of  the  inosite  ring 
would  give  rise  to  an  open  chain,  and  it  has  indeed  been  found 
that  lactic  acid  is  formed  from  inosite  by  the  action  of  certain 
bacteria. 


The  Pats. 

Pat  is  found  in  small  quantities  in  many  animal  tissues.  It  is, 
however,  found  in  large  quantities  in  three  situations,  viz.,  marrow, 
adipose  tissue,  and  milk. 

The  contents  of  the  fat  cells  of  adipose  tissue  are  fluid  during  life, 
the  normal  temperature  of  the  body  (37°  0.,  or  99°  F.)  being  con- 
siderably above  the  melting-point  (25°  C.)  of  the  mixture  of-  the  fats 
found  there.  These  fats  are  three  in  number,  and  are  called  palmitin, 
stearin,  and  olein.  They  differ  from  one  another  in  chemical  com- 
position and  in  certain  physical  characters,  such  as  melting-point  and 
solubilities.  Olein  solidifies  at  —  5°  C.,  palmitin  at  45°  C.,  and  stearin 
at  53-65°  C.  It  is  thus  olein  which  holds  the  other  two  dissolved  at 
the  body  temperature.  Fats  are  all  soluble  in  hot  alcohol,  ether,  and 
chloroform,  but  insoluble  in  water. 

Chemical  Constitution  of  the  Pats. — The  fats  are  compounds  of 
fatty  acids  with  glycerin,  and  may  be  termed  glycerides  or  glyceric 
ethers. 

The  fatty  acids  form  a  series  of  acids  derived  from  the  monatomic 
alcohols  by  oxidation.  Thus,  to  take  ordinary  ethyl  alcohol,  C2H60, 
the  first  stage  in  oxidation  is  the  removal  of  two  atoms  of  hydrogen 
to  form  aldehyde,  C2H40 ;  on  further  oxidation  an  atom  of  oxygen  is 
added  to  form  acetic  acid,  C2H402. 

A  similar  acid  can  be  obtained  from  all  the  other  alcohols, 
thus : — 


From  methyl  alcohol 
„     ethyl 
„     propyl 
„     butyl 
„     amyl 
„     hexyl 


CH3.HO,    formic     acid      H.COOH  is  obtained 


C.2H5.HO,  acetic 

CoH7.HO,  propionic 

C4H9.HO,  butyric 

C5Hn.HO,  valeric 

C6H13.  HO,  caproic 


CH3.COOH 
,  C2H5.COOH 
,  C,H7.COOH 
,  C4H9.COOH 
,  C5Hn.COOH 


and  so  on. 

The  sixteenth  term  of  this  series  has  the  formula  Ci5H3i.COOH, 
and  is  called  palmitic  acid ;  the  eighteenth  has  the  formula 
Ci7H35.COOH,  and  is  called  stearic  acid.  Each  acid,  as  will  be 
seen,  consists  of  a  radical,  C7i_iH2u-iCO,  united  to  hydroxyl 
(OH). 

Oleic  acid,  however,  is  not  a  member  of  this  series,  but  belongs 
to  a  somewhat  similar  series  known  as  the  acrylic  series,  of  which 


en.  XXVIIL]  THE  FATS  415 

the  general  formula  is  Cn_iH2tt_3.COOH.     It  is  the  eighteenth  term 
of  the  series,  and  its  formula  is  CnH 


The  first  member  of  the  group  of  alcohols  from  which  this  acrylic  series  of 
acids  is  obtained  is  called  allyl  alcohol  (CH2:CH.CH2OH);  the  aldehyde  of 
this  is  acrolein  (CH2:CH.CHO),  and  the  formula  for  the  acid  (acrylic  acid)  is 
CH.2:CH.COOH.  It  will  be  noticed  that  two  of  the  carbon  atoms  are  united  by 
two  valencies,  and  these  bodies  are  therefore  unsaturated  ;  they  are  unstable  and 
are  prone  to  undergo  by  uniting  with  another  element  a  conversion  into  bodies  in 
which  the  carbon  atoms  are  united  by  only  one  bond.  This  accounts  for  their 
reducing  action,  and  it  is  owing  to  this  that  the  colour  reactions  with  osmic  acid 
and  Sudan  III.  (red  coloration)  are  due.  Fat  which  contains  any  member  of  the 
acrylic  series,  such  as  oleic  acid,  blackens  osmic  acid,  by  reducing  it  to  a  lower 
(black)  oxide.  The  fats  palmitin  and  stearin  do  not  give  these  reactions. 

Glycerin  or  Glycerol  is  a  triatomic  alcohol,  C3H5(HO)3  —  i.e.,  three 
atoms  of  hydroxyl  united  to  a  radical  glyceryl  (C3H5).  The  hydrogen 
in  the  hydroxyl  atoms  is  replaceable  by  other  organic  radicals.  As 
an  example,  take  the  radical  of  acetic  acid  called  acetyl  (CH3.CO). 
The  following  formulae  represent  the  derivatives  that  can  be  obtained 
by  replacing  one,  two,  or  all  three  hydroxyl  hydrogen  atoms  in  this 
way:  — 

(OH  (OH  (OH  (O.CH,.CO 

C3HJOH    C3HJOH  C3HJO.CH3.CO     C3H5J  O.CH3.CO 

[OH  tO.CH3.CO  lO.CH3.CO  lO.CH3.CO 

[Glycerin.]  [Monoacetin.]  [Diacetin.]  [Triacetin.] 

Triacetin  is  a  type  of  a  neutral  fat;  stearin,  palmitin,  and  olein 
ought  more  properly  to  be  called  tristearin,  tripalmitin,  and  triolein 
respectively.  Each  consists  of  glycerin  in  which  the  three  atoms  of 
hydrogen  in  the  hydroxyls  are  replaced  by  radicals  of  the  fatty  acid. 
This  is  represented  in  the  following  formulae  :  — 

Acid.  Radical.  Fat. 

Palmitic  acid  C15H51.COOH  Palmityl  C]6H31.CO  Palmitin  C3H5(OC15H31.CO)3 

Stearicacid    C17H35.COOH  Stearyl    C17H35.CO  Stearin    C,H5(OC17H.,5.CO)3 

Oleic  acid       C^H^COOH  Oleyl       C^H^CO  Olein       C-jH^OC^Hgg.CO), 

Decomposition  Products  of  the  Pats.  —  The  fats  split  up  into 
the  substances  out  of  which  they  are  built  up. 

Under  the  influence  of  superheated  steam,  mineral  acids,  and  in 
the  body  by  means  of  certain  enzymes  (for  instance,  the  fat-splitting 
enzyme,  lipase,  of  the  pancreatic  juice),  a  fat  combines  with  water 
and  splits  into  glycerin  and  the  fatty  acid.  The  following  equa- 
tion represents  what  occurs  in  a  fat,  taking  tripalmitin  as  an 
example  :  — 

C3H6(O.C15H31CO)3   +   3H20   =   C3H5(OH)3   +   3C15H31CO.OH. 

[Tripalmititi—  a  fat.]  [Glycerin.]  [Palmitic  acid—  a 

fatty  acid.] 

In  the  process  of  saponiflcation  much  the  same  sort  of  reaction 
occurs,  the  final  products  being  glycerin  and  a  compound  of  the  base 


416         THE  CHEMICAL  COMPOSITION  OF  THE  BODY   [CH.  XXV III. 

with  the  fatty  acid  which  is  called  a  soap.     Suppose,  for  instance,  that 
potassium  hydrate  is  used ;  we  get — 

C3H5(O.C15H31CO)3   +   3KHO   =   C3H5(OH)3  +   3C15H31CO.OK. 

[Tripalmitin— a  fat.]  [Glycerin.]  [Potassium  palmitate— 

a  soap.] 

Enmlsification. — Another  change  that  fats  undergo  in  the  body 
is  very  different  from  saponification.  It  is  a  physical  not  a  chemical 
change;  the  fat  is  broken  up  into  very  small  globules,  such  as  are 
seen  in  the  natural  emulsion — milk. 


The  Proteins. 

The  proteins  are  the  most  important  substances  that  occur  in 
animal  and  vegetable  organisms,  and  protein  metabolism  is,  as  already 
noted  (p.  6),  the  most  characteristic  sign  of  life. 

They  are  highly  complex  compounds  of  carbon,  hydrogen,  oxygen, 
nitrogen,  and  sulphur,  occurring  in  a  solid  viscous  condition  or  in 
solution  in  nearly  all  parts  of  the  body.  The  different  members  of 
the  group  present  great  similarities,  for  instance,  in  the  heaviness  of 
their  molecules,  and  in  giving  certain  colour  tests  we  shall  be  describ- 
ing presently ;  there  are,  on  the  other  hand,  considerable  differences 
between  the  various  proteins. 

The  proteins  in  the  food  form  the  source  of  the  proteins  in  the 
body  tissues,  but  the  latter  are  usually  different  in  composition  from 
the  former.  The  food  proteins  are  in  the  process  of  digestion  broken 
up  into  simpler  substances,  usually  called  cleavage  products,  and  it  is 
from  these  that  the  body  cells  reconstruct  the  proteins  peculiar  to 
themselves.  As  a  result  of  katabolic  processes  in  the  body,  the 
proteins  are  finally  again  broken  down,  carbonic  acid,  water, 
sulphuric  acid  (combined  as  sulphates),  urea,  and  creatinine  being 
the  principal  final  products  which  are  discharged  in  the  urine  and 
other  excretions.  The  substances  intermediate  between  the  proteins 
and  these  final  katabolites  will  be  discussed  under  urine. 

The  following  figures  will  show  how  different  the  proteins  are 
even  in  elementary  composition.  Hoppe-Seyler  many  years  ago  gave 
the  variations  in  percentage  composition  as  follows : — 

C          H          N          S          O 

From 51-5        6'9         15'2        0'3        20'9 

To 54-5        7'3        17'0        2-0        23'5 

Eecent  research  has  since  shown  that  the  variations  are  even  greater 
than  those  given  by  Hoppe-Seyler. 

Differences  are  also  seen  when  the  cleavage  products  are  separ- 
ated and  estimated.  These  differ  both  in  kind  and  in  amount,  but 
nearly  all  of  them  are  substances  which  are  termed  amino-acids. 
Emil  Fischer  to  whom  we  owe  so  much  of  our  knowledge  in  this 


CH.  XXVIII.]  THE    PROTEINS  417 

direction,  considers  that  the  proteins  are  linkages  of  a  greater  or 
lesser  number  of  these  amino-acids,  and  there  is  little  doubt  that  in 
the  future  this  work  will  result  in  an  actual  synthesis  of  the  protein 
molecule,  and  with  that  will  come  an  accurate  knowledge  of  its 
constitution. 

When  the  protein  molecule  is  broken  down  in  laboratory 
processes,  or  by  the  digestive  enzymes  which  occur  in  the  alimen- 
tary canal,  the  essential  change  is  due  to  what  is  called  hydrolysis ; 
that  is,  the  molecule  unites  with  water  and  then  breaks  up  into 
smaller  molecules.  The  early  cleavage  products,  which  are  called 
proteases,  retain  many  of  the  characters  of  the  original  protein,  and 
the  same  is  true,  though  to  a  less  degree,  of  the  peptones,  which  come 
next  in  order  of  formation.  The  peptones,  in  their  turn,  are 
decomposed  into  short  linkages  of  amino-acids,  which  are  called 
polypeptides,  and  finally  the  individual  amino-acids  are  obtained 
separated  from  each  other. 

What  we  have  already  learnt  about  the  fatty  acids  will  help  us 
in  understanding  what  is  meant  by  an  amino-acid. 

If  we  take  acetic  acid,  which  is  one  of  the  simplest  of  the  fatty 
acids,  its  formula  is 

CH3 .  COOH. 

If  one  of  the  three  hydrogen  atoms  in  the  CH3  group  is  replaced 
by  NH2,  we  get  a  substance  which  has  the  formula 

CH2 .  NH2 .  COOH. 

The  combination  NH2,  which  has  stepped  in,  is  called  the  amino- 
group,  and  the  new  substance  now  formed  is  called  amino-acetic 
acid ;  it  is  also  termed  glycine  or  glycocoll. 

We  may  take  another  example  from  another  fatty  acid.  Pro- 
pionic  acid  is  C2H5 .  COOH  ;  if  we  replace  an  atom  of  hydrogen  by 
the  amino-group  as  before,  we  obtain  C2H4 .  NH2 .  COOH,  which  is 
amino-propionic  acid  or  alanine. 

If  instead  of  propionic  we  take  hydroxy-propionic  acid,  its  amino- 
derivative  (amino-hydroxy-propionic  acid)  is  termed  serine. 

A  fourth  amino-acid  is  similarly  obtained  by  the  introduction  of 
the  NH2  into  valeric  acid  C4H9 .  COOH.  Amino-valeric  acid 
C4H8 .  ISrH2 .  COOH  is  called  Valine. 

Going  to  the  next  fatty  acid  in  the  series,  caproic  acid 
C5Hn .  COOH,  we  obtain  from  it  in  an  exactly  similar  way, 
C5H10  .  NH2 .  COOH,  which  is  amino-caproic  acid  or  leucine. 

According  to  the  way  in  which  the  amino-group  is  linked,  a  large  number  of 
isomeric  amino-caproic  acids,  all  with  the  same  empirical  formula,  are  theoretically 
possible.  Many  of  these  have  been  prepared  synthetically,  and  it  has  been  shown 
that  the  amino-caproic  acid  called  leucine,  formed  by  hydrolysis  from  proteins,  is 
the  laevo-rotatory  variety,  and  should  be  more  accurately  named  a-amino-isobutyl- 

2   D 


418 


THE   CHEMICAL  COMPOSITION   OF  THE   BODY      [CH.  XXVIII. 


acetic  acid  (CH.()2CH .  CH.2(CH  .  NHo)COOH.     It  crystallises  in  spheroidal  clumps 
of  crystals,  as  shown  on  the  left-hand  side  of  fig.  318. 


FIG.  313. — Crystals  of  leucine  and  tyrosine.     x  216. 

All  the  five  amino-acids  mentioned  (glycine,  alanine,  serine,  valine, 
and  leucine)  are  found  among  the  final  products  of  most  proteins. 

A  second  group  of  amino-acids  is  obtained  from  fatty  acids, 
which  contain  two  carboxyl  (COOH)  groups  in  their  molecules. 
The  most  important  of  the  amino-derivatives  obtained  from  these 
dicarboxylic  acids  are : — 

Amino-succinamic  acid  (asparagine), 
Amino-succinic  acid  (aspartic  acid), 
Amino-pyrotartaric  acid  (glutamic  acid). 

The  third  group  of  amino-acids  is  a  very  important  one ;  these 
are  termed  the  aromatic  amino-acids ;  that  is,  amino-acids  united  to 
the  benzene  ring,  and  of  these  we  will  mention  three,  namely,  phenyl- 
alanine,  tyrosine,  and  a  nearly  related  substance  called  tryptophane. 

Phenyl-alanine  is  alanine  or  amino-propionic  acid  in  which  an 
atom  of  hydrogen  is  replaced  by  phenyl  (C6H5). 

Propionic  acid  has  the  formula  C2H5 .  COOH. 

Alanine  (amino-propionic  acid)  is  C2H4NH2 .  COOH. 

Phenyl-alanine  is  C2H3 .  C6H5 .  NH2 .  COOH. 

The  formula  of  phenyl-alanine  may  also  be  written  another  way. 
The  graphic  formula  of  benzene  (C6H6)  is : — 

H 


H  —  C 


H  —  C 


C  — H 
C  — H 


OH.  XXVIII.] 


AMINO-ACIDS 


419 


If  the  H  placed  lowermost  in  the  above  formula  is  replaced  by 
CH2CH  .  NH., .  CO  OH,  we  obtain  the  formula  of  phenyl-alanine : — 


CH2 .  CHNH2COOH 

the  remainder  of  the  benzene  ring,  which  is  unaltered,  being  repre- 
sented as  usual  by  a  simple  hexagon. 

Tyrosine  is  a  li  ttle  more  complicated ;  it  is  oxyphenyl-alanine ; 
that  is,  instead  of  phenyl  (CGH5)  in  the  formula  of  phenyl-alanine, 
we  have  now  oxyphenyl  (C6H4  .  OH) ;  this  gives  us 


C2H8 


(C6H4.OH)NH2.COOH 


as  the  formula  for  tyrosine  written  one  way,  or 

HO 


CH2 .  CHNH2 .  COOH 

when  written  in  the  other  way.     Tyrosine  crystallises  in  collections 
of  very  fine  needles  (see  fig.  313). 

Tryptophane  is  more  complex  still ;  it  is  indole  amino-propionic 
acid :  that  is,  amino-propionic  acid  united  to  another  ringed  deriva- 
tive called  indole.  Tryptophane  is  the  portion  of  the  protein 
molecule  which  is  the  parent  substance  of  two  evil-smelling  products 
of  protein  decomposition  called  indole  and  scatole  or  methyl  indole. 
Indole  is  a  combination  of  the  benzene  and  pyrrol  rings  as  shown 
below : — 

CH 
/I 
HC 


HC\ 


/CH 


Tryptophane  is  the  radical  in  the  protein  molecule  which  is 
responsible  for  the  colour  test  called  the  Adamkiewicz  reaction. 

In  all  the  preceding  cases,  there  is  only  one  replacement  of  an 
atom  of  hydrogen  by  NH2 ;  hence  they  may  be-  all  grouped  together 
as  mono-amino-acids. 

Passing  to  the  next  stage  in  complexity,  we  come  to  another  group 


420  THE   CHEMICAL   COMPOSITION   OF  THE   BODY      [CH.  XXVIII. 

of  amino-acids  which  are  called  dmramo-acids  ;  that  is,  fatty  acids  in 
which  two  hydrogen  atoms  are  replaced  by  NH2  groups.  Of  these  we 
may  particularly  mention  lysine,  ornithine,  arginine,  and  histidine. 

Lysine  is  diamino-caproic  acid.  Caproic  acid  is  C5Hn  .  COOH. 
.Mono-amino-caproic  acid  or  leucine,  we  have  already  learnt,  is 
CJEL0  .  NIL  .  COOH.  Lysine  or  diamino-caproic  acid  is  C  JHL  . 
(NH2)2.COOH. 

Ornithine  is  diamino-valeric  acid,  and  the  following  formulae 
will  show  its  relationship  to  its  parent  fatty  acid  — 

C4H9GOOH  is  valeric  acid. 

C4H7(NU2)2COOH  is  diamino-valeric  acid  or  ornithine. 

Arginine  is  a  somewhat  more  complex  substance,  which  contains 
the  ornithine  radical.  It  belongs  to  the  same  group  of  substances  as 
creatine,  another  important  cleavage  product  of  the  protein  molecule. 
Creatine  is  methyl-guanidine  acetic  acid,  and  has  the  formula 


;  —  N(CH3)CH2  .  COOH 


H2N 


On  boiling  it  with  baryta  water,  it  takes  up  water  (H20)  and  splits  at 
the  dotted  line  into  urea  (CO(NH2)2)  and  sarcosine,  as  shown  below. 


H2N 


C— O 


NH.CHQ.CH0.COOH 


[Urea.]  [Sarcosine  or  Methyl-glycine.] 

Arginine  splits  in  a  similar  way,  urea  being  split  off  on  the  left, 
and  ornithine  instead  of  sarcosine  on  the  right.  Arginine  is,  there- 
fore, a  compound  of  ornithine  with  a  urea  group. 

Histidine,  though  not  strictly  speaking  a  diamino-acid,  is  a 
diazine  derivative  (imidazole  -  amino  -  propionic  acid),  and  so  may 
be  included  in  the  same  group. 

These  substances  we  have  spoken  of  as  acids,  but  they  may  also 
play  the  part  of  bases,  for  the  introduction  of  a  second  amino-group 
into  the  fatty  acid  molecules  confers  upon  them  basic  properties. 
The  three  substances, 

Lysine  .         .         C6H14N2O2 

Arginine          .         .          C6H14N4O2 
Histidine         .         .         C6H9N3O2 

are  in   fact   often   called  the   hexone   bases,  because   each  of   them 
contains  6  atoms  of  carbon,  as  the  above  empirical  formulae  show. 


CH.  XXVIII.]  AMINO- ACIDS  421 

Cystine  is  a  complex  diamino-acid  in  which  sulphur  is  present, 
and  in  which  the  greater  part  of  the  sulphur  of  the  protein  molecule 
is  contained. 

In  addition  to  all  these  numerous  amino-acids  there  are  other 
cleavage  products,  of  which  it  will  be  sufficient  to  mention  proline 
and  ammonia.  In  the  case  of  the  nucleo-proteins  the  nuclein 
component  yields  in  addition  what  are  known  as  purine  and 
pyrimidine  bases.  (See  further  under  nucleic  acid,  p.  431,  also 
under  uric  acid,  Chapter  XXXIX.) 

Proline  and  the  purine  and  pyrimidine  bases  are  all  derivatives 
of  rings  which  remind  one  of  the  benzene  ring,  except  that  nitrogen 
is  included  in  the  ring  formation ;  such  rings  are  termed  heterocyclic. 
Thus  proline  (pyrrolidine-carboxylic  acid)  is  a  derivative  of  the 
pyrrol  ring,  and  its  formula  is  given  below.  Cytosine  is  one  of  the 
derivatives  of  the  pyrimidine  ring,  and  hypoxanthine  (or  oxypurine) 
is  given  below  as  an  example  of  the  purine  bases. 

H9O-CH2  HN— C .  NH2 

"II  II 

H9C     CH.COOH  OC     CH 

\/  I       II 

N  HN— CH  N- 

[Cytosine  or  amino-  [Hypoxanthine.] 

oxypyrimidine.] 

[Proline.] 

Our  list  now  represents  the  principal  groups  of  chemical  nuclei 
united  together  in  the  protein  molecule,  and  its  length  makes  one 
realise  the  complicated  nature  of  that  molecule  and  the  difficulties 
which  beset  its  investigation.  We  may  put  the  problem  another 
way.  In  the  simple  sugars,  with  six  atoms  of  carbon,  there  are  as 
many  as  thirty-six  different  ways  in  which  the  atomic  groups  may 
be  linked  up ;  the  formulas  on  p.  408  give  only  three  of  these  which 
represent  the  structure  of  dextrose,  Isevulose,  and  galactose  ;  but  the 
majority  of  the  remainder  have  also  been  prepared  by  chemists.  The 
molecule  of  albumin  has  at  least  700  carbon  atoms,  so  the  possible 
combinations  and  permutations  must  be  reckoned  by  thousands. 

The  workers  in  Fischer's  laboratory  are  steadily  working  through 
the  various  known  proteins,  taking  them  to  pieces  and  identifying 
and  estimating  the  fragments.  I  do  not  intend  to  burden  the 
readers  of  this  book  with  anything  more  than  a  sample  of  their 
results,  and  will,  therefore,  only  give  in  a  brief  table  (see  page 
422)  the  results  obtained  with  some  of  the  cleavage  products  of  a 
few  proteins.  The  numbers  given  are  percentages. 

Such  numbers,  of  course,  are  not  to  be  committed  to  memory,  but 
they  are  sufficient  to  convey  to  the  reader  the  differences  between 
the  proteins.  There  are  several  blanks  left,  on  account  of  no  accurate 


422 


THE   CHEMICAL   COMPOSITION   OF   THE   BODY      [CH.    XXVIII. 


estimations  having  yet  been  made.  Where  the  sign  +  occurs,  the 
substance  in  question  has  been  proved  to  be  present,  but  not  yet 
determined  quantitatively.  Among  the  more  striking  points  brought 
out  are : — 

1.  The  absence  of  glycine  from  albumins. 

2.  The  high  percentage  of  glycine  in  gelatin. 

3.  The  absence  of  tyrosine  and  tryptophane  in  gelatin. 

4.  The   high   percentage   of    the    sulphur-containing    substance 
(cystine)  in  keratin. 

5.  The  high  percentage  of  glutamic  acid  in  vegetable  proteins. 


.a 

g 

d 

o    . 

Q 

|l 

1 

a 

§ 

| 

i 

a~$ 

. 

.2.~ 

o  K 

a 

o 

8 

£ 

_o 

3 
| 

II 

1 

|| 

fi"8 

I 

i"? 

bO 

1 
1 

o  ° 

&* 

"«  8 

1 

0 

Glycine 
Leucine 

0 
20-0 

0 
6-1 

3-5 
18-7 

0 
10-5 

16-5 
2-1 

4-7 

1-2 
15-5 

0 
18-6 

0'02 
5-6 

Glutamic  acid   . 

7'7 

8-0 

8-5 

11-0 

0-9 

3-7 

17-2 

18-3 

37-3 

Tyrosine    . 
Arginine   . 

2-1 

1-1 

2-5 

4-5 
4-8 

0 
7-6 

3-2 

2-1 
11-7 

3-5 
1-2 

1-2 
3-2 

Tryptophane     . 

+ 

+ 

+. 

1-5 

0 

+ 

0 

+ 

Cystine     . 

2-5 

0-3 

0-7 

0-06 

-{ 

More 
than  10 

}  0-2 

0-4 

Emil  Fischer,  Abderhalden,  T.  B.  Osborne,  Levene,  van  Slyke,  and 
others  are  attempting  to  make  the  list  complete,  and  are  devising 
new  and  more  accurate  methods  of  analysis.  Fischer  has  also 
discovered  the  way  in  which  the  amino-acids  are  linked  together  into 
groups ;  and  the  culmination  of  his  work  will  be  the  discovery  of  the 
way  in  which  such  groups  are  linked  together  to  form  the  protein 
molecule.  The  last  stage  has  not  yet  been  reached,  but  it  will  be 
interesting  to  see  how  the  amino-acids  are  linked  together  into 
groups. 

The  groups  are  termed  peptides  or  polypeptides ;  many  of  these 
have  been  made  synthetically  in  his  laboratory,  and  so  the  synthesis 
of  the  protein  molecule  is  foreshadowed. 

We  may  take  as  our  examples  of  the  peptides  some  of  the  simplest, 
and  may  write  the  formulae  of  a  few  amino-acids  as  follows : — 
NH0 .  CH2 .  COOH         Glycine 
^  .  C2H4  .  COOH        Alaiiine 


NH0 .  CCH1A  .  COOH       Leucine 


or  in  general  terms 


HNH.R.COOH. 


CH.  XXVIII.]  PROTEIN    CLEAVAGE   PRODUCTS  423 

Two  amino-acids  are  linked  together  as  shown  in  the  following 
formula : — 

HNH  .  R .  CO  i  OH .  H ' NH . R .  COOH 


What  happens  is  that  the  hydroxyl  (OH)  of  the  carboxyl  (COOH) 
group  of  one  acid  unites  with  one  atom  of  the  hydrogen  of  the  next 
amino  (HNH)  group,  and  water  is  thus  formed,  as  shown  within  the 
dotted  lines:  this  is  eliminated  and  the  rest  of  the  chain  closes  up. 
In  this  way  we  get  a  dipeptide.  The  names  glycyl,  alanyl,  leucyl, 
etc.,  are  given  by  Fischer  to  the  NH2 .  E .  CO  groups  which  replace 
the  hydrogen  of  the  next  NH2  group.  Thus  glycyl-glycine,  glycyl- 
leucine,  leucyl-alanine,  alanyl-leucine,  and  numerous  other  combina- 
tions are  obtained.  If  the  same  operation  is  repeated  we  obtain 
tripeptides  (leucyl-glycyl-alanine,  alanyl -leucyl-tyrosine,  etc.);  then 
come  the  tetrapeptides,  and  so  on.  In  the  end,  by  coupling  the 
chains  sufficiently  often  and  in  appropriate  order,  Fischer  has  already 
obtained  substances  which  give  some  of  the  reactions  of  peptone. 

Hausmann's  Method. — This  is  a  short  and  trustworthy  procedure,  by  which 
an  approximate  knowledge  of  the  nitrogen  distribution  in  the  protein  molecule 
is  ascertained. 

It  is^  shortly  as  follows  :— The  whole  nitrogen  of  the  protein  is  estimated  by 
Kjeldahl's  method.  A  weighed  amount  is  then  hydrolysed  by  means  of  hydro- 
chloric acid,  and  then  the  cleavage  products  are  separated  into  three  classes  and 
the  nitrogen  estimated  in  each,  as — 

1.  Ammonia  nitrogen.     This  comprises  the  nitrogen  of  the  protein  molecule 
which   is   easily  split   off  as   ammonia,  and  is  determined   by   distilling  off  the 
ammonia  with  magnesia. 

2.  Diamino-N.     The  fluid,  free  from  ammonia,  is  precipitated  by  phospho- 
tungstic  acid,   and  the  nitrogen   present  in   the   precipitate   determined.      This 
represents  the  nitrogen  of  the  diamino-acids  (lysine,  arginine,  etc.). 

3.  Mono-amino-N  is  then  estimated  in  the  residual  fluid. 

The  method  has  proved  useful  for  the  differentiation  of  proteins,  and  interest- 
ing deductions  as  to  their  food  value  has  been  drawn  from  its  results. 

Solubilities. — The  proteins  are  insoluble  in  alcohol  and  ether. 
Some  are  soluble  in  water,*  others  insoluble.  Many  of  the  latter  are 
soluble  in  weak  saline  solutions.  Some  are  insoluble,  others  soluble 
in  concentrated  saline  solutions. 

All  proteins  are  soluble  with  the  aid  of  heat  in  concentrated 
mineral  acids  and  alkalis.  Such  treatment,  however,  decomposes  as 
well  as  dissolves  the  protein.  Proteins  are  also  soluble  in  gastric  and 
pancreatic  juices ;  but  here,  again,  they  undergo  a  change,  as  we  have 
already  seen. 

Heat  Coagulation. — Most  native  proteins,  such  as  white  of  egg, 

*  The  proteins  are  not  truly  soluble  in  water.;  they  are  in  a  state  of  colloidal 
solution*  a  condition  intermediate  between  true  solution  and  suspension.  Many  of 
their  properties  are  due  to  this  fact. 


424 


THE   CHEMICAL  COMPOSITION  OF  THE   BODY      [CH.  XXVIII. 


are  rendered  insoluble  when  their  solutions  are  heated.  The  tempera- 
ture of  heat  coagulation  differs  in  different  proteins ;  thus  myosinogen 
and  fibrinogen  coagulate  at  56°  C.,  serum  albumin  and  serum  globulin 
at  about  75°  C. 

The  proteins  which  are  coagulated  by  heat  come  mainly  under  two 
the  albumins  and  the  globulins.  These  differ  in  solubility ; 
the  albumins  are  soluble  in  distilled  water,  the  true  globulins  require 
salts  to  hold  them  in  solution. 

Indiffusibility. — The  proteins  (peptones  excepted)  belong  to  the 
class  of  substances  called  colloids  by  Thomas  Graham ;  that  is,  they 

pass  with  difficulty,  or  not  at  all,  through 
animal  membranes.  In  the  construction  of 
dialysers,  vegetable  parchment  is  largely 
used. 

Proteins  may  thus  be  separated  from 
diffusible  (crystalloid)  substances  such  as 
salts,  but  the  process  is  a  tedious  one.  If 
some  serum  or  white  of  egg  is  placed  in  a 
dialyser  (fig.  314)  and  distilled  water  out- 
side, the  greater  amount  of  the  salts  passes 
into  the  water  through  the  membrane  and 
is  replaced  by  water;  the  two  proteins 
albumin  and  globulin  remain  inside;  the 
globulin  is,  however,  precipitated,  as  the 
salts  which  previously  kept  it  in  solution 
are  removed. 

Crystallisation. — Haemoglobin,  the  red 
pigment  of  the  blood,  is  a  protein  substance 
and  is  crystallisable  (for  further  details, 
see  The  Blood,  Chapter  XXIX.).  Like 
other  proteins  it  has  an  enormously  large 
molecule  ;  though  crystalline,  it  is  not 
crystalloid  in  Graham's  sense  of  that  term.  Blood  pigment,  however, 
is  not  the  only  crystallisable  protein.  Long  ago  crystals  of  protein 
(globulin  or  vitellin)  were  observed  in  the  aleurone  grains  of  many 
seeds,  and  in  the  somewhat  similar  granules  occurring  in  the  egg-yolk 
of  some  fishes  and  amphibians.  By  appropriate  methods  these  have 
been  separated  and  recrystallised.  Further,  egg  albumin  itself  has 
been  crystallised.  If  a  solution  of  white  of  egg  is  diluted  with  an 
equal  volume  of  saturated  solution  of  ammonium  sulphate,  the  globulin 
present  is  precipitated  and  is  removed  by  filtration.  The  filtrate  is 
now  allowed  to  remain  some  days  at  the  temperature  of  the  air,  and 
as  it  becomes  more  concentrated  from  evaporation,  minute  spheroidal 
globules  and  finally  minute  needles,  either  aggregated  or  separate, 
make  their  appearance  (Hofmeister).  Crystallisation  is  more  rapid  if 


FIG.  314.— Dialyser  made  of  a  tube 
of  parchment  paper,  suspended 
in  a  vessel  through  which  water 
is  kept  flowing. 


CII.   XXVIII.]  PROPERTIES    OF  PROTEINS  425 

a  little  acetic  or  sulphuric  acid  is  added  (Hopkins).  Serum  albumin 
(from  some  animals)  has  also  been  similarly  crystallised  (Giirber). 

Action  on  Polarised  Light. — All  proteins  are  Isevo-rotatory,  the 
amount  of  rotation  varying  with  individual  proteins.  Several  of  the 
conjugated  proteins,  e.g.,  haemoglobin  and  nucleo-proteins,  are  dextro- 
rotatory, though  their  protein  components  are  Isevo-rotatory  (Gamgee). 

Colour  Reactions. — The  principal  colour  reactions  by  which 
proteins  are  recognised  are  the  following: — 

(1)  The  xantho-proteic  reaction;   if  nitric   acid   is   added   to   a 
solution  of  a  protein  such  as  white  of  egg,  the  result  is  a  white 
precipitate;   this  and    the   surrounding   liquid    become    yellow   on 
boiling   and   are    turned    orange    by  ammonia.      The    preliminary 
white  precipitate  is  not  given  by  certain  proteins  such  as  peptones ; 
but  the  colours  are  the  same.     The  colour  is  due  to  the  formation 
of    nitro-derivatives   from    the    aromatic    portion    of    the    protein 
molecule. 

(2)  Millon's  reaction.     Millon's  reagent  is  a  mixture  of  mercuric 
and  mercurous  nitrate  with   excess  of  nitric   acid.      This  gives   a 
white  precipitate  which  is  turned  brick -red  on  boiling.    This  reaction 
depends  on  the  presence  of  the  tyrosine  radical. 

(3)  Copper  sulphate  (Hose's  or  Piotrowski's)  test.     A  trace  of  copper 
sulphate  and  excess  of  strong  caustic  potash  give  with  most  proteins 
a  violet  solution.     Proteoses  and  peptones,  however,  give  a  rose-red 
colour  instead;   this  same  colour  is  given  by  the   substance  called 
"biuret ;  hence  the  test  is  generally  called  the  "biuret  reaction.     This 
name  does  not  imply  that  biuret  is  present  in  protein;   but  both 
protein  and  biuret  give  the  reaction  because  they  possess  a  common 
radical,  namely,  two  CONH2  groups  linked  to  a  carbon  or  nitrogen 
atom,  or  to  one  another.     The  native  proteins  give  a  violet  colour, 
because  the  red  tint  of  the  copper  compound  with  the  biuret  group 
is  mixed  with  another  copper  compound  with  a  blue  colour. 

Biuret  is  formed  by  heating  solid  urea  ;  ammonia  passes  off  and  leaves  biuret, 
thus  : — 

2CON2H4   =    C202N3H5   +    NH3. 

[Urea.]  [Biuret.]  [Ammonia.] 

(4)  Adamkiewicz  reaction*     When  a  solution  of  protein  is  mixed 
with  a  dilute  solution  of  formaldehyde,  and  then  excess  of  commercial 
sulphuric  acid  is  added,  an  intense  violet  colour  is  obtained.     This 
is  due  to  the  tryptophane  radical. 

Precipitants  of  Proteins. — Solutions  of  most  proteins  are  pre- 
cipitated by: — 

*  In  the  original  test,  glacial  acetic  acid  was  used,  but  it  is  really  an  impurity 
in  this  acid  that  gives  the  reaction.  Rosenheim  was  the  first  to  show  that  this 
impurity  is  formaldehyde.  The  presence  of  impurities  (oxidising  agents)  in  the 
sulphuric  acid  is  also  necessary. 


426  THE  CHEMICAL  COMPOSITION   OF  THE  BODY       [CH.  XXV11I. 

Strong  acids  such  as  nitric  acid ;  picric  acid ;  acetic  acid  and 
potassium  ferrocyanide ;  acetic  acid  and  excess  of  a  neutral  salt  such 
as  sodium  sulphate,  when  these  are  boiled  with  the  protein  solution ; 
salts  of  the  heavy  metals  such  as  copper  sulphate,  mercuric  chloride, 
lead  acetate,  silver  nitrate,  etc. ;  tannin ;  alcohol ;  saturation  with 
certain  neutral  salts  such  as  ammonium  sulphate. 

It  is  necessary  that  the  words  coagulation  and  precipitation  should 
in  connection  with  proteins  be  carefully  distinguished.  The  term 
coagulation  is  used  when  an  insoluble  protein  (coagulated  protein)  is 
formed  from  a  soluble  one.  This  may  occur : 

1.  When  a  protein  is  heated — heat  coagulation  ; 

2.  Under   the   influence   of   an   enzyme;   for  instance,   when   a 
curd  is  formed  in  milk  by  rennet  or  a  clot  in  shed  blood  by  the  fibrin 
ferment — enzyme  coagulation  ; 

3.  When  an  insoluble  precipitate  is  produced  by  the  addition  of 
certain  reagents  (nitric  acid,  picric  acid,  tannin,  etc.). 

There  are,  however,  other  precipitants  of  proteins  in  which  the 
precipitate  formed  is  readily  soluble  in  suitable  reagents  such  as  saline 
solutions,  and  the  protein  continues  to  show  its  typical  reactions. 
This  is  not  coagulation.  Such  a  precipitate  is  produced  by  satura- 
tion with  ammonium  sulphate.  Certain  proteins,  called  globulins, 
are  more  readily  precipitated  by  such  means  than  others.  Thus, 
globulins  are  precipitated  by  half  -  saturation  with  ammonium 
sulphate.  Full  saturation  with  ammonium  sulphate  precipitates  all 
proteins  but  peptone.  The  globulins  are  precipitated  by  certain 
salts,  such  as  sodium  chloride  and  magnesium  sulphate,  which  do 
not  precipitate  the  albumins.  This  method  of  precipitation  is  called 
"salting  out." 

The  precipitation  produced  by  alcohol  is  peculiar  in  that  after  a 
time  it  becomes  a  coagulation.  Protein  freshly  precipitated  by 
alcohol  is  readily  soluble  in  water  or  saline  media ;  but  after  it  has 
been  allowed  to  stand  some  time  under  alcohol  it  becomes  more  and 
more  insoluble.  Albumins  and  globulins  are  most  readily  rendered 
insoluble  by  this  method ;  proteoses  and  peptones  are  never  rendered 
insoluble  by  the  action  of  alcohol.  This  fact  is  of  value  in  the 
separation  of  these  proteins  from  others. 

CLASSIFICATION  OF  PKOTEINS. 

The  knowledge  of  the  chemistry  of  the  proteins,  which  is  slowly 
progressing  under  Emil  Fischer's  leadership,  will,  no  doubt,  in  time 
enable  us  to  give  a  classification  of  these  substances  on  a  strictly 
chemical  basis.  The  following  classification  must  therefore  be 
regarded  as  a  provisional  one,  which,  while  it  retains  the  old 
familiar  names  as  far  as  possible,  yet  attempts  also  to  incorporate 
some  of  the  new  ideas. 


CH.  XXVIII.]  CLASSIFICATION   OF  PROTEINS  427 

The  classes  of  animal  proteins,  then,  beginning  with  the  simplest, 
are  as  follows : — 

1.  Protamines.  6.  Phospho-proteins. 

2.  Histones.  7.  Conjugated  proteins. 

3.  Albumins.  i.  Chromo-proteins. 

4.  Globulins.  ii.  Gluco-proteins. 

5.  Sclero-proteins.  iii.  Nucleo-proteins. 

1.  The  Protamines. 

These  substances  are  obtainable  from  the  heads  of  the  spermatozoa 
of  certain  fishes,  where  they  occur  in  combination  with  nuclein. 
Kossel's  view  that  they  are  the  simplest  proteins  in  nature  has  met 
with  general  acceptance,  and  they  give  such  typical  protein  reactions 
as  the  copper  sulphate  test  (Kose's  or  Piotrowski's  reaction).  On 
hydrolytic  decomposition  they  first  yield  substances  of  smaller 
molecular  weight  analogous  to  the  peptones  which  are  called  protones, 
and  then  they  split  up  into  amino-acids.  The  number  of  resulting 
ammo-acids  is  small  as  compared  with  other  proteins,  hence  the 
hypothesis  that  they  are  simple  proteins  is  confirmed.  Notable 
among  their  decomposition  products  are  the  diamino-acids  or  hexone 
bases,  especially  arginine. 

The  protamines  differ  in  their  composition  according  to  their 
source,  and  yield  these  products  in  different  proportions. 

Salmine  (from  the  salmon  roe)  and  clupeine  (from  the  herring  roe)  appear  to  be 
identical,  and  have  the  empirical  formula  C.?0H57N17O6 ;  its  principal  decomposi- 
tion product  is  arginine,  but  amino- valeric  acid  and  a  small  quantity  of  serine  and 
proline  are  also  found.  Sturine  (from  the  sturgeon)  yields  the  same  products  with 
lysine  and  histidine  in  addition.  With  one  exception,  the  protamines  yield  no 
aromatic  amino-acids.  The  exception  is  cyclopterine  (from  Cyclopterus  lumptus] ; 
this  substance  is  thus  an  important  chemical  link  between  the  other  protamines 
and  the  more  complex  members  of  the  protein  family. 

2.  The  Histones. 

These  are  substances  which  have  been  separated  from  blood- 
corpuscles  ;  globin,  the  protein  constituent  of  haemoglobin,  is  a  well- 
marked  instance.  They  yield  a  larger  number  of  amino-compounds 
than  do  the  protamines,  but  diamino-acids  are  relatively  abundant. 
They  are  coagulable  by  heat,  soluble  in  dilute  acids,  and  precipitable 
from  such  solutions  by  ammonia.  The  precipitability  by  ammonia  is 
a  property  possessed  by  no  other  protein  group. 

3.  The  Albumins. 

These  are  typical  proteins,  and  yield  the  majority  of  the  cleavage 
products  already  enumerated. 


428 


THE  CHEMICAL  COMPOSITION  OF  THE  BODY      [CH.  XXVIII. 


They  enter  into  colloidal  solution  in  water,  in  dilute  saline  solu- 
tions, and  in  saturated  solutions  of  sodium  chloride  and  magnesium 
sulphate.  They  are,  however,  precipitated  by  saturating  their 
solutions  with  ammonium  sulphate.  Their  solutions  are  coagulated 
by  heat,  usually  at  70-73°  C.  Serum  albumin,  egg  albumin,  and 
lact -albumin  are  instances. 


4.  The  Globulins. 

The  globulins  give  the  same  general  tests  as  the  albumins ;  they 
are  coagulated  by  heat,  but  differ  from  the  albumins  mainly  in  their 
solubilities.  This  difference  in  solubility  may  be  stated  in  tabular 
form  as  follows : — 


Reagent. 

Albumin. 

Globulin. 

Water     
Dilute  saline  solution     .... 
Saturated  solution  of  magnesium  sul- 
phate or  sodium  chloride  . 
Half-saturated  solution  of  ammonium 

soluble 
soluble 

soluble 
soluble 

insoluble 
soluble 

insoluble 
insoluble 

Saturated  solution  of  ammonium  sul- 
phate          

insoluble 

insoluble 

Globulins  are  more  readily  salted  out  than  albumins;  they 
may  therefore  be  precipitated,  and  thus  separated  from  the  albumins 
by  saturation  with  such  salts  as  sodium  chloride,  or  better  magnesium 
sulphate,  or  by  half  saturation  with  ammonium  sulphate. 

The  typical  globulins  are  also  insoluble  in  water,  and  so  may  be 
precipitated  by  removing  the  salt  which  keeps  them  in  solution. 
This  may  be  accomplished  by  dialysis  (see  p.  424).  Their  temperature 
of  heat-coagulation  varies  considerably.  The  following  are  the 
commoner  globulins : — fibrinogen  and  serum  globulin  in  blood,  egg 
globulin  in  white  of  egg,  paramyosinogen  in  muscle,  and  crystallin  in 
the  crystalline  lens.  We  must  also  include  under  the  same  heading 
certain  proteins  which  are  the  result  of  enzyme  coagulation  on 
globulins,  such  as  fibrin  (see  blood)  and  myosin  (see  muscle). 

The  most  striking  and  real  distinction  between  globulins  and 
albumins  is  that  the  former  on  hydrolysis  yield  glycine,  whereas  the 
albumins  do  not. 

5.  The  Sclero-proteins. 

These  substances  form  a  heterogeneous  group  of  substances, 
which  are  frequently  termed  albuminoids.  The  prefix  sclero  indicates 


CH.  XXVIII.]  THE   PHOSPHO-PROTEINS  429 

the  skeletal  origin  and  often  insoluble  nature  of  the  members  of  the 
group.  The  principal  proteins  under  this  head  are : — 

Collagen,  the  substance  of  which  the  white  fibres  of  connective 
tissue  are  composed.  Some  observers  regard  it  as  the  anhydride  of 
gelatin.  In  bone  it  is  often  called  ossein. 

Gelatin. — This  substance  is  produced  by  boiling  collagen  with 
water.  It  possesses  the  peculiar  property  of  setting  into  a  jelly  when 
a  solution  made  with  hot  water  cools.  On  digestion  it  is  like  ordinary 
proteins  converted  into  peptone-like  substances,  and  is  readily 
absorbed.  Though  it  will  replace  in  diet  a  certain  quantity  of  such 
proteins,  acting  as  what  is  called  a  "  protein-sparing  "  food,  it  cannot 
altogether  take  their  place  as  a  food.  Animals  whose  sole  nitrogenous 
food  is  gelatin  waste  rapidly.  The  reason  for  this  is  that  "gelatin 
contains  neither  the  tyrosine  or  the  tryptophane  groups,  and  so  it 
gives  neither  Millon's  nor  the  Adamkiewicz  reactions.  Animals  who 
receive  a  mixture  of  gelatin,  tyrosine,  and  tryptophane  in  their  diet 
thrive  better. 

Chondrin  is  the  name  given  to  the  mixture  of  gelatin  and  mucoid 
which  is  obtained  by  boiling  cartilage. 

Elastin. — This  is  the  substance  of  which  the  yellow  or  elastic 
fibres  of  connective  tissue  are  composed.  It  is  a  very  insoluble 
material.  The  sarcolemma  of  muscular  fibres  and  certain  basement 
membranes  are  very  similar. 

Keratin,  or  horny  material,  is  the  substance  found  in  the  surface 
layers  of  the  epidermis,  in  hairs,  nails,  hoofs,  and  horns.  It  is  very 
insoluble,  and  chiefly  differs  from  most  other  proteins  in  its  high 
percentage  of  sulphur.  A  similar  substance,  called  neurokeratin,  is 
found  in  neuroglia  and  nerve-fibres.  In  this  connection  it  is  interest- 
ing to  note  that  the  epidermis  and  the  nervous  system  are  both 
formed  from  the  same  layer  of  the  embryo — the  epiblast. 

6.  The  Phospho -proteins. 

Vitellin  (from  egg-yolk),  caseinogen,  the  principal  protein  of 
milk,  and  casein,  the  result  of  the  action  of  the  rennet-enzyme 
on  caseinogen  (see  milk),  are  the  chief  members  of  this  group. 
Among  their  decomposition  products  is  a  considerable  quantity  of 
phosphoric  acid.  They  have  been  frequently  confused  with  the 
nucleo-proteins,  and  the  prefix  nucleo — so  often  applied  to  them — 
is  entirely  misleading,  since  they  do  not  yield  the  products  (purine 
bases,  etc.)  which  are  characteristic  of  nucleo-compounds.  The 
phosphorus  is  contained  within  the  protein  molecule,  and  not  in 
another  molecular  group  united  to  the  protein,  as  is  the  case  in  the 
nucleo-proteins.  The  phospho-proteins  are  specially  valuable  for  the 
growth  of  young  and  embryonic  animals. 


430  THE   CHEMICAL   COMPOSITION   OF   THE   BODY      [CH.  XXVIII. 


7.  The  Conjugated  Proteins. 

These  are  compounds  in  which  the  protein  molecule  is  united  to 
other  organic  materials,  which  are  as  a  rule  also  of  complex  nature. 
This  second  constituent  of  the  compound  is  usually  termed  a  pros- 
thetic group.  They  may  be  divided  into  the  following  sub-classes : — 

i.  Chromo-proteins. — These  are  compounds  of  protein  with  a 
pigment,  which  usually  contains  iron.  They  are  typified  by  haemo- 
globin and  its  allies,  which  will  be  fully  considered  under  Blood. 

ii.  Gluco-proteins. — These  are  compounds  of  protein  with  a 
carbohydrate  group.  This  class  includes  the  mucins  and  the  mucoids. 

The  mucins  are  widely  distributed  and  may  occur  in  epithelial 
cells,  or  be  shed  out  by  these  cells  (mucus,  mucous  glands,  goblet 
cells).  The  mucins  obtained  from  different  sources  are  alike  in  being 
viscid  and  tenacious,  soluble  in  dilute  alkalis  such  as  lime  water, 
and  precipitable  from  solution  by  acetic  acid. 

The  mucoids  differ  from  the  mucins  in  minor  details.  The  term 
is  applied  to  the  mucin-like  substances  which  form  the  chief  con- 
stituent of  the  ground  substance  of  connective  tissues  (tendo-mucoid, 
chondro-mucoid,  etc.).  Another  (ovo-mucoid)  is  found  in  white  of 
egg,  and  others  (pseudo-mucin  and  para-mucin)  are  occasionally  found 
in  dropsical  effusions,  and  in  the  fluid  of  ovarian  cysts. 

The  differences  between  the  mucins  and  mucoids  are  due  either 
to  the  nature  of  the  carbohydrate  group,  or  more  probably  to  the 
nature  of  the  protein  to  which  it  is  united.  The  carbohydrate 
substance,  however,  is  not  sugar,  but  a  nitrogenous  substance 
which  has  a  similar  reducing  power  to  sugar,  and  which  is  called 
glucosamine  (C6H1105NH2),  that  is,  glucose  in  which  HO  is  replaced 
by  NH2. 

Pavy  and  others  have  shown  that  a  small  quantity  of  the  same 
carbohydrate  derivative  can  be  split  off  from  various  other  proteins 
which  we  have  already  placed  among  the  albumins  and  globulins. 
It  is,  however,  probable  that  this  must  not  be  considered  a  prosthetic 
group,  but  is  more  intimately  united  within  the  protein  molecule. 

iii.  Nucleo-proteins. — These  are  compounds  of  protein  with  a 
complex  organic  acid  called  nucleic  acid,  which  contains  phosphorus. 
They  are  found  both  in  the  nuclei  and  cell-protoplasm  of  cells.  In 
physical  character  they  often  simulate  mucin. 

Nuclein  is  the  name  given  to  the  chief  constituent  of  cell-nuclei. 
It  is  identical  with  the  chromatin  of  histologists  (see  p.  10). 

On  decomposition  it  yields  an  organic  acid  called  nucleic  acid, 
together  with  a  variable  but  usually  small  amount  of  protein.  It 
contains  a  high  percentage  (10-11)  of  phosphorus. 

The  nuclein  obtained  from  the  nuclei  or  heads  of  the  spermatozoa 
consists  of  nucleic  acid  without  any  protein  admixture.  In  fishes' 


CH.  XXV1I1.]  THE   CONJUGATED   PROTEINS  431 

spermatozoa,  however,  there  is  an  exception  to  this  rule,  for  there  it 
is,  as  we  have  already  seen,  united  to  protamine. 

The  nucleo-proteins  of  cell  protoplasm  are  compounds  of  nucleic 
acid  with  a  much  larger  quantity  of  protein,  so  that  they  usually 
contain  only  1  per  cent,  or  less  of  phosphorus.  Some  also  contain 
iron,  and  the  normal  supply  of  iron  to  the  body  is  contained  in  the 
nucleo-proteins  or  hcematogens  (Bunge)  of  plant  or  animal  cells. 

Nucleo-proteins  may  be  prepared  from  cellular  structures  such  as  thymus, 
testis,  kidney,  etc. ,  by  two  principal  methods  : — 

1.  Wooldridges  method. — The  organ  is  minced,  and  soaked  in  water  for  twenty- 
four  hours.     Dilute  acetic  acid  added  to  the  aqueous  extract  precipitates  the  nucleo- 
protein. 

2.  Sodium  chloride  method. — The  minced  organ  is  ground  up  in  a  mortar  with 
solid  sodium  chloride ;  the  resulting  viscous  mass  is  poured  into  excess  of  water, 
and  the  nucleo-protein  rises  in  strings  to  the  top  of  the  water. 

The  solvent  usually  employed  for  a  nucleo-protein,  whichever  method  it  is 
prepared  by,  is  a  1  per  cent,  solution  of  sodium  carbonate.  The  relationship  of 
nucleo-proteins  to  the  coagulation  of  the  blood  is  described  under  that  heading. 

Nucleic  acid  yields,  among  its  decomposition  products,  phosphoric 
acid,  various  bases  of  the  purine  group,  and  bases  also  of  the 
pyrimidine  group.  A  carbohydrate  radical  is  also  obtained.  The 
following  diagrammatic  way  of  representing  the  decomposition  of 
nucleo-protein  puts  the  matter  more  clearly  : — 

NUCLEO-PROTEIN 
subjected  to  gastric  digestion  yields 


I  I 

Protein  converted  into  peptone,  Nuclein,  which  remains  as  an  insoluble 

which  goes  into  solution.  residue.     If  this  is  dissolved  in  alkali 

and  hydrochloric  acid  added,  it  yields 


Protein— converted  into  acid  A    precipitate    consisting    of    nucleic 

meta-protein  in  solution.  acid.     If  this  is  heated  in  a  sealed 

tube  with  hydrochloric  acid,  it  yields 

Phosphoric  acid.         Carbohydrate.         Purine  bases.         Pyrimidine  bases. 

Kecent   research   on   the   nucleic   acids   obtained    from   various 
mammalian  organs  indicates  that  they  fall  into  two  main  classes : — 
(1)  Nucleic  acid  proper. — This  yields  on  decomposition — 

(a)  Phosphoric  acid. 

(b)  A   sugar,   which    is    a    hexose,   but  has   not    yet    been 

identified  further ;  Levene  has  found  that  in  the  nucleic 
acids  of  vegetable  origin  (fqr  instance  from  yeast)  the 
sugar  present  is  a  pentose  (d-ribose). 

(c)  Two  members  of  the  purine  group  in  the  same  proportion 

namely,  adenine  and  guanine. 


432  THE   CHEMICAL   COMPOSITION   OF   THE   BODY      [CH.  XXVIII. 

(d)  Two  pyrimidine  bases,  namely,  cytosine  (see  p.  421),  and 

thymine  (methyl-dioxypyrimidine). 

The  purine  bases  are  specially  interesting  because  of  their  close 
relationship  to  uric  acid,  and  we  shall  have  to  deal  with  them  again 
in  our  description  of  that  substance.  They  are  all  derivatives  of  an 
atomic  complex,  named  purine  by  Fischer,  and  their  relationship  to 
each  other  is  best  seen  by  their  f ormulse : — 

Purine  C5H4N4 


fHypoxanthine  (monoxy-purine)  C5H4N40 

!  - 


Purine  baseB  Xanthine  (dioxy-purine)  C  H  N40, 


'1  Adenine  (amino-purine)  C5H3N4 . 
[Guanine  (amino-oxy-purine)  C5H3N40 .  NH2 


Uric  Acid  (trioxy-purine)  C5H4N403 

The  two  bases  obtained  from  nucleic  acid  are  the  two  which  con- 
tain the  NH2  group.  If  xanthine  and  hypoxanthine  are  obtained, 
they  are  the  secondary  effects  of  oxidative  and  de-amidising  enzymes. 

(2)  G-uanylic  acid. — This  is  a  simpler  form  of  nucleic  acid  found 
in  certain  organs  (pancreas,  liver,  etc.),  mixed  with  the  nucleic  acid 
proper.  It  yields  on  decomposition  only  three  substances,  namely: — 

(a)  Phosphoric  acid. 

(6)   A  carbohydrate  (probably  a  pentose). 

(c)    Guanine,  but  no  adenine. 

From  his  work  on  the  nucleic  acid  of  yeast,  Levene  finds  that  it  is  composed  of 
complexes  consisting  of  phosphoric  acid,  carbohydrate  (ribose),  and  a  base.  These 
are  termed  nucleotides.  Guanylic  acid,  described  above,  is  a  mono-nucleotide,  but 
the  majority  of  nucleic  acids  are  poly-nucleotides.  When  these  are  broken  down  by 
chemical  reagents,  the  first  change  is  the  removal  of  the  phosphoric  acid,  leaving 
intact  the  combinations  of  base  and  carbohydrate ;  these  latter  combinations  are 
called  nucleosides  ;  thus — 

Adenine  +  ribose  =  adenosine. 
Guanine  +  ribose  =  guanosine. 

These  nucleosides  may  be  further  split  into  base  and  ribose;  or  they  may  be 
de-amidised  (i.e.,  the  amino-group  is  removed)  and  nucleosides  obtained  in  which 
hypoxanthine  and  xanthine  are  united  with  the  ribose,  and  these  in  their  turn  may 
be  split  into  base  and  ribose. 

The  same  cleavages  are  accomplished  in  the  body  by  the  action  of  tissue- 
enzymes  contained  in  varying  degrees  in  the  different  organs  and  tissues.  As 
these  enzymes  are  specific,  the  number  which  may  come  into  successive  play  in  the 
decompositions  which  occur  in  the  body  is  very  large.  These  enzymes  are 
spoken  of  under  the  general  term  nucleases. 

Protein-hydrolysis. 

When  protein  material  is  subjected  to  hydrolysis,  as  it  is  when 
heated  with  mineral  acid,  or  superheated  steam,  or  to  the  action  of 
such  enzymes  as  pepsin  or  trypsin  in  the  alimentary  canal,  it  is 
finally  resolved  into  the  numerous  amino-acids  of  which  it  is  built. 
But  before  this  ultimate  stage  is  reached,  it  is  split  into  substances  of 
progressively  diminishing  molecular  size,  which  still  retain  many  of 


CH.  XXYIII.]  PROTEIN-HYDROLYSIS  433 

the  protein  characters.     The  products  may  be  classified  in  order  of 
formation  as  follows: — 

1.  Meta-proteins. 

2.  Proteoses. 

3.  Peptones. 

4.  Polypeptides. 

5.  Amino-acids. 

The  polypeptides  are  linkages  of  two  or  more  ammo-acids,  as 
already  explained.  Although  most  of  the  polypeptides  at  present 
known  are  products  of  laboratory  synthesis,  many  have  been 
definitely  separated  from  the  digestion  products  of  proteins.  The  pro- 
teoses,  peptones,  and  some  of  the  longer  polypeptides  give  the  biuret 
reaction  ;  the  peptones  and  polypeptides,  however,  cannot  be  salted  out 
of  solution  as  the  proteoses  can :  their  molecules  are  smaller  than  those 
of  the  proteoses.  We  shall  study  them  more  fully  under  digestion. 

It  is,  however,  convenient  to  add  here  a  brief  description  of  the 
meta-proteins.  They  are  obtained  as  the  first  stage  of  hydrolysis,  and 
also  by  the  action  of  dilute  acids  or  alkalis  on  either  albumins  or 
globulins.  The  general  properties  of  the  acid  meta-protein  and 
alkali  meta-protein  (formerly  called  acid-albumin  or  syntonin  and 
alkali-albumin),  which  are  thereby  respectively  formed,  are  as 
follows : — They  are  insoluble  in  pure  water,  but  are  soluble  in  either 
acid  or  alkali,  and  are  precipitated  by  neutralisation  unless  certain 
disturbing  influences  like  sodium  phosphate  are  present.  They  are 
precipitated  as  globulins  are  by  saturation  with  such  neutral  salts  as 
sodium  chloride  or  magnesium  sulphate.  They  are  not  coagulated  by 
heat  if  in  solution. 

The  word  albuminate  is  used  for  compounds  of  protein  with  mineral 
substances.  Thus  if  a  solution  of  copper  sulphate  is  added  to  a  solution  of 
albumin,  a  precipitate  of  copper  albuminate  is  formed.  Similarly,  by  the  addition 
of  other  salts  of  the  heavy  metals,  other  metallic  albuminates  are  obtainable.  The 
halogens  (chlorine,  bromine,  iodine)  also  form  albuminates  in  this  sense,  and  may 
be  used  for  the  precipitation  of  proteins. 

It  should  be  noted  in  conclusion  that  the  foregoing  classification  of  proteins  is 
mainly  applicable  to  those  of  animal  origin. 

There  are  certain  vegetable  proteins,  such  as  gliadin  from  the  gluten  of 
wheat,  hordein  from  barley,  and  zein  from  maize,  which  stand  apart  from  all  other 
members  of  the  group  in  being  soluble  in  alcohol. 

The  vegetable  proteins  which  have  been  mainly  studied  are  those  contained  in 
the  seeds  of  plants.  They  may  provisionally  be  grouped  into  four  main  classes  : — 

1.  Albumins,  such  as  leucosin  in  wheat. 

2.  Globulins,  such  as  edestin  of  hemp  and  other  seeds  ;  most  of  these  are  readily 
crystallisable. 

3.  Glutelins.     These  are  insoluble  in  water  and  saline  solutions,  and  are  soluble 
only  in  dilute  alkali.     They  are  probably  not  very  strongly  marked  off  from  the 
globulins,  since  it  has  been  shown  that  the  solubility  of  globulins  in  dilute  saline 
solutions  is  also  due  to  a  trace  of  alkali.     The  best  example  of  this  third  class  is  the 
glutenin  of  wheat  gluten. 

2  E 


434  THE   CHEMICAL   COMPOSITION   OF  THE  BODY      [CH.  XXVIII. 

4.  Gliadins  ;  the  proteins  soluble  in  alcohol  just  alluded  to.  They  are  character- 
ised also  by  the  absence  of  lysine  among  their  cleavage  products,  and  usually  yield 
a  very  high  percentage  of  glutamic  acid  on  decomposition.  The  gluten  of  wheat 
flour,  which  is  formed  when  water  is  added  to  it,  has  been  shown  to  consist  of  two 
proteins — one  (gliadin)  soluble  in  alcohol,  the  other  (glutenin)  soluble  in  alkali.  It 
is  to  the  former  that  the  gluten  of  dough  owns  its  cohesiveness  ;  and  grains  such  as 
rice,  which  contain  no  gliadin,  cannot  in  consequence  be  employed  for  making 
bread. 

The  Polarimeter. 

This  instrument  is  one  by  means  of  which  the  action  of  various  substances  on 
the  plane  of  polarised  light  can  be  observed  and  measured.  Most  of  the  carbo- 
hydrates are  dextro-rotatory.  All  the  proteins  are  laevo-rotatory  (see  p.  425). 

There  are  many  varieties  of  the  instrument ;  these  can  only  be  properly  studied 
in  the  laboratory,  and  all  one  can  do  here  is  to  state  briefly  the  principles  on 
which  they  are  constructed. 

Suppose  one  is  shooting  arrows  at  a  fence  made  up  of  narrow  vertical  palings  ; 
suppose  also  that  the  arrows  are  flat  like  the  laths  of  a  Venetian  blind.  If  the 
arrows  are  shot  vertically  they  will  pass  easily  through  the  gaps  between  the 
palings,  but  if  they  are  shot  horizontally  they  will  be  unable  to  pass  through  at 
all.  This  rough  illustration  will  help  us  in  understanding  what  is  meant  by  polarised 
light.  Ordinary  light  is  produced  by  the  undulations  of  the  aether  occurring  in  all 
directions  at  right  angles  to  the  path  of  propagation  of  the  wave.  Polarised  light 
is  produced  by  undulations  in  one  plane  only;  we  may  compare  it  to  our  flat 
arrows. 

In  a  polarimeter,  there  is  at  one  end  of  the  instrument  a  Nicol's  prism,  which 
is  made  of  Iceland  spar.  This  polarises  the  light  which  passes  through  it ;  it  is 
called  the  polariser.  At  the  other  end  of  the  instrument  is  another  called  the 
analyser.  Between  the  two  is  a  tube  which  can  be  filled  with  fluid.  If  the  analyser 
is  parallel  to  the  polariser  the  light  will  pass  through  to  the  eye  of  the  observer. 
But  if  the  analyser  is  at  right  angles  to  the  polariser  it  is  like  the  flat  arrows  hitting 
horizontally  the  vertical  palings  of  the  fence,  and  there  is  darkness.  At  inter- 
mediate angles  there  will  be  intermediate  degrees  of  illumination. 

If  the  analyser  and  polariser  are  parallel  and  the  intermediate  tube  filled  with 
water,  the  light  will  pass  as  usual,  because  water  has  no  action  on  the  plane  of 
polarised  light.  But  if  the  water  contains  sugar  or  some  **  optically  active  "  substance 
in  solution,  the  plane  is  twisted  in  one  direction  or  the  other  according  as  the  sub- 
stance is  dextro-  or  laevo-rotatory.  The  amount  of  rotation  is  measured  by  the 
number  of  angles  through  which  the  analyser  has  to  be  turned  in  order  to  obtain 
the  full  illumination.  This  will  vary  with  the  length  of  the  tube  and  the  strength 
of  the  solution. 

The  Lipoids. 

This  name  was  first  applied  by  Overton  to  a  heterogeneous  group 
of  substances  found  in  the  protoplasm  of  all  cells,  especially  in  their 
outer  layer  or  cell-membrane,  which,  like  the  fats,  are  soluble  in  such 
reagents  as  ether  and  alcohol.  These  substances,  though  present  in 
smaller  amount  than  proteins,  appear  to  be  essential  constituents  of 
protoplasm,  and  the  labile  character  of  their  molecules  is  a  property 
many  of  them  share  in  common  with  the  proteins. 

The  lipoids  are  found  mixed  with  fat  in  the  ether-alcohol 
extract  of  tissues  and  organs,  and  they  are  specially  abundant  in 
nervous  tissues.  They  can  be  separated  by  what  is  called  selective 
extraction.  For  instance,  cold  acetone  will  dissolve  out  only  choles- 
terin ;  hot  acetone  then  dissolves  out  a  mixture  of  substances  named 


CH.  XXVIII.]  CHOLESTERIN  435 

protagon ;  protagon  may  be  separated  into  its  constituents  (phrenosin 
and  sphingomyelin)  by  pyridine,  and  so  forth. 

The  lipoids  may  be  classified  in  the  following  way : — 

(1)  Those  which,  like  the  fats,  are  free  from  both  nitrogen  and  phos- 
phorus.    The  most  important  member  of  this  group  is  cholesterin. 

(2)  Those  which  are  free  from  phosphorus  but  contain  nitrogen. 
These  yield  the  reducing  sugar  called  galactose  when  broken  up,  and 
may,  therefore,  be  called  galactosides. 

(3)  Those  which  contain  both  phosphorus  and  nitrogen.     These 
are  called  the  phosphatides,  and  are  grouped  according  to  the  propor- 
tion of  nitrogen  and  phosphorus  in  their  molecules,  as  follows : — 

(a)  Mono  -  amino  -  mono  -  phosphatides,  N  :  P  =  1 : 1.  E.g., 
lecithin  and  kephalin. 

(&)  Diamino-mono-phosphatides,  N  :  P  =  2  : 1.  E.g.,  sphingo- 
myelin. 

(c)  Mono-amino-diphosphatides,  N  :  P  =  1 :  2.      One  of  these, 

named  cuorin,  hr  s  been  separated  out  from  the  heart  by 
Erlandsen,  and  a  similar  substance  is  found  in  egg-yolk. 

(d)  Diamino-diphosphatides,  N  :  P  =  2  :  2.     One  of  these  was 

separated  from  brain  by  Thudichum,  but  has  not  since 
been  examined. 

(e)  Triamino-mono -phosphatides,  N:  P  =  3  : 1.      One  of  these 

is  present  in  egg-yolk. 

Cholesterin  or  cholesterol  is  found  in  small  quantities  in  all 
forms  of  protoplasm.  It  is  a  specially  abundant  constituent  of 
nervous  tissues,  particularly  in  the  white  substance  of  Schwann. 
It  is  found  in  small  quantities  in  the  bile,  but  it  may  occur  there  in 
excess  and  form  the  concretions  known  as  gall-stones.  It  can  be 
readily  extracted  from  the  brain  by  the  use  of  cold  acetone.  In  the 
brain  it  occurs  in  the  free  state. 

It  is  a  monatomic  unsaturated  alcohol  with  the  empirical  formula 
C27H45 .  OH.  Eecent  research  has  shown  it  to  belong  to  the  terpene 
series,  which  had  hitherto  only  been  found  as  excretory  products  of 
plant  life.  Windaus  has  shown  that  it  contains  five  reduced  benzene 
rings  linked  together,  with  a  double  linkage  at  the  end  of  an  open  chain. 

Cholesterin  is  now  believed  to  be  not  merely  a  waste  product  of 
metabolism,  but  to  exert  an  important  protective  influence  on  the 
body  cells  against  the  entrance  of  certain  poisons  called  toxins. 
One  of  the  poisons  contained  in  cobra  venom  dissolves  red  blood- 
corpuscles  ;  the  presence  of  cholesterin  in  the  envelope  of  the 
blood-corpuscles  to  some  extent  hinders  this  action,  and  it  has 
been  stated  that  the  administration  of  cholesterin  increases  the 
resistance  of  the  animal.  It  is  certainly  the  case  that  with  arti- 
ficial blood-corpuscles,  membranous  bags  containing  haemoglobin, 


436 


THE   CHEMICAL  COMPOSITION   OF  THE   BODY      [CH.  XXV11I. 


FIG.  315.—  Cholesterin  crystals. 


the   impregnation  of  the  membrane  with  cholesterin,  prevents  the 

solvent  action  of  toxins. 

In  order  that  cholesterin  and  its  derivatives  may  act  in  this  way,  it 

is  necessary  that  the  double  linkage  and 
the  hydroxyl  atom  just  referred  to 
should  be  intact.  The  latter  would 
not  be  the  case  in  an  ester,  and  it  is 
probable  that  the  compounds  of  choles- 
terin in  the  blood  previously  described 
as  esters  by  Hiirthle  are  really  mixtures 
of  cholesterin  and  fatty  acids. 

From  alcohol  or  ether  containing 
water  it  crystallises  in  the  form  of  rhom- 
bic tables,  which  contain  one  molecule  of 
water  of  crystallisation :  these  are  easily 
recognised  under  the  microscope  (fig.  315). 
It  gives  the  following  colour  tests : — 

1.  Heated  with  sulphuric  acid  and  water  (5:1),  the  edges  of  the 
crystals  turn  red. 

2.  A  solution  of  cholesterin  in  chloroform,  shaken  with  an  equal 
amount  of  strong   sulphuric  acid,  turns   red,  and  then  purple,  the 
subjacent  acid  acquiring  a  green  fluorescence.    (Salkowski's  reaction.) 

3.  If  acetic  anhydride  is   added   to  a  chloroformic  solution  of 
cholesterin,  and  then  sulphuric  acid,  drop  by  drop,  a  red  coloration, 
which  changes  to  bluish  green,  is  produced.    (Liebermann's  reaction.) 

A  substance  called  iso-cholesterin  is  found  in  the  fatty  secretion 
of  the  skin  (sebum) ;  it  is  largely  contained  in  the  preparation  called 
lanoline,  made  from  sheep's  wool  fat.  It  differs  from  cholesterin  in 
being  dextro-rotatory  instead  of  Isevo-rotatory  in  solution,  and  it 
does  not  give  Salkowski's  colour  reaction.  Cholesterins  isomeric  with 
animal  cholesterin  are  also  found  in  many  plants ;  these  are  termed 
phyto-cholesterins,  or  phytosterins  for  short. 

Cholesterin  compounds  exhibit  the  physical  phenomenon  recently 
studied  by  Lehmann,  namely,  the  formation  of  liquid  crystals ; 
this  is  also  shown  by  several  other  lipoids.  Virchow  in  1855 
described  what  he  termed  "  myelin  forms " ;  if  brain-substance 
is  mixed  with  water,  where  the  water  touches  the  brain  material, 
threads  are  observable  shooting  out  and  twisting  into  fantastic 
shapes ;  these  are  termed  "  myelin  forms/'  although  the  word  myelin 
has  no  definite  chemical  meaning.  It  has  now  been  shown  that  these 
"  myelin  forms "  are  distorted  liquid  crystals  due  to  the  presence  of 
cholesterin  and  other  lipoids.  The  fat  globules  seen  in  the  adrenal 
cortex,  and  in  the  liver  and  other  organs  during  fatty  degeneration, 
are  not  wholly  composed  of  fat,  for  the  polarisation  microscope  shows 
them  to  be  anisotropic,  and  further  investigation  has  shown  them  to 


CH.  XXYIII.]  CHOLESTERIN  437 

be  lipoids  in  the  fluid  crystalline  condition.  Pure  cholesterin  and 
pure  cholesterin  esters  do  not  exhibit  the  phenomenon ;  but  mixtures 
of  cholesterin  and  fatty  acids  do;  it  has  been  suggested  that  in 
such  mixtures  the  acid  is  incorporated  as  "acid  of  crystallisation," 
analogous  to  the  "  water  of  crystallisation  "  in  many  other  crystals. 

The  Galactosides. — The  substance  known  as  protagon  can  be 
separated  out  from  the  brain  by  means  of  warm  alcohol ;  on  cooling 
the  extract,  protagon  is  deposited  as  a  white  precipitate.  This,  how- 
ever, also  contains  cholesterin,  which  can  be  dissolved  out  by  ether. 
Another  method  of  preparing  protagon  is  to  take  brain  and  extract 
the  cholesterin  first  with  cold  acetone ;  then  hot  acetone  is  employed 
to  extract  the  protagon.  Protagon  is  a  substance  originally  described 
by  Couerbe,  under  the  name  cerebrote,  but  named  protagon  by 
Liebreich,  who  regarded  it  as  a  definite  compound,  and  the  mother 
substance  of  all  the  other  phosphorised  and  non-phosphorised  con- 
stituents of  the  brain.  It  has  now  been  definitely  proved  in  confir- 
mation of  what  Thudichum  stated  in  1874,  that  protagon  is  not 
important  quantitatively,  and  is  not  a  definite  chemical  unit,  but  a 
mixture  of  phosphorised  and  non-phosphorised  substances  in  such 
proportions  that  it  usually  contains  about  1  per  cent,  of  phosphorus. 
By  treatment  with  appropriate  reagents  and  recrystalhsation,  pro- 
tagon can  be  separated  into  its  constituents,  and  those  which  are  free 
from  phosphorus  and  comprise  about  70  per  cent,  of  the  original 
protagon  are  the  galactosides.  The  known  galactosides  are  two  in 
number,  namely,  phrenosin  (or  cerebron)  and  kerasin.  The  former 
is  a  crystalline  product,  and  the  latter  of  somewhat  waxy  con- 
sistency. They  are  probably  isomerides.  They  yield  on  decomposi- 
tion three  substances : — (1)  A  reducing  sugar,  galactose.  (2)  A  base 
termed  sphingosine,  about  which  little  chemically  is  yet  known. 
(3)  A  fatty  acid  of  high  molecular  weight,  termed  neuro-stearic 
acid  by  Thudichum,  but  not  definitely  identified.  It  is  probably  an 
oxy-acid  (Thierfelder). 

The  Phosphatides. — The  best  known  of  these  is  lecithin. 
This  is  a  very  labile  substance,  but  it  yields  on  decomposition  four 
materials,  namely — glycerin  and  phosphoric  acid  united  together  as 
glycero-phosphoric  acid,  two  fatty  acid  radicals,  of  which  one  is 
usually  oleic  acid,  and  an  ammonium-like  base  termed  choline.  The 
fatty  acid  radicals  are  united  to  glycerin  as  in  an  ordinary  fat,  the 
place  of  the  third  fatty  acid  being  taken  by  the  radical  of  phosphoric 
acid,  which  in  its  turn  is  united  in  an  ester-like  manner  to  the 
choline.  The  clinical  significance  of  such  substances  in  cases  of 
degenerative  nervous  disease  has  been  already  alluded  to  on  p.  167. 

Kephalin  resembles  lecithin  in  being  a  mono-amino-monophos- 
phatide.  It  differs  from  lecithin  in  being  insoluble  in  alcohol.  On 
decomposition  it  yields  glycero-phosphoric  acid,  certain  fatty  acids 


438  THE  CHEMICAL  COMPOSITION   OF  THE   BODY      [CH.  XXVIII. 

which  are  less  saturated  than  oleic  acid,  and  probably  belong  to  the 
linoleic  series.  It  also  yields  a  base,  but  it  is  doubtful  if  this  is 
identical  with  choline.  Kephalin  is  the  most  abundant  phosphatide 
in  nerve-fibres,  and  has  also  been  found  in  egg-yolk. 

Sphingomyelin  is  the  phosphatide  obtained  from  the  mixture 
called  protagon.  It  is  the  best  known  of  the  diamino-monophos- 
phatides.  If  protagon  is  dissolved  in  hot  pyridine,  and  the  solution 
allowed  to  cool,  sphingomyelin  is  precipitated  in  an  impure  form  as 
sphaero-crystals,  which  rotate  the  plane  of  polarised  light  to  the  left. 
Choline,  fatty  acids,  and  an  alcohol  have  been  found  among  its  cleav- 
age products.  It,  however,  differs  from  lecithin  by  containing  no 
glycerin. 

Enzymes. 

The  word  fermentation  was  first  applied  to  the  change  of  sugar 
into  alcohol  and  carbonic  acid  by  means  of  yeast.  The  evolution  of 
carbonic  acid  causes  frothing  and  bubbling ;  hence  the  term  "  fermen- 
tation." The  agent,  yeast,  which  produces  this,  was  called  the  ferment. 
Microscopic  investigation  shows  that  yeast  is  composed  of  minute 
rapidly-growing  unicellular  organisms  belonging  to  the  fungus  group. 

The  souring  of  milk,  the  transformation  of  urea  into  ammonium 
carbonate  in  decomposing  urine,  and  the  formation  of  vinegar  from 
alcohol  are  brought  about  by  very  similar  organisms.  The  complex 
changes  known  as  putrefaction,  which  are  produced  by  the  various 
forms  of  bacteria  (see  fig.  316),  also  come  into  the  same  category. 

That  the  change  or  fermentation  is  produced  by  these  organisms 
is  shown  by  the  fact  that  it  occurs  only  when  the  organisms  are 
present,  and  stops  when  they  are  removed  or  killed  by  a  high 
temperature  or  by  antiseptics  (carbolic  acid,  etc). 

The  "germ  theory"  of  disease  explains  the  infectious  diseases  by 
considering  that  the  change  in  the  system  is  of  the  nature  of  fermen- 
tation, and,  like  the  others  we  have  mentioned,  produced  by  microbes ; 
the  transference  of  the  bacteria  or  their  spores  from  one  person  to 
another  constitutes  infection.  The  poisons  produced  by  the  growing 
bacteria  appear  to  be  either  alkaloid al  (ptomaines)  or  protein  in 
nature.  The  most  virulent  poison  in  existence,  namely,  snake  poison, 
is  a  protein  of  the  proteose  class. 

All  these  micro-organisms  require  moisture  in  which  to  act. 
They  act  best  at  a  temperature  of  about  40°  C.  Their  activity  is 
stopped,  but  the  organisms  are  not  destroyed  by  cold.  The  organisms 
are,  however,  like  other  living  cells,  killed  by  too  great  heat.  Some 
micro-organisms  act  without  free  oxygen;  these  are  called  anaerobic ; 
those  that  require  oxygen  are  called  aerobic. 

Another  well-known  fact  concerning  micro-organisms  is  that  the 
substances  they  produce  in  time  put  a  stop  to  their  activity ;  thus 


CH.  XXVIII.] 


ENZYMES 


439 


in  the  case  of  yeast,  the  alcohol  produced,  and  in  the  case  of 
bacteria  acting  on  proteins,  the  phenol,  cresol,  etc.,  produced,  first 
stop  the  growth  of,  and  ultimately  kill,  these  organisms. 

For  a  long  time  it  was  uncertain  how  micro-organisms  were  able 


°°boo°' 


00° 


7 


FIG.  316.— Types  of  micro-organisms  :  a,  micrococci  arranged  singly ;  in  twos,  diplococci— if  all  the 
micrococci  at  a  were  grouped  together  they  would  be  called  staphylococci — and  in  fours,  sarcinse  ; 
b,  micrococci  in  chains,  streptococci ;  c  and  d,  bacilli  of  various  kinds  (one  is  represented  with 
a  flagellum) ;  e,  various  forms  of  spirilla ;  /,  spores,  either  free  or  in  bacilli. 

to  effect  these  chemical  transformations.  It  is  now,  however, 
definitely  proved  that  they  do  so  by  producing  agents  of  a  chemical 
nature,  which  are  called  enzymes.  This  was  first  demonstrated  in 
connection  with  the  invertase  of  yeast  cells,  and  with  the  enzyme 
secreted  by  the  micrococcus  urese,  which  converts  urea  into  ammonium 
carbonate  in  putrefying  urine.  For  a  long  time,  however,  efforts 
to  obtain  from  yeast  cells  an  enzyme  capable  of  bringing  about  the 
alcoholic  fermentation  were  unsuccessful.  This  is  because  the 
enzyme  does  not  leave  the  yeast  cells,  but  acts  intracellularly. 
Buchner,  by  crushing  the  yeast  cells,  succeeded  in  obtaining  from 
them  the  long-sought  enzyme  (zymase)  ;  since  then  other  enzymes 
have  been  obtained  from  other  microbes  by  similar  means. 

Enzymes  are  also  formed  by  the  cells  of  the  higher  organisms, 
both  in  animal  and  vegetable  life.  Familiar  instances  of  these  are 
ptyalin,  the  starch-splitting  enzyme  of  saliva,  and  pepsin,  the 
protein-splitting  enzyme  of  gastric  juice.  The  substance  upon 
which  the  enzyme  acts  is  spoken  of  as  the  substrate. 

We  may,  therefore,  place  these  essential  facts  concerning  enzyme 
action  in  the  following  tabular  way : — 


The  Living  Cell. 

The  Enzyme 
produced. 

The  Substrate. 

The  Products  of  Action. 

The  yeast  cell  . 
The  salivary  cell 
The  gastric  cell 

Zymase  . 
Ptyalin   . 
Pepsin    . 

Dextrose   . 
Cooked  starch  . 
Protein      . 

Alcohol   and    carbon 
dioxide. 
Dextrin     and      mal- 
tose. 
Proteoses,   peptones, 
and  amino-acids. 

440  THE   CHEMICAL  COMPOSITION   OF  THE   BODY      [CH.  XXVIII. 

The  enzymes  which  bring  about  the  digestion  of  food  in  the 
alimentary  canal  may  be  classified  as  follows : — 

1.  Amylolytic — -those    which    convert    polysaccharides   (starch, 
glycogen)  into  sugar  with  intermediate  dextrins.     Examples:    the 
diastase  of  vegetable  seeds,  and  the  ptyalin  of  saliva. 

2.  Inverting — those   which   convert    disaccharides    into   mono- 
saccharides.       Examples :    Invertase    of    yeast   cells ;    invertase    of 
intestinal  juice ;    these   convert  cane   sugar    into    equal   parts   of 
dextrose  and  laevulose. 

3.  Lipolytic — those    which    split    fat    into    fatty    acids    and 
glycerin.     An  example,  lipase,  is  found  in  pancreatic  juice. 

4.  Proteolytic  or  proteoclastic — those  which  split  proteins  into 
proteoses,  peptones,  polypeptides,  and  finally  amino-acids.    Examples: 
the  pepsin  of  gastric,  and  the  trypsin  of  pancreatic  juice. 

5.  Peptolytic — those  which  split  proteoses  and  peptones   into 
polypeptides  and  amino-acids,  e.g.,  the  erepsin  of  intestinal  juice. 

But  in  addition  to  the  digestive  enzymes  there  are  others  to  be 
mentioned,  for  instance : — 

The  enzymes  in  the  foregoing  list  produce  hydrolysis;  that  is, 
water  is  added  to  the  substrate,  which  then  splits  into  simpler 
molecules,  as  for  instance  in  the  inversion  of  cane  sugar  by  invertase. 

C12H22On   +   H20   =   C6H1206   +   C6H1206. 

[Cane  sugar.]  [Water.]  [Dextrose.]  [Laevulose.] 

Coagulative  enzymes  —  those  which  convert  soluble  into 
insoluble  proteins;  the  best  example  of  this  class  is  thrombin  or 
fibrin-ferment,  which  comes  into  play  in  blood-coagulation,  convert- 
ing the  soluble  protein  in  blood -plasma  called  fibrinogen  into  fibrin. 
Eennet  or  rennin,  found  in  the  gastric  juice,  is  another ;  it  converts 
the  soluble  caseinogenate  of  milk  into  casein. 

Oxidases ;  these  are  not  hydroly tic,  but  are  oxygen  carriers  and 
produce  oxidation :  they  are  mainly  found  as  intracellular  enzymes, 
and  are  important  in  tissue  respiration. 

Reductases;  these  are  the  counterpart  of  the  oxidases,  and 
produce  reduction  in  the  tissues. 

Deamidases ;  these  remove  the  ammo-group  from  amino- 
compounds. 

Intracellular  or  Autolytic  Enzymes. — These  come  into  play 
during  cell  life,  and  are  important  in  the  metabolic  or  intracellular 
chemical  changes  which  occur  in  protoplasm;  they  also  may  be 
subdivided  into  proteolytic,  peptolytic,  lipolytic,  etc.,  according  to 
the  substrate  upon  which  they  act.  After  death  their  activity 
continues,  and  so  they  produce  self-digestion  or  autolysis  of  the 
cells  in  which  they  are  situated,  if  the  tissue  or  organ  is  kept  at 
an  appropriate  temperature  and  under  aseptic  conditions. 


CH.  XXVIH.]  CLASSIFICATION   OF   ENZYMES  441 

The  foregoing  list  is  not  by  any  means  complete,  but  includes  the 
most  important  groups.  The  individual  enzymes  will  be  studied  in 
due  course,  but  for  the  present  we  will  take  general  considerations 
only. 

Zymogens. — These  are  the  parent  substances  or  precursors  of  the 
enzymes.  The  granules  seen  in  many  secreting  cells  consist  very 
largely  of  zymogen,  which  in  the  act  of  secretion  is  converted  into 
the  active  enzyme.  Thus,  pepsin  is  formed  from  pepsinogen,  trypsin 
from  trypsinogen,  thrombin  from  thrombogen,  and  so  forth. 

Activation  of  Enzymes.  Co-enzymes. — Many  enzymes  contained 
in  secretions  are  in  a  condition  ready  for  action.  In  other  cases 
this  is  not  so,  and  their  action  only  occurs  after  they  have  been 
rendered  energetic  by  the  presence  or  action  of  other  substances, 
termed  activating  agents  or  co-enzymes. 

The  Specificity  of  Enzyme  Action. — In  most  cases  the  action  of 
an  enzyme  is  extraordinarily  limited ;  thus  there  are  three  separate 
enzymes  to  hydrolyse  the  three  principal  disaccharides,  cane  sugar, 
lactose,  and  maltose,  neither  of  which  will  act  upon  either  of  the 
other  two  sugars  in  the  list.  Arginase  splits  arginine  into  orni thine 
and  urea,  but  will  act  upon  no  other  substance.  The  "lock  and 
key "  simile  first  introduced  by  Emil  Fischer  will  aid  us  in  under- 
standing this  specificity  of  action.  Each  lock  must  have  its  special 
key:  so  the  chemical  configuration  of  an  enzyme  must  be  related 
in  some  way  to  the  configuration  of  the  substrate  to  enable  it  to 
enter  and  unlock  its  parts  from  one  another. 

The  Optimum  Temperature  of  Enzyme  Action. — As  the  tempera- 
ture rises  the  velocity  of  the  action  increases,  until  a  temperature 
is  reached  at  which  the  activity  is  greatest.  Most  enzymes  act 
best  at  40°  C.,  but  there  are  exceptions ;  malt  diastase,  for  instance, 
acts  best  at  60°  C.  Beyond  the  optimum  temperature  a  further  rise 
inhibits  activity,  until  a  temperature  is  reached  when  the  enzyme 
is  destroyed.  The  fatal  temperature  as  a  rule  is  in  the  neighbour- 
hood of  50°  C. 

The  effect  of  a  rise  of  temperature  is  thus  complex,  and  is  of 
a  two-fold  nature.  In  the  first  place,  and  between  certain  limits, 
the  law  of  Arrhenius  is  followed,  that  is,  a  rise  of  10°  doubles  or 
even  trebles  the  velocity  of  the  action  of  the  enzyme,  as  it  does 
other  chemical  reactions.  But  as  the  temperature  rises  the  velocity 
of  disintegration  of  the  enzyme  also  rises.  The  optimum  tempera- 
ture is  that  at  which  the  enzyme  work  is  best  done;  this  is  a 
temperature  at  which  the  accelerating  effect  is  strong  enough  to  finish 
the  reaction  quickly,  and  the  retarding  effect  due  to  enzyme  destruc- 
tion is  not  so  great  as  to  neutralise  the  accelerating  effect. 

The  Inexhaustibility  of  Enzymes. — A  small  amount  of  enzyme 
will  act  on  an  unlimited  amount  of  substrate,  provided  sufficient 


442  THE   CHEMICAL   COMPOSITION   OF   THE   BODY      [CH.  XXVIII. 

time  is  given,  and  provided  also  the  products  of  action  are  removed. 
The  enzyme  appears  to  take  a  share  in  intermediate  reactions,  and 
there  is  some  evidence  that  in  certain  stages  it  combines  with  the 
substrate;  but  subsequently  when  the  substrate  breaks  up  into 
simpler  materials,  the  enzyme  is  liberated  unchanged,  and  so  ready 
to  similarly  act  on  a  fresh  amount  of  substrate. 

Catalytic  Action  of  Enzymes. — The  analogy  of  enzymic  action  is, 
in  fact,  so  close  to  that  of  inorganic  catalysts,  that  the  view  at 
present  current  regarding  it  is  that  the  action  is  a  catalytic  one. 
That  is  to  say,  the  presence  of  the  enzyme  induces  a  chemical 
reaction  to  occur  rapidly,  which  in  its  absence  also  occurs,  but  so 
slowly  that  any  action  at  all  is  difficult  to  discover.  To  use  the 
technical  phrase,  its  action  is  to  increase  the  velocity  of  chemical 
reactions.  It  is,  for  instance,  quite  conceivable  that,  if  starch  and 
water  were  mixed  together,  the  starch  will  in  time  take  up  the 
water  and  split  into  its  constituent  molecules  of  sugar.  But  an 
action  of  this  kind  would  be  so  slow,  occupying  perchance  many 
years,  that  for  practical  purposes  it  does  not  take  place  at  all.  If 
an  inorganic  catalyst  is  added,  such  as  sulphuric  acid,  and  the 
temperature  raised  to  boiling  point,  the  action  takes  place  in  a  few 
minutes;  if  an  organic  catalyst,  such  as  the  enzyme  ptyalin,  is 
added,  the  velocity  of  the  change  is  even  greater ;  but  what  is  of 
more  importance  for  the  well-being  of  the  animal,  a  moderate 
temperature,  namely  that  of  the  body,  amply  suffices.  The  organic 
catalysts  or  enzymes  are,  however,  colloidal  in  nature  (possibly  pro- 
tein), and  this  explains  their  destructibility  by  high  temperatures. 

Reversibility  of  Enzyme  Action. — On  page  329  we  have  considered 
the  general  laws  of  molecular  reactions.  The  majority  of  enzymatic 
reactions  are  unimolecular,  or  reactions  of  the  first  order ;  that  is  to 
say,  one  substance  only,  the  substrate,  undergoes  transformation ; 
the  other  substance,  the  enzyme,  does  not  alter  in  concentration. 
The  law  followed  in  such  reactions  is  therefore  the  simple  logarithmic 
law.  But  in  these  reactions  we  meet  with  the  peculiarity  that 
it  is  not  quite  completed  when  the  reaction  ceases.  A  certain 
quantity  of  the  substrate  never  disappears.  Thus  a  small  amount  of 
cane  sugar  remains  unchanged  whether  the  hydrolysis  is  brought 
about  by  the  action  of  an  acid  or  of  an  enzyme.  This  phenomenon 
is  due  to  the  fact  that  two  reactions  are  always  taking  place  in 
opposite  directions.  Simultaneously  with  the  splitting  up  the 
synthetical  reaction  begins,  and  synthesis  or  building  up  increases  in 
proportion  as  the  splitting  of  the  compound  advances.  The  velocity 
of  the  splitting  process  decreases  at  the  same  rate  as  the  velocity  of 
the  synthetic  process  increases.  At  a  certain  point,  both  have  the 
same  velocity,  and  therefore  no  further  change  occurs  in  the  mixture 
when  this  condition  of  equilibrium  is  reached.  This  rule  is  expressed 


CH.  XXVIII.]  ACTION   OF  ENZYMES  443 

by  writing  the  chemical  equation  connected  by  a  double  arrow 
instead  of  the  sign  of  equation.  Two  examples  follow  : — 

C2Hfi .  OH  +  CH3 .  COOH  ^_±  C2H5 .  COO  .  CH3  +  H2O 

[Ethyl  alcohol.]  [Acetic  acid.]  [Ethyl  acetate.]  [Water.] 

C6H1206  +  CCH1206  ^±  C12H22On  +  H20 

[Dextrose.]  [Laevulose.]  [Cane  sugar.]        [Water.] 

This  phenomenon  is  termed  "reversibility,"  and  was  first  demon- 
strated by  Croft  Hill  in  his  experiments  with  cane  sugar  and 
invertase. 

In  intracellular  action  this  is  a  factor  of  importance,  for  the 
same  enzyme  can  in  the  presence  of  different  proportions  of  the 
substrate  and  its  cleavage  products  both  tie  (in  anabolism)  and 
untie  (in  katabolism)  the  knot. 

It  should  further  be  noted  that  hydrolytic  actions  are  isothermic ; 
that  is,  the  total  energy  of  the  products  is  equal  to  that  of  the 
substance  broken  up. 

The  simpler  logarithmic  law  of  enzyme  action  has  been  demon- 
strated for  the  majority  of  enzymes  (invertase,  trypsin,  erepsin, 
lipase,  etc.).  The  effect  in  a  given  time  is  directly  proportional  to 
the  quantity  of  enzyme  present.  But  there  is  an  exception  to  this 
rule  in  the  case  of  pepsin,  as  was  first  pointed  out  by  Schutz  in  1885. 
He  found  that  peptic  activity  is  proportional  to  the  square  root  of 
the  amount  of  pepsin  present.  Thus  if  a  certain  quantity  of  pepsin 
produced  an  amount  of  digestive  action  which  we  will  call  a,  in 
order  to  produce  a  digestive  action  equal  to  2a  in  the  same  time,  it 
would  be  necessary  to  employ  four  times  the  amount  of  pepsin  ;  and 
in  order  to  produce  a  digestive  action  equal  to  3a,  it  would  be 
necessary  to  use  nine  times  the  amount  of  pepsin.  This  rule 
(Schiitz's  law)  has  been  often  confirmed,  and  a  few  years  ago 
Arrhenius  explained  it  on  mathematical  lines  into  which  we  need  not 
enter  here. 

Anti-enzymes. — Many  chemical  substances,  such  as  strong  acids 
and  alkalis,  alcohol,  formaldehyde,  iodine,  potassium  cyanide,  and 
salts  of  the  heavy  metals,  hinder  enzyme  activity.  But  the  term 
anti-enzyme  is  generally  limited  to  substances  produced  in  the 
metabolism  of  living  organisms.  Excess  of  these  organic  anti- 
enzymes  can  be  readily  produced  by  injecting  an  enzyme  into  the 
blood-stream  of  an  animal.  This  stimulates  the  production  of  an 
anti-enzyme,  so  that  when  the  blood-serum  is  mixed  with  the  original 
enzyme,  its  power  is  inhibited.  Anti-enzymes  are  specific,  that  is, 
they  inhibit  the  enzyme  which  was  injected  into  the  blood,  and  no 
other. 


CHAPTER   XXIX 

THE   BLOOD 

THE  blood  is  the  fluid  medium  by  means  of  which  all  the  tissues  of 
the  body  are  directly  or  indirectly  nourished ;  by  means  of  it  also 
such  of  the  materials  resulting  from  the  metabolism  of  the  tissues 
which  are  of  no  further  use  in  the  economy  are  carried  to  the  excre- 
tory organs.  It  is  a  somewhat  viscid  fluid,  and  in  man  and  in  all 
other  vertebrate  animals,  with  the  exception  of  two,*  is  red  in  colour. 
It  consists  of  a  yellowish  fluid,  called  plasma  or  liquor  sanguinis, 
in  which  are  suspended  numerous  blood-corpuscles,  the  majority  of 
which  are  coloured,  and  it  is  to  their  presence  that  the  red  colour  of 
the  blood  is  due.  In  addition  to  the  red  corpuscles,  there  are  a 
smaller  number  of  colourless  corpuscles,  and  some  extremely  small 
particles  called  blood-platelets. 

Even  when  examined  in  very  thin  layers,  blood  is  opaque,  on 
account  of  the  different  refractive  powers  possessed  by  its  two 
constituents,  the  plasma  and  the  corpuscles.  On  treatment  with 
ether,  water,  and  other  reagents,  however,  it  becomes  transparent  and 
assumes  a  lake  colour,  in  consequence  of  the  colouring  matter  of  the 
corpuscles  having  been  discharged  into  the  plasma.  The  average 
specific  gravity  of  blood  at  15°  C.  (60°  F.)  varies  from  1055  to  1062. 
A  rapid  and  useful  method  of  estimating  the  specific  gravity  of  blood 
was  invented  by  Roy.  Drops  of  blood  are  taken  and  allowed  to  fall 
into  fluids  of  known  specific  gravity.  When  the  drop  neither  rises 
nor  sinks  in  the  fluid  it  is  taken  to  be  of  the  same  specific  gravity  as 
that  of  the  standard  fluid.  The  reaction  of  blood  is  faintly  alkaline  to 
litmus  and  the  taste  saltish.  Its  temperature  varies  slightly,  the  average 
being  37'8°  C.  (100°  F.).  The  blood-stream  is  warmed  by  passing 
through  the  muscles,  and  glands,  but  is  somewhat  cooled  on 
traversing  the  capillaries  of  the  skin.  Recently  drawn  blood  has  a 
distinct  odour,  which  in  many  cases  is  characteristic  of  the  animal 
from  which  it  has  been  taken ;  it  may  be  further  developed  by  adding 
to  blood  a  mixture  of  equal  parts  of  sulphuric  acid  and  water. 

Quantity  of  the  Blood. — The  quantity  of  blood  in  an  animal 
is  usually  estimated  in  the  following  manner: — A  small  quantity 

*  The  ampliioxus  and  the  leptocoplialus. 


CH.  XXIX.]  THE   BLOOD  445 

of  blood  is  fcakeu  from  an  animal  by  venesection ;  it  is  defibrinated 
and  measured,  and  used  to  make  standard  solutions  of  blood.  The 
animal  is  then  rapidly  bled  to  death,  and  the  blood  which  escapes  is 
collected.  The  blood-vessels  are  next  washed  out  with  saline  solu- 
tion until  the  washings  are  no  longer  coloured,  and  these  are  added 
to  the  previously  withdrawn  blood  ;  lastly,  the  whole  animal  is  finely 
minced  with  saline  solution.  The  fluid  obtained  from  the  mincings 
is  carefully  filtered  and  added  to  the  diluted  blood  previously  obtained, 
and  the  whole  is  measured.  The  next  step  in  the  process  is  the  com- 
parison of  the  colour  of  the  diluted  blood  with  that  of  standard  solu- 
tions of  blood  and  water  of  a  known  strength,  until  it  is  discovered 
to  what  standard  solution  the  diluted  blood  corresponds.  As  the 
amount  of  blood  in  the  corresponding  standard  solution  is  known,  as 
well  as  the  total  quantity  of  diluted  blood  obtained  from  the  animal, 
it  is  easy  to  calculate  the  absolute  amount  of  blood  which  the  latter 
contained,  and  to  this  is  added  the  small  amount  which  was  with- 
drawn to  make  the  standard  solutions.  This  gives  the  total  amount 
of  blood  which  the  animal  contained.  It  is  contrasted  with  the 
weight  of  the  animal,  previously  known.  The  result  of  experiments 
performed  in  this  way  showed  that  the  quantity  of  blood  in  various 
animals  differs  a  good  deal,  but  in  the  dog  averages  TV  to  ^  of 
the  total  body-weight.  In  smaller  animals  the  proportionate  blood 
volume  is  greater. 

Haldane  and  Lorrain  Smith  have  invented  another  method  which 
has  the  advantage  of  being  applicable  to  man.  The  data  required 
are  (1)  the  percentage  of  haemoglobin  in  the  blood,  and  (2)  the  extent 
to  which  the  haemoglobin  is  saturated  by  a  measured  amount  of 
carbonic  oxide  absorbed  into  the  blood. 

The  percentage  of  haemoglobin  is  determined  colorimetrically  by 
the  Gowers  or  Gowers-Haldane  haemoglobinometer  (see  p.  470).  In 
the  latter  instrument  the  standard  100  per  cent,  of  colour  corresponds 
to  a  capacity  of  18'5  c.c.  of  oxygen  or  carbonic  oxide  per  100  c.c.  of 
blood.  The  subject  whose  blood  is  to  be  measured  breathes  a  known 
volume  of  carbonic  oxide,  and  a  few  drops  of  the  blood  are  taken  and 
the  saturation  of  his  haemoglobin  is  determined  colorimetrically. 
From  this  result  the  total  capacity  of  the  blood  for  carbonic  oxide  is 
calculated.  The  "carbonic  oxide  capacity"  is  the  same  as  the 
"  oxygen  capacity."  The  volume  of  the  blood  is  then  calculated  from 
the  total  "  oxygen  capacity,"  and  the  percentage  capacity  as  deter- 
mined by  the  haemoglobinometer.  The  following  is  an  example : — The 
subject's  blood  in  a  given  case  has,  let  us  say,  the  colour  of  the  100 
per  cent,  standard,  and  therefore  has  a  capacity  of  18'5  c.c.  per 
100  c.c.  blood.  He  is  allowed  to  breathe  75  c.c.  of  carbonic  oxide, 
and  it  is  then  found  that  his  blood  is  15  per  cent,  saturated  with 
that  gas.  That  is  to  say,  instead  of  there  being  18-5  c.c.  of  oxygen 


446  THE  BLOOD  [CH.  XXIX. 

per  100  c.c.  of  blood,  15  per  cent,  of  this  18-5  c.c.  is  present  in  the 
form  of  carbonic  oxide,  15  per  cent,  of  18-5=  —     =.  —  =  2-7  c.c. 


Now  if  2-7  c.c.  of  carbon  monoxide  per  100  c.c.  of  blood  is  the  result 
of  breathing  75  c.c.  of  that  gas,  the  question  before  us  is,  How  much 
gas  will  be  necessary  to  produce  the  normal  figure  18-5  ? 

2-7  c.c.  per  100  c.c.  of  blood  results  from  breathing  75  c.c.  of  CO 

75_ 

.  .        X  C.C.  ,,  „  „  f.  j_  ,, 

75x18-5 
and      18-5  c.c.         „  „  „  —  ^7  —  » 

-     500  c.c. 

(approximately). 

In  other  words,  the  total  oxygen  (or  CO)  capacity  of  the  person's 
blood  is  500  c.c.  Since  18-5  c.c.  of  this  total  is  carried  by  100  c.c. 
of  blood,  the  total  volume  of  the  person's  blood,  that  is,  the  amount 

which  will  contain  500  c.c.  of  gas,  is  —  ^-=  —  =  2727  c.c.,  or  nearly 

-Lo*  0 

three  litres.  The  total  weight  of  the  blood  is  obtained  by  multiply- 
ing the  volume  by  the  specific  gravity  (about  1-055). 

Some  of  the  results  of  this  method  are  as  follows  :  —  The  mass  of 

the  blood  in  man  is  about  4*9  per  cent.  (  ^-^  )   of  the  body-  weight. 

' 


The  corresponding  ratio  of  the  blood  volume  is  4'62  c.c.  per  100 
grammes,  or  -^—  ^  In  pathological  conditions  the  numbers  are 

different;  thus  in  ansemia  from  hsemorrhage,  the  volume  ratio  is  6*5, 
in  pernicious  anaemia  8*6,  in  chlorosis  10'8.  In  other  words,  in 
various  forms  of  ansemia  the  actual  volume  of  the  blood  is  increased, 
but  of  course  the  corpuscular  and  solid  constituents  are  correspond- 
ingly diminished. 

Coagulation  of  the  Blood. 

After  the  blood  is  shed  it  rapidly  becomes  more  viscous  and  then 
sets  into  a  firm  red  jelly.  The  jelly  soon  contracts  and  squeezes  out 
a  straw-coloured  fluid  called  the  serum.  With  the  microscope, 
filaments  or  fine  threads  are  seen  forming  a  network  throughout  the 
fluid  (fig.  317),  many  radiating  from  small  clumps  of  blood-platelets. 
These  threads  entangle  the  corpuscles,  and  so  the  clot  is  formed. 
The  threads  are  composed  of  a  protein  substance  called  fibrin,  and 
the  formation  of  fibrin  is  the  essential  act  of  coagulation.  Fibrin  is 
formed  from  the  plasma,  and  may  be  obtained  free  from  corpuscles 
when  plasma  is  allowed  to  clot,  the  corpuscles  having  previously 
been  removed  by  methods  we  shall  immediately  study.  It  may  also 


CH.  XXIX.] 


COAGULATION    OF   THE    BLOOD 


447 


be  obtained  from  blood  by  whipping  it  with  a  bunch  of  twigs ;  the 
fibrin  adheres  to  the  twigs  and  entangles  but  few  corpuscles ;  these 
may  be  removed  by  subsequent  washing  with  water. 


FIG.  317. — Reticulum  of  fibrin,  from  a  drop  of  human  blood,  after  treatment  with  rosanilin.    The 
entangled  corpuscles  are  not  seen.    (Ranvier.) 

Serum  is  plasma  minus  the  fibrin  which  it  forms.  The  relation 
of  plasma,  serum,  and  clot  can  be  seen  at  a  glance  in  the  following 
scheme  of  the  constituents  of  the  blood : — 


Blood 


Plasma 


/Serum 
IFibriir 


Clot 


.Corpuscles 


It  may  be  roughly  stated  that  in  100  parts  by  weight  of  blood  60-65 
parts  consist  of  plasma  and  35-40  of  corpuscles. 

The  huffy  coat  is  seen  when  blood  coagulates  slowly,  as  in  horse's 
blood.  The  red  corpuscles  sink  more  rapidly  than  the  white,  and 
the  upper  stratum  of  the  clot  (buffy  coat)  consists  mainly  of  fibrin 
and  white  corpuscles. 

Coagulation  is  hastened  by — 

1.  A  temperature  a  little  over  that  of  the  body. 

2.  Contact  with  foreign  matter. 

3.  Injury  to  the  vessel  walls. 

4.  Agitation. 

5.  Addition  of  calcium  salts. 

6.  Injection  of  nucleo -protein  into  the  circulation  causes  intra- 

vascular  clotting. 

Coagulation  is  hindered  or  prevented  by — 
1.  A  low  temperature.     In  a  vessel  cooled  by  ice,  coagulation 

may  be  prevented  for  an  hour  or  more. 


448  THE   BLOOD  [CH.  XXIX. 

2.  The  addition  of  a  large  quantity  of  neutral  salts  such  as  sodium 

sulphate  or  magnesium  sulphate. 

3.  Addition  of  a  soluble  oxalate,  fluoride,  or  citrate. 

4.  Injection  of  commercial  peptone   (which  consists  chiefly  of 

proteoses)  into  the  circulation  of  the  living  animal. 

5.  Addition  of  leech  extract  to  the  blood,  or  injection  of  leech 

extract  into  the  circulation  while  the  animal  is  alive. 

6.  Contact  with  the  living  vascular  walls. 

7.  Contact  with  oil. 

The  cause  of  the  coagulation  of  the  blood  may  be  briefly  stated 
as  follows : — 

When  blood  is  within  the  vessels,  one  of  the  constituents  of  the 
plasma,  a  protein  of  the  globulin  class,  called  fibrinogen,  exists  in  a 
soluble  form.  When  the  blood  is  shed,  the  fibrinogen  molecule  is 
altered  in  such  a  way  that  it  gives  rise  to  the  comparatively  insoluble 
material  fibrin. 

The  statement  has  been  made  that  the  fibrinogen  molecule  is  split  into  two 
parts  ;  one  part  is  a  globulin  (fibrino-globulin),  which  remains  in  solution ;  the 
other  and  larger  part  is  the  insoluble  substance  fibrin.  It  is,  however,  doubtful  if 
this  really  represents  what  occurs,  for  recent  work  seems  to  show  that  the  fibrino- 
globulin  is  not  a  product  of  fibrinogen,  but  exists  in  the  blood-plasma  beforehand. 
At  any  rate,  whether  this  is  so  or  not,  the  fact  remains  that  fibrin  is  the  important 
product  and  the  only  one  which  need  concern  us. 

The  next  question  is,  What  causes  the  transformation  of  fibrinogen 
into  fibrin  ?  and  the  answer  to  that  is,  that  the  change  is  due  to  the 
activity  of  an  enzyme  which  is  called  fibrin-ferment  or  thrombin. 

This  enzyme  does  not  exist  in  healthy  blood  contained  in  healthy 
blood-vessels,  but  is  formed  by  the  disintegration  of  the  blood- 
platelets  and  colourless  corpuscles  which  occurs  when  the  blood 
leaves  the  blood-vessels  or  comes  into  contact  with  foreign  matter. 
Hence  the  blood  does  not  coagulate  during  life.  But  it  will  be  said, 
disintegration  of  the  blood- corpuscles  occurs  during  life,  why,  then, 
does  the  blood  not  coagulate?  The  reason  is,  that  although  the 
formed  elements  do  disintegrate  in  the  living  blood,  such  a 
phenomenon  takes  place  very  slowly  and  gradually,  so  that  there 
can  never,  under  normal  circumstances,  be  any  massive  liberation 
of  fibrin-ferment,  and  further,  that  there  are  agencies  at  work  to 
neutralise  the  fibrin-ferment  as  it  is  formed.  The  most  noteworthy 
of  these  neutralising  agencies  is  the  presence  in  the  blood  of  an 
antiferment  called  antithrombin,  analogous  to  the  antipepsin  and 
antitrypsin  which  we  shall  see  are  efficacious  in  preventing  the 
stomach  and  intestines  from  undergoing  self-digestion. 

Nucleo-proteins  obtained  from  most  of  the  cellular  organs  of 
the  body  produce  intravascular  clotting  when  injected  into  the 
circulation  of  a  living  animal.  In  certain  diseased  conditions  intra- 
vascular clotting  or  thrombosis  sometimes  occurs,  and  this,  if  it 


CH.  XXIX.]  COAGULATION   OF  THE   BLOOD  449 

occurs  in  the  heart  and  main  blood-vessels,  is  fatal.  The  condition 
is  doubtless  due  to  the  entrance  of  nucleo-protein  into  the  circula- 
tion from  disintegrated  cells.  The  relationship  of  nucleo-protein 
and  thrombin  is  an  unsettled  problem ;  the  old  view  that  the  two 
are  identical  is  probably  incorrect ;  it  is,  however,  possible  that  the 
nucleo-protein  is  either  identical  with  thrombokinase,  or  holds  the 
thrombokinase  in  loose  combination  or  admixture. 

Thrombin  is  believed  to  originate  chiefly  from  the  blood-platelets 
and  in  part  from  the  leucocytes.  Birds'  blood  clots  very  slowly, 
and  the  absence  of  blood-platelets  in  this  variety  of  blood  will,  in 
part,  account  for  this.  Lymph,  which  contains  colourless  cor- 
puscles, but  no  platelets,  also  clots,  so  in  this  case  the  colourless 
corpuscles  must  be  the  source  of  the  ferment.  One  should,  however, 
be  careful  in  speaking  of  the  disintegration  of  leucocytes  to 
remember  that  the  word  disintegration  does  not  mean  complete 
breakdown  leading  to  disappearance;  the  colourless  corpuscles  do 
not  appreciably  diminish  in  number  when  the  blood  clots,  but  what 
occurs  is  a  shedding  out  from  the  surviving  leucocytes  of  certain 
products,  among  which  fibrin-ferment  is  one. 

We  have  now  traced  fibrin  formation,  the  essential  cause  of 
blood-clotting,  to  the  activity  of  thrombin ;  it  is  next  necessary  to 
allude  to  what  has  been  discovered  in  relation  to  the  origin  of 
thrombin.  Like  other  enzymes,  it  is  preceded  by  a  mother-substance 
or  zymogen.  This  zymogen  is  called  pro  thrombin  or  thrombogen, 
and  there  appear  to  be  two  necessary  agents  concerned  in  the 
conversion  of  thrombogen  into  thrombin ;  one  of  these  is  the  action 
of  calcium  salts,  the  other  is  the  presence  of  an  activating  agent 
(analogous  to  the  enterokinase,  which  activates  pancreatic  juice) 
called  thrombokinase. 

The  part  played  by  calcium  salts  is  well  illustrated  by  the  fact 
that  coagulation  is  prevented  by  the  decalcification  of  the  blood. 
This  can  be  accomplished  by  the  addition  of  a  small  amount  of  a 
soluble  oxalate  or  fluoride  to  the  blood  immediately  it  is  shed.  The 
calcium  of  the  blood  plasma  is  then  immediately  precipitated  as 
insoluble  calcium  oxalate  or  fluoride,  and  is  thus  not  available  for 
the  transformation  of  thrombogen  into  thrombin.  The  addition  of  the 
oxalate  or  fluoride  must  be  rapidly  performed,  otherwise  time  will  be 
given  for  the  conversion  of  thrombogen  into  thrombin,  and  thrombin, 
when  formed,  will  act  upon  fibrinogen  whether  the  calcium  has  been 
removed  or  not.  In  other  words,  calcium  is  only  necessary  for  the 
formation  of  fibrin-ferment,  and  not  for  the  action  of  fibrin-ferment 
on  fibrinogen.  Fibrin  is  thus  not  a  compound  of  calcium  and 
fibrinogen. 

The  action  of  a  soluble  citrate  is  also,  in  a  certain  sense,  a 
decalcifying  action,  for  although  calcium  citrate  is  a  soluble  salt,  it 

2  F 


450  THE    BLOOD  [CH.  XXIX. 

does  not  ionise  in  solution  so  as  to  liberate  the  free  calcium  ions 
which  are  essential  for  thrombin  formation. 

Oxalated  blood  (or  oxalated  plasma)  will  clot  when  the  calcium 
is  once  more  restored  by  the  addition  of  a  small  amount  of  calcium 
chloride,  but  such  addition  to  fluoride  plasma  will  not  induce  clotting ; 
in  this  case,  thrombin  itself  must  be  added  as  well.  In  some  way 
sodium  fluoride  interferes  with  the  formation  of  thrombin,  probably 
by  preventing  the  liberation  of  thrombokinase  from  the  corpuscular 
elements  of  the  blood.  The  latter  are  certainly  very  well  preserved. 

The  second  activating  agent,  however,  thrombokinase,  is  not  only 
liberated  from  the  blood-corpuscles,  but  it  is  also  obtained  from  many 
other  tissues.  If  a  haemorrhage  takes  place  under  ordinary  circum- 
stances the  blood  as  it  flows  from  the  wound  passes  over  the  muscles 
and  skin  that  have  been  cut,  and  rapidly  clots  owing  to  the  throm- 
bokinase supplied  by  those  tissues.  If  blood  is  obtained  by  drawing 
it  off  through  a  perfectly  clean  cannula  into  a  clean  vessel  without 
allowing  it  to  touch  the  tissues,  it  remains  unclotted  for  a  long 
time ;  in  the  case  of  birds'  blood  this  time  may  extend  to  many  days ; 
but  the  addition  of  a  small  piece  of  a  tissue  such  as  muscle,  or  of  an 
extract  of  such  a  tissue,  produces  almost  immediate  clotting.  If  a 
solution  of  fibrinogen  is  prepared  and  calcium  added  it  will  not  clot ; 
if  thrombin,  or  a  fluid  such  as  serum  which  contains  thrombin,  is  added 
it  will  clot.  It  will  not  clot  if  birds'  plasma  obtained  as  above  is  added 
to  it ;  nor  if  tissue  extract  is  added  to  it ;  but  if  both  are  added  it  will. 
In  other  words,  the  thrombogen  of  the  birds'  plasma  plus  the  throm- 
bokinase of  the  tissue  extract  have  the  same  effect  as  thrombin. 

The  next  point  to  consider  is  why  blood  obtained  after  the 
previous  injection  of  proteoses  (or  commercial  peptone)  into  the 
circulation  does  not  clot.  It  certainly  contains  calcium  salts,  and 
probably  both  thrombogen  and  thrombokinase,  for  it  can  be  made  to 
clot  without  the  addition  of  either,  for  instance  by  dilution,  or  the 
passage  of  a  stream  of  carbon  dioxide  through  it.  There  must  be 
something  in  peptone  blood  which  antagonises  the  action  of  thrombin. 
This  something  is  an  excess  of  . an ti thrombin.  Peptone  will  not 
hinder  blood:coagulation,  or  only  very  slightly,  if  it  is  added  to  the 
blood  after  it  is  shed.  The  antithrombin  must  therefore  have  been 
added  to  the  blood  while  it  was  circulating  in  the  body.  We  can 
oven  go  further  than  this,  and  say  what  part  of  the  body  it  is  which 
is  concerned  in  the  production  of  antithrombin.  It  is  the  liver ;  for 
if  the  liver  is  shut  off  from  the  circulation,  peptone  is  ineffective  in 
its  action.  The  converse  experiment  confirms  this  conclusion,  for  if 
a  solution  of  peptone  is  artificially  perfused  through  an  excised 
surviving  liver,  a  substance  is  formed  which  has  the  power  of  hinder- 
ing or  preventing  the  coagulation  of  shed  blood.  Peptone  blood  is 
very  poor  in  leucocytes;  the  cause  of  their  disappearance  is  not  clear. 


en.  xxix.] 


COAGULATION   OF   THE   BLOOD 


451 


We  are  thus  justified  in  two  conclusions: — 

(1)  That  the  antithrombin  (normally  present  in  healthy  blood  in 
sufficient  quantities  to  prevent  intravascular  clotting)  is  formed  in 
the  liver. 

(2)  That    commercial    peptone,   in    virtue    of    the    proteoses   it 
contains,  stimulates   this   action   to   such   an   extraordinary  degree 
that   the   accumulation   of  antithrombin   in    the  blood  becomes  so 
great  that  the  blood  does  not  clot  even  after  it  is  shed. 

We  will  conclude  by  considering  only  one  more  of  the  hindrances 
to  coagulation,  and  that  by  no  means  the  least  interesting.  The 
leech  lives  by  sucking  the  blood  of  other  animals ;  from  the  leech's 
point  of  view  it  is  therefore  necessary  that  the  blood  should  flow 
freely  and  not  clot.  The  glands  at  the  head  end  of  the  leech,  often 
spoken  of  roughly  as  its  salivary  glands,  secrete  something  which 
hinders  the  blood  from  coagulating,  and  everyone  knows  by  experi- 
ence, who  has  been  treated  by  leeches,  how  difficult  it  is  to  prevent 
a  leech-bite  from  bleeding  after  the  leech  has  been  removed ;  com- 
plete cleansing  is  necessary  to  wash  away  the  leech's  secretion  from 
the  wound.  Now  if  an  extract  of  leeches'  heads  is  made  with  salt 
solution  and  filtered,  that  fluid  will  prevent  coagulation  whether  it  is 
injected  into  the  blood-stream  or  added  to  shed  blood.  The  sub- 
stance in  question  is  believed  to  be  antithrombin  itself.  The 
purified  material  obtained  from  leech  extract  is  called  hirudin. 
Blood  so  obtained  can  be  made  to  clot  by  the  addition  of  thrombin,  or 
of  such  a  fluid  as  serum,  that  contains  thrombin  in  sufficient  amount. 

We  may  summarise  this  view  of  the  causes  of  coagulation  in 
the  following  tabular  way  : — 


From  the  platelets,  and 
to  a  lesser  degree  from  the 
leucocytes,  a  material  is 
shed  out,  called — 


TH  ROM  BOG  EN. 

I 


From  the  formed  ele- 
ments of  the  blood,  but 
also  from  the  tissues  over 
which  the  escaping  blood 
flows,  is  shed  out  an  acti- 
vating agent,  called — 

THROMBOKINASE. 

I 


In  the  blood  plas-  In  the   presence   of  CALCIUM   salts,   thrombokinase 

ma    a    protein    sub-       activates   thrombogen  in  such  a  way  that  an  active 
stance  exists, called—       enzyme  is  produced,  which  is  called— 


FlBRlNOGEN. 

I 


THROMBIN. 

•       I 


Thrombin  or  fibrin-ferment  acts  on  fibrinogen  in  such  a  way  that  it  is  trans- 
formed into  the  insoluble  stringy  material  which  is  called — 

FIBRIN. 

Differing  hypotheses  are  held  as  to  the  exact  role  played  by  each  of  the  factors 
in  fibrin-formation,  and  the  views  enunciated  in  the  preceding  paragraphs  are  in  the 


452  THE   BLOOD  [CH.  XXIX. 

main  those  of  Morawitz.  Ho  well  regards  the  lack  of  coagulation  seen  in  birds' 
blood,  and  peptone  blood,  as  due  to  excess  of  antithrombin,  but  holds  that  throra- 
bokinase  (or  thromboplastin,  as  he  terms  it)  brings  about  clotting,  not  by  activating 
thrombogen,  but  by  neutralising  antithrombin.  According  to  him,  also,  thrombo- 
plastin is  probably  a  lipoid  of  the  phosphatide  group. 

The  Plasma  and  Serum. 

The  liquid  in  which  the  corpuscles  float  may  be  obtained  by 
employing  one  or  other  of  the  methods  already  described  for  pre- 
venting the  blood  from  coagulating.  The  corpuscles,  being  heavy, 
sink,  and  the  supernatant  plasma  can  then  be  removed  by  a  pipette 
or  siphon ;  the  separation  can  be  more  rapidly  effected  by  the  use  of 
a  centrifugal  machine. 

On  counteracting  the  influence  which  has  prevented  the  blood 
from  coagulating,  the  plasma  then  itself  coagulates.  Thus  plasma 
obtained  by  the  use  of  cold  clots  on  warming  gently }  plasma  which 
has  been  decalcified  by  the  action  of  a  soluble  oxalate  clots  on  the 
addition  of  a  calcium  salt ;  plasma  obtained  by  the  use  of  a  strong 
solution  of  neutral  salt  coagulates  when  this  is  diluted  by  the  addition 
of  water,  the  addition  of  fibrin-ferment  being  necessary  in  most  cases ; 
where  coagulation  occurs  without  the  addition  of  fibrin-ferment  no 
doubt  some  is  present  from  the  partial  disintegration  of  the  corpuscles 
which  has  already  occurred.  Pericardial  and  hydrocele  fluids 
resemble  pure  plasma  very  closely  in  composition.  As  a  rule, 
however,  they  contain  few  or  no  white  corpuscles,  and  do  not  clot 
spontaneously,  but  after  the  addition  of  fibrin-ferment,  or  of  liquids 
such  as  serum  that  contain  fibrin-ferment,  they  always  yield  fibrin. 

Pure  plasma  may  be  obtained  from  horse's  veins  by  what  is  known 
as  the  "  living  test-tube  "  experiment.  If  the  jugular  vein  is  ligatured 
in  two  places  so  as  to  include  a  quantity  of  blood  within  it,  then 
removed  from  the  animal  and  hung  in  a  cool  place,  the  blood  will  not 
clot  for  many  hours.  The  corpuscles  settle,  and  the  supernatant 
plasma  can  be  removed  with  a  pipette. 

The  plasma  is  alkaline,  yellowish  in  tint,  and  its  specific  gravity 
is  about  1026  to  1029.  1000  parts  of  plasma  contain : — 

Water 902-90 

Solids 97-10 

Proteins  :  1.  yield  of  fibrin 4-05 

2.  other  proteins 78 -84 

Extractives  (including  fat) 5 '66 

Inorganic  salts 8 '55 

In  round  numbers,  plasma  contains  10  per  cent,  of  solids,  of  which 
8  are  protein  in  nature.  Fibrinogen,  as  judged  from  the  yield  of 
fibrin,  is  the  least  abundant  of  the  proteins  present. 

Serum  contains  the  same  three  classes  of  constituents — proteins, 
extractives,  and  salts.  The  extractives  and  salts  are  the  same  in 


CH.  XXIX.]  PLASMA   AND   SERUM  453 

both  liquids.     The  proteins  are  different,  as  is  shown  in  the  following 
table : — 

Proteins  of  Plasma.  Proteins  of  Serum. 

Fibrin  ogen.  Serum  globulin. 

Serum  globulin.  Serum  albumin. 

Serum  albumin.  Fibrin-ferment  +  nucleo-protein. 

The  gases  of  plasma  and  serum  are  small  quantities  of  oxygen, 
nitrogen,  and  carbonic  acid.  The  greater  part  of  the  oxygen  of  the 
blood  is  combined  in  the  red  corpuscles  with  haemoglobin;  the 
carbonic  acid  is  chiefly  combined  as  carbonates.  The  gases  of  the 
blood  have  already  been  considered  under  Eespiration  (see  pp.  361- 
372). 

We  may  now  study  one  by  one  the  various  constituents  of  the 
plasma  and  serum. 

A.  Proteins. — Fibrinogen,  the  mother-substance  of   fibrin,   is  a 
globulin.     It  differs  from  serum  globulin,  and  may  be  separated  from 
it  by   making   use  of    the   fact   that   half-saturation   with   sodium 
chloride  precipitates  it.     It  coagulates  by  heat  at  the  low  tempera- 
ture of  56°  C. 

Serum  globulin  and  serum  albumin. — These  substances  exhibit  the 
usual  differences  already  described  between  albumins  and  globulins 
(p.  428).  Both  are  coagulated  by  heat  at  a  little  over  70°  C.  They 
may  be  separated  by  dialysis  or  the  use  of  neutral  salts.*  The 
readiest  way  to  separate  them  is  to  add  to  the  serum  an  equal  volume 
of  saturated  solution  of  ammonium  sulphate.  This  is  equivalent  to 
semi-saturation,  and  it  precipitates  the  globulin.  If  magnesium 
sulphate  is  used  as  a  precipitant  of  the  globulin  it  must  be  added  in 
the  form  of  crystals,  and  the  mixture  well  shaken  to  ensure  complete 
saturation. 

Fibrin-ferment  or  Thrombin. — Schmidt's  method  of  preparing  it 
is  to  take  serum  and  add  excess  of  alcohol.  This  precipitates  all  the 
proteins  and  the  thrombin.  After  some  weeks  the  alcohol  is  poured 
off;  the  serum  globulin  and  serum  albumin  have  been  by  this  means 
rendered  insoluble  in  water;  an  aqueous  extract  is,  however,  found 
to  contain  fibrin-ferment,  which  is  not  so  easily  coagulated  by  alcohol 
as  the  proteins  are. 

B.  Extractives. — These   are   non-nitrogenous   and    nitrogenous. 
The   non-nitrogenous   are   fats,   soaps,   cholesterin,   and  sugar;   the 
nitrogenous   are   urea   (0*02   to   0'04   per   cent.),   and   still   smaller 
quantities   of   uric   acid,   creatine,   creatinine,  xanthine,  and   hypo- 
xanthine  and  ammo-acids. 

*  The  globulin  of  the  serum  precipitated  by  "  salting  out"  really  consists  of 
two  proteins,  one  of  which  is  precipitated  by  dialysis  (euglobulin),  and  the  other  is 
not  (pseudo-globulin). 


454  THE   BLOOD  [cii.  XXIX. 

C.  Salts. — The  most  abundant  salt  is  sodium  chloride;  it  con- 
stitutes between  60  and  90  per  cent,  of  the  total  mineral  matter. 
Potassium  chloride  is  present  in  much  smaller  amount.  It  consti- 
tutes about  4  per  cent,  of  the  total  ash.  The  other  salts  are 
phosphates  and  sulphates. 

Schmidt  gives  the  following  table : — 

1000  parts  of  plasma  yield — 

Mineral  matter  .........  8*550 

Chlorine 3-640 

SO3 0-115 

P2O5 0-191 

Potassium 0-323 

Sodium 3-341 

Calcium  phosphate 0*311 

Magnesium  phosphate 0-222 

The  Blood- Corpuscles. 

Red  or  Coloured  Corpuscles. — Human  red  blood -corpuscles  are 
circular  biconcave  discs  with  rounded  edges,  -g^Vo  inch  in  diameter 
(7  JUL  to  8  JUL)  and  T2ihro-  inch,  or  about  2  /z,  in  thickness.  When  viewed 
singly  they  appear  of  a  pale  yellowish  tinge ;  the  deep  red  colour 
which  they  give  to  the  blood  is  observable  in  them  only  when  they 
are  seen  en  masse. 

According  to  Rollett  they  are  composed  of  a  transparent  filmy  framework 
infiltrated  in  all  parts  by  the  red  pigment  haemoglobin.  This  stroma  is  elastic,  so 
that  as  the  corpuscles  circulate,  they  admit  of  change  in  form,  and  recover  their 
natural  shape  as  soon  as  they  escape  from  compression.  According  to  this  theory, 
the  consistency  of  the  peripheral  part  of  the  stroma  is  greater  than  that  of  the 
central  portions  ;  the  outer  layer  thus  plays  the  part  of  a  membrane  in  the  processes 
of  osmosis  that  occur  when  water  or  salt  solutions  are  added  to  the  corpuscles. 
This  view  of  Rollett  has  been  questioned,  particularly  by  Schafer,  who  regards  the 
red  corpuscles  as  composed  of  a  colourless  envelope  enclosing  a  solution  of  haemo- 
globin. The  presence  of  a  membrane  on  the  exterior  of  the  corpuscle  is  undoubted, 
and  can  be  clearly  distinguished  by  a  good  microscope  in  the  larger  corpuscles  of 
amphibia.  It  is,  however,  difficult  to  explain  the  elasticity  of  the  corpuscles,  and 
the  central  position  of  the  nucleus  in  nucleated  red  corpuscles,  unless  we  also  assume 
that  delicate  fibres  pass  across  the  interior  of  the  corpuscles. 

The  red  corpuscles  of  other  mammals  are  generally  very  nearly 
the  size  of  human  red  corpuscles.  They  are  smallest  in  the  deer 
tribe  and  largest  in  the  elephant.  In  the  camelidae  they  are 
biconvex.  In  all  mammals  the  corpuscles  are  non-nucleated,  and 
in  all  other  vertebrates  (birds,  reptiles,  amphibia,  and  fishes)  the 
corpuscles  are  oval,  biconvex,  and  nucleated  (fig.  319),  and  larger 
than  in  mammals.  They  are  largest  of  all  in  certain  amphibians 
(amphiuma,  proteus). 

A  property  of  the  red  corpuscles,  which  is  exaggerated  in  inflam- 
matory blood,  is  a  tendency  to  adhere  together  in  rolls  or  columns 
(rouleaux),  like  piles  of  coins.  These  rolls  quickly  fasten  together 


CIL  XXIX.] 


THE    BLOOD-CORPUSCLES 


455 


by  their  ends,  and  cluster;  so  that,  when  the  blood  is  spread  out  thinly 
on  a  glass  they  form  an  irregular  network  (fig.  318). 


.      .  FIG.  319.— Corpuscles  of  the  frog.     The 

*  10.  318.-Red  corpuscles  in  rouleaux.    The  central  mass  consists    of  nucleated 

white  corpuscles  are  uncoloured.  coloured  corpuscles.    The  other  cor- 

puscles   are    two    varieties    of    the 
colourless  form. 

Action  of  Reagents. — Considerable  light  has  been  thrown  on  the  physical  and 
chemical  constitution  of  red  blood-cells  by  studying  the  effects  produced  by 
mechanical  means  and  by  various  reagents  ;  the  following  is  a  brief  summary  of 
these  reactions  : — 

Water. — When  water  is  added  gradually  to  frog's  blood,  the  oval  disc-shaped 
corpuscles  become  spherical,  and  gradually  discharge  their  haemoglobin,  a  pale, 
transparent  envelope  being  left  behind :  human  red  blood-cells  swell,  change 
from  a  discoidal  to  a  spheroidal  form,  burst  and  discharge  their  pigment,  becoming 
quite  transparent  and  all  but  invisible.  This  effect  is  due  to  osmosis. 

Physiological  saline  solution  causes  no  effect  on  the  red  corpuscles  beyond  pre- 
venting them  running  into  rouleaux.     If  a  stronger  salt  solution  is  used,  the  cor- 
puscles shrink  and  become  crenated  (fig.  320),  owing  to  osmosis  of  water  outwards. 
Dilute  acetic  acid  causes  the  nucleus  of  the  red  blood-cells  in 
$k  <tfk  the   frog  to   become    more  clearly  defined ;   if  the  action  is  pro- 

longed, the  nucleus  becomes  strongly  granulated,  and  all  the 
colouring  matter  seems  to  be  concentrated  in  it,  the  surrounding 
cell-substance  and  outline  of  the  cell  becoming  almost  invisible ; 
after  a  time  the  cells  lose  their  colour  altogether.  A  similar 
loss  of  colour  occurs  in  the  red  corpuscles  of  human  blood, 
which,  however,  from  the  absence  of  nuclei,  seem  to  disappear 
entirely. 

Dilute  alkalis  cause  the  red  blood-cells  to  dissolve  slowly,  and  finally  to  disappear. 
Chloroform,  ether,  and  other  reagents  that  dissolve  fats  dissolve  the  lipoid 
subsfances  (lecithin,  etc.)  of  the  membrane  which  surrounds  the 
corpuscles,  and  so  produce  taking  of  the  blood. 

Tannic  acid. — When  a  2  per  cent,  fresh  solution  of  tannic 
acid  is  applied  to  frog's  blood  it  causes  the  appearance  of  a 
sharply-defined  little  knob,  projecting  from  the  free  surface 
(Roberts'  macula) :  the  colouring  matter  becomes  at  the  same 
time  concentrated  in  the  nucleus,  which  grows  more  distinct 
(fig.  321).  A  somewhat  similar  effect  is  produced  on  the  human 
red  blood-corpuscle,  the  colouring  matter  being  discharged 
and  coagulated  as  a  little  knob  of  haematin  on  the  surface  of  the  corpuscle. 


FIG.  320.-Effect 
of  saline  solu- 
tion (crena- 
tion). 


FIG.  321.— Effect  of 
tannin. 


456  THE   BLOOD  [CH.  XXIX. 

The  Colourless  Corpuscles. — The  white  or  colourless  corpuscles 
"are  masses  of  nucleated  protoplasm ;  they  are  nearly  spherical  when 
at  rest,  but  owing  to  their  amoeboid  movements  (see  p.  11)  exhibit 
considerable  changes  in  outline  when  they  are  active,  as  they  are  at 
body  temperature. 

In  health,  the  proportion  of  white  to  red  corpuscles  is  on  the 
average  1  to  500  or  600,  but  this  varies  considerably  even  in  the 
course  of  the  same  day.  The  number  of  lymphocytes  is  greatly 
increased  by  a  meal.  Also,  in  young  persons,  after  haemorrhage  and 
during  pregnancy,  there  is  a  larger  proportion  of  colourless  blood - 
corpuscles ;  in  old  age  they  are  diminished. 

Several  varieties  of  colourless  corpuscles  are  found  in  human 
blood.  They  are  represented  in  the  accompanying  coloured  plate, 
stained  by  different  methods ;  the  column  on  the  left  shows  their 
appearances  as  stained  by  a  mixture  of  eosin  and  methylene  blue 
(Jenner's  stain).  The  middle  column  shows  them  as  stained  by 
Ehrlich's  triacid  dye  (acid  fuchsin,  methyl-green,  and  orange  G-). 
In  the  right-hand  column,  the  cells  were  stained  with  a  mixture  of 
haematoxylin  and  eosin.  The  following  are  the  varieties  shown : — 

(a)  Lymphocytes. — These    are    only    a    little    larger    than    red 
corpuscles.     The  nucleus  is  relatively  large,  and  usually  round ;  the 
protoplasm  around  it  forms  quite  a  narrow  zone.     The  nucleus,  as  is 
the  case  with  all  nuclei,  is  basophile,  and  stains  with  such  basic  dyes 
as  methylene  blue.     The  protoplasm  presents  no  distinct  granules 
and  is  also  basophile.     The  lymphocytes  comprise  about  25  per  cent, 
of  the  total  colourless  corpuscles. 

(b)  Large  mononuclear  leucocytes. — A  relatively  small  oval  nucleus 
lies  near  the  centre  of  basophile  protoplasm,  which  again  presents  no 
definite  granulation.     Their  diameter  is  12-20  /*,  and  they  form  only 

1  per  cent,  of  the  total  colourless  corpuscles. 

(c)  Transitional  leucocytes. — The  cell-body  is  somewhat  smaller 
and  is  mainly  basophile.     A  certain  amount  of  neutrophile  granula- 
tion may  be  seen.     The  strongly  basophile  nucleus  may  present  all 
gradations  between  an  oval  and  lobed  condition.     In  normal  blood 
their  number  is  variable,  but,  as  a  rule,  they  only  make  up  about 

2  to  4  per  cent,  of  the  total  colourless  corpuscles.     They  are  called 
transitional  on  the  hypothesis  that  they  represent  an  intermediate 
condition  between  the  large  mononuclear  leucocytes  and  the  poly- 
nuclear  leucocytes  described  under  d.     It  is,  however,  doubtful  if 
this  hypothesis  is  correct,  and  some  histologists  think  the  b  and  c 
varieties  originate  from  the  endothelial  wall. 

(d)  Polynuclear  leucocytes.— These  are   9-12  /UL  in  diameter,  and 
form  the  main  mass  of   the  colourless  corpuscles  (70   per   cent.). 
They  have  several  nuclei,  which  are  strongly  basophile  and  present 
many  different   shapes,  and   are   usually  connected   by  threads  of 


a 


a 


r 


Stained  with 

Methylene  Blue 

and  Eosin. 


Stained  with 

Ehrlich's 
Tri-acid  Dye. 


Stained  with 

Hsematoxylin 

and  Eosin. 


The  varieties  of  colourless  corpuscles  in  normal  human  blood, 
stained  by  different  methods. 

a,  Lymphocyte;  b,  large  mono-nuclear  hyaline  leucocyte;  c,  transition 
form ;  d,  polynuclear  leucocyte  ;  e,  eosinophile  leucocyte  ;  /,  mast-cell. 
Magnified  about  itiOO  times.  (After  Szymonowicz.) 


[Face  page  456. 


CH.  XXIX.] 


THE   COLOUELESS   CORPUSCLES 


457 


chromatin.  The  protoplasm  is  finely  granular,  and  stains  with 
neutral,  and  faintly  with  acid  aniline  dyes  (such  as  eosin).  In 
certain  pathological  conditions — for  instance,  in  diabetes — the  cell- 
protoplasm  contains  excess  of  glycogen. 

(e)  Eosinopliile  leucocytes. — These  are  usually  larger  than  the 
preceding  (12-15  JUL  in  diameter).  They  contain  either  a  single 
irregular-shaped  nucleus,  or  more  often  two  or  three  nuclei  of 
unequal  size.  Their  protoplasm  contains  large  distinct  granules 
which  have  an  intense  affinity  for  acid  dyes  such  as  eosin,  and  are 
therefore  termed  oxyphile,  acidophile,  or  eosinophile.  They  are 
stated  to  be  less  actively  amoeboid  than  the  polynuclear  leucocytes. 


Healthy  bacillus 

Healthy  bacillus k 


Healthy  bacillus. 

Partially  digested  bacillus. 


Partially  digested  leucocyte 

Nuclei  vacuolated  — 


Nucleus. 


-—Bacillus  in  leucocyte. 
A. .Partially  digested  leucocyte. 


--_--,•:__. Foreign  matter. 


Foreign  matter  _ fc; 


Particles  of  foreign  matter. 

Particles  of  foreign  matter. 
Leucocytes  '  ' i^ifl**- Particles  of  foreign  matter. 

FIG.  322.— Macrophages  containing  bacilli  and  other  structures  undergoing  digestion.    (Ruffer.) 

They  comprise  from  2  to  4  per  cent,  of  the  total  colourless 
corpuscles. 

(/)  Mast-cells. — These  cells  we  have  already  seen  in  the  connective 
tissues  (pp.  30-31)  and  they  are  very  rare  in  normal  blood.  Less  than 
0-5  per  cent,  is  usually  present.  They  measure  about  10  /x  across  ; 
their  nucleus  is  single  and  irregular  in  shape.  The  granules  in  the 
protoplasm  are  much  more  basophile  than  the  nucleus.  (See  coloured 
plate.) 

Phagocytosis. — The  most  important  outcome  of  the  amoeboid 
movement  of  the  colourless  corpuscles  is  their  power  of  ingesting 
foreign  particles,  such  as  bacteria,  which  they  engulf  and  digest. 


458 


THE   BLOOD 


[Cli.  XXIX. 


This  is  called  phagocytosis  (see  also  p.  298).  The  polynuclear  leuco- 
cytes appear  to  be  the  most  vigorous  phagocytes.  The  drawings  in 
fig.  322  show  some  stages  in  this  phenomenon;  the  cells  represented 
there,  however,  are  not  normal  leucocytes,  but  certain  large  amoeboid 
cells  found  in  connective  tissues,  which  congregate  specially  in 
inflamed  parts. 

The  Blood-Platelets. — Besides  the  two  principal  varieties  of 
blood-corpuscles,  a  third  kind  has  been  described  under  the  name 
blood-platelets  (Blut-pldtcJien).  These  are  colourless  disc-shaped  or 
irregular  bodies,  much  smaller  than  red  corpuscles.  Different  views 
are  held  as  to  their  origin.  At  first  they  were  regarded  as  immature 
red  corpuscles ;  but  this  view  has  been  discarded.  Some  state  that 
they  are  merely  a  precipitate  of  nucleo-protein  which  occurs  when 
the  plasma  dies  or  is  cooled.  There  is,  however,  no  doubt  that  they 
do  occur  in  living  blood,  and  have  been  seen  to  undergo  amoeboid 
movement ;  some  observers  state  that  they  are  nucleated. 

Enumeration  of  the  Blood-Corpuscles. 

Several  methods  are  employed  for  counting  the  blood-corpuscles  ;  most  of  them 
depend  upon  the  same  principle,  i.  e. ,  the  dilution  of  a  minute  volume  of  blood  with 
a  given  volume  of  a  colourless  saline  solution  similar  in  specific 
gravity  to  blood-plasma,  so  that  the  size  and  shape  of  the 
corpuscles  is  altered  as  little  as  possible.  A  minute  quantity 
of  the  well-mixed  solution  is  then  taken,  examined  under  the 
microscope  in  a  cell  of  known  capacity,  and  the  number  of 
corpuscles  in  a  given  area  of  the  cell,  is  counted.  Having 
ascertained  the  number  of  corpuscles  in  the  diluted  blood, 
it  is  easy  to  calculate  the  number  in  a  given  volume  of  normal 
blood. 

The  hsemacytometer  most  frequently  used  at  the  present 
time  is  known  as  the  Thoma-Zeiss  haemacytometer.  It 
consists  of  a  carefully  graduated  pipette,  in  which  the 
dilution  of  the  blood  is  done;  this  is  so  formed  that  the 
capillary  stem  has  a  capacity  equalling  one  -  hundredth  of 
the  bulb  above  it.  If  the  blood  is  drawn  up  in  the  capillary 
tube  to  the  line  marked  1  (fig.  323)  the  saline  solution  may 
afterwards  be  drawn  up  the  stem  to  the  line  101 ;  in  this  way  we 
have  101  parts,  of  which  the  blood  forms  1.  The  blood  and  the 
saline  solution  are  well  mixed  by  shaking  the  pipette,  in  the  bulb 
of  which  is  contained  a  small  glass  bead  for  the  purpose  of  aiding 
the  mixing.  The  other  part  of  the  instrument  consists  of  a 
glass  slide  (fig.  324)  upon  which  is  mounted  a  covered  disc,  m, 
accurately  ruled  so  as  to  present  one  square  millimetre  divided 
into  400  squares  of  one-twentieth  of  a  millimetre  each.  The 
micrometer  thus  made  is  surrounded  by  another  annular  cell,  c, 
which  has  such  a  height  as  to  make  the  cell  project  exactly 
one-tenth  millimetre  beyond  m.  If  a  drop  of  the  diluted 
blood  is  placed  upon  m,  and  c  is  covered  with  a  perfectly  flat 
cover-glass,  the  volume  of  the  diluted  blood  above  each  of  the 
squares  of  the  micrometer,  i.e.  above  each  4^,  will  be  ^VT.  of 
a  cubic  millimetre-  An  average  of  ten  or  more  squares  is  then 
taken,  and  this  number  multiplied  by  4000  x  100  gives  the 
number  of  corpuscles  in  a  cubic  millimetre  of  undiluted  blood.  The  average 
number  of  corpuscles  per  cubic  millimetre  of  healthy  blood,  according  to  Vierordt 


CH.  XXIX.]  OKIGIN   OF   RED   CORPUSCLES  459 

and  Welcker,  is  5,000,000  in  adult  men,  and  4,500,000  in  women ;  this  corre- 
sponds to  an  average  of  11-2  and  12  '5  corpuscles  respectively  per  square  of  the 
instrument. 


FIG.  324. 

The  enumeration  of  the  colourless  corpuscles  depends  on  the  same  principle, 
but  the  counting  has  to  be  carried  out  over  larger  areas  than  the  small  squares, 
and  the  differentiation  of  the  varieties  of  colourless  corpuscles  (which  is  most 
important  from  the  standpoint  of  disease)  can  be  accomplished  after  appropriate 
staining. 

Development  of  the  Blood-Corpuscles. 

Origin  of  the  Red  Corpuscles. — Surrounding  the  early  embryo 
is  a  circular  area,  called  the  vascular  area,  in  which  the  first  rudi- 


FIQ.  325.— Part  of  the  network  of  developing  blood-vessels  in  the  vascular  area  of  a  guinea-pig.  U, 
Blood-corpuscles  becoming  free  in  an  enlarged  and  hollowed-out  part  of  the  network ;  a,  process  of 
protoplasm.  (E.  A.  Schiifer.) 

ments  of  the  blood-vessels  and  blood-corpuscles  are  developed.  Here 
the  nucleated  embryonic  cells  of  the  mesoblast,  from  which  the  blood- 
vessels and  corpuscles  are  to  be  formed,  send  out  processes  in  various 
directions,  and  these,  joining  together,  form  an  irregular  mesh  work. 
The  nuclei  increase  in  number,  and  collect  chiefly  in  the  larger  masses 
of  protoplasm,  but  partly  also  in  the  processes.  These  nuclei  gather 
around  them  a  certain  amount  of  the  protoplasm,  and,  becoming 
coloured,  form  the  red  blood -corpuscles  (fig.  325).  The  protoplasm 
of  the  cells  and  the  branched  network  in  which  these  corpuscles  lie 
then  become  hollowed  out  into  a  system  of  canals  enclosing  fluid,  in 
which  the  red  nucleated  corpuscles  float.  The  corpuscles  at  first  are 
from  about  -arVir  to  T-^TT  of  an  inch  (10  /UL  to  16  /*)  in  diameter, 


460  THE   BLOOD  [CH.  XXIX. 

mostly  spherical,  and  with  granular  contents,  and  a  well-marked 
nucleus. 

The  corpuscles  then  strongly  resemble  the  colourless  corpuscles 
of  the  fully  developed  blood,  but  are  coloured.  They  are  capable  of 
amoeboid  movement  and  multiply  by  division. 

These  coloured  nucleated  cells  begin  very  early  in  foetal  life  to 
be  mingled  with  coloured  T^w-nucleated  corpuscles  resembling  those 
of  the  adult,  and  at  about  the  fourth  or  fifth  month  of  embryonic 
existence  are  completely  replaced  by  them. 

These  coloured  discs  are  partly  formed  in  connective-tissue 
cells  in  a  way  similar  to  that  just  described,  only  without  the 
participation  of  the  nuclei  in  the  process,  although  there  is  very 
little  doubt  that  haemoglobin  originates  from  the  haematogen  (iron- 
containing  nuclein)  of  the  nuclei  in  all  cases.  The  foetal  liver, 
spleen,  and  thymus  are  also  believed  to  be  seats  of  formation  of 
the  red  discs. 

Without  doubt,  the  red  corpuscles  have,  like  all  other  parts 
of  the  organism,  a  tolerably  definite  term  of  existence,  and  in  a  like 
manner  die  and  waste  away  when  the  portion  of  work  allotted  to 


FIG.  326.— Coloured  nucleated  corpuscles,  from  the  red  marrow  of  the  guinea-pig. 
(E.  A.  Schiifer.) 

them  has  been  performed.  Neither  the  length  of  their  life,  however, 
nor  the  fashion  of  their  decay,  has  been  yet  wholly  made  out.  A 
certain  number  of  the  coloured  corpuscles  undergo  disintegration  in 
the  liver  and  spleen ;  corpuscles  in  various  degrees  of  degeneration 
have  been  observed  in  both  these  organs. 

This  being  so,  it  is  necessary  that  the  red  corpuscles  should  be 
constantly  replenished  throughout  life.  But  after  the  festal  stage 
is  passed,  they  originate,  not  from  connective  tissues  in  general,  but 
in  one  special  form  of  connective  tissue,  namely,  the  red  marrow 
of  bones.  It  is  possible  that  in  some  animals  the  spleen,  which 
contains  cells  very  similar  to  those  of  the  marrow,  may  participate 
in  their  formation.  In  the  red  marrow,  they  arise  from  immature 
nucleated  cells  (normoUasts  or  erythroNasts,  fig.  326) ;  the  nucleus  is 
not  discharged,  but  is  absorbed  within  the  cell,  and  this  is  the  explana- 
tion that  some  observers  give  of  the  biconcave  form  of  the  red  disc. 
Sometimes  immature  nucleated  red  cells  may  make  their  way  from 
the  marrow  into  the  circulation ;  and  the  free  nuclei  of  these  cells 
are  sometimes  found  in  the  blood ;  they  never,  when  once  they  have 
entered  the  blood,  develop  into  discs,  and  are  filtered  out  of  the 
blood  by  the  spleen. 


CH.  XXIX.]  CHEMISTRY  OF   BLOOD-CORPUSCLES  461 

Origin  of  the  White  Corpuscles. — The  lymphocytes  are  formed 
in  the  lymphoid  tissue  of  the  lymphatic  glands,  tonsils,  and  other 
parts  where  this  tissue  is  present.  They  enter  the  blood-stream  by 
the  thoracic  duct,  and  grow  larger,  the  proportion  of  protoplasm  to 
nucleus  increasing  as  they  become  mature.  The  mononuclear  leuco- 
cyte is,  according  to  some,  a  mature  lymphocyte ;  some  think  it 
is  endothelial  in  origin  (see  p.  456);  according  to  others,  it,  like  the 
polynuclear  leucocytes,  originates  from  immature  forms  in  the  red 
marrow,  which  are  called  myelocytes.  The  leucocytes  proper,  as 
distinguished  from  the  lymphocytes,  do  not  grow  larger  in  the  blood- 
stream, but  rather  have  a  tendency  to  shrink  in  size  with  age. 

If  immature  myelocytes  escape  from  the  marrow  into  the  circu- 
lating blood,  they  undergo  no  further  development  there,  and  like 
the  immature  nucleated  red  corpuscles,  are  filtered  off  by  the  spleen. 
This,  of  course,  is  a  pathological  condition,  and  leads  to  the  swelling 
of  the  spleen,  which  is  such  a  marked  feature  in  the  disease  known 
as  splenic  leukaemia. 

Chemistry  of  the  Blood- Corpuscles. 

The  white  blood-corpuscles. — Their  nucleus  consists  of  nuclein, 
their  cell  protoplasm  yields  proteins  belonging  to  the  globulin  and 
nucleo-protein  groups.  The  protoplasm  of  these  cells  often  contains 
small  quantities  of  fat  and  glycogen. 

The  red  blood-corpuscles. — 1000  parts  of  red  corpuscles  con- 
tain— 

Water      . 688       parts. 

Solids  /Organic 303-88     „ 

ls  \Inorganic 8'12      „ 

One  hundred  parts  of  the  dry  organic  matter  contain— 

Protein 5  to  12  parts. 

Haemoglobin 86  to  94     „ 

Phosphatides  calculated  as  lecithin       .         .         .         .  1  '8    „ 

Cholesterin O'l    „ 

The  protein  present  appears  to  be  identical  with  the  nucleo-protein 
of  white  corpuscles.  The  mineral  matter  consists  chiefly  of  chlorides 
of  potassium  and  sodium,  and  phosphates  of  calcium  and  magnesium. 
In  man  potassium  chloride  is  more  abundant  than  sodium  chloride ; 
this,  however,  does  not  hold  good  for  all  animals. 

Haemoglobin  and  Oxy haemoglobin. — The  pigment  is  by  far 
the  most  abundant  and  important  of  the  constituents  of  the  red 
corpuscles.  It  is  a  conjugated  protein,  a  compound  of  protein  with 
the  iron-containing  pigment  called  haematin. 

It  exists  in  the  blood  in  two  conditions :  in  arterial  blood  it  is 
combined  loosely  with  oxygen,  is  of  a  bright  red  colour,  and  is  called 


462 


THE   BLOOD 


[CH.  XXIX. 


oxyhaemoglobin ;  the  other  condition  is  the  deoxygenated  or  reduced 
haemoglobin  (better  called  simply  haemoglobin).  This  is  found  in  the 
blood  after  asphyxia.  It  also  occurs  in  all  venous  blood — that  is, 
blood  which  is  returning  to  the  heart  after  it  has  supplied  the 
tissues  with  oxygen.  Venous  blood,  however,  always  contains  a  con- 
siderable quantity  of  oxyhaemoglobin  also.  Haemoglobin  is  the  oxygen - 
carrier  of  the  body,  and  it  may  be  called  a  respiratory  pigment.* 

Crystals  of  oxyhaemoglobin  f  may  be  obtained  with  readiness 
from  the  blood  of  such  animals  as  the  rat,  guinea-pig,  or  dog ;  with 
difficulty  from  other  animals,  such  as  man,  ape,  and  most  of  the 
common  mammals.  The  following  methods  are  the  best : — 

1.  Mix  a  drop  of  defibrinated  blood  of  the  rat  on  a  slide  with 
a  drop  of  water;  put  on  a  cover-glass;  in  a  few  minutes  the  cor- 
puscles are  rendered  colourless, 
and  then  the  oxyhaemoglobin 
crystallises  out  from  the  solution 
so  formed. 

2.  Microscopical    specimens 
may   also   be    made    by   Stein's 
method,  which  consists  in  using 
Canada  balsam  instead  of  water 
in  the  foregoing  experiment. 

3.  On  a  larger  scale,  crystals 
may  be  obtained  by  mixing  the 
blood  with   one-sixteenth  of  its 
volume  of  ether;  the  corpuscles 
dissolve,  and  the  blood  assumes  a 
laky  appearance.    After  a  period 
varying  from  a  few  minutes  to 
days,  abundant  crystals  are  de- 
posited. 

In  nearly  all  animals  the  crystals  are  rhombic  prisms  (fig.  327) ; 
but  in  the  guinea-pig  they  are  rhombic  tetrahedra,  or  four-sided 
pyramids  (fig.  328);  in  the  squirrel  and  hamster,  hexagonal  plates 

^  The  crystals  contain  a  varying  amount  of  water  of  crystallisation  ; 
this  probably  explains  their  different  crystalline  form  and  solubilities. 
Several  observers  have  analysed  haemoglobin.  They  find  carbon, 
hydrogen,  nitrogen,  oxygen,  sulphur,  and  iron.  The  percentage  of 

*  In  the  blood  of  invertebrate  animals  haemoglobin  is  sometimes  found,  but 
usually  in  the  plasma,  not  in  special  corpuscles.  Sometimes  it  is  replaced  by  other 
respiratory  pigments,  such  as  the  green  one,  chlorocruorin,  found  in  certain  worms, 
and  the  blue  one,  haemocyanin,  found  in  many  molluscs  and  Crustacea.  Chloro- 
cruorin contains  iron  ;  haemocyanin  contains  copper. 

t  Crystals  of  haemoglobin  can  also  be  obtained  by  carrying  out  the  crystal- 
lisation in  an  atmosphere  free  from  oxygen. 


FIG.  327. — Crystals  of  oxyhsemoglobin— prismatic, 
from  human  blood. 


CII.  XXIX.] 


DERIVATIVES    OF    HEMOGLOBIN 


463 


iron  is  04.  On  adding  an  acid  or  alkali  to  haemoglobin,  it  is  broken 
up  into  two  parts — a  brown  pigment  called  hcematin,  which  contains 
all  the  iron  of  the  original  substance,  and  a  protein  called  globin. 


FIG.  323. — Oxyhsemoglobin  crystals — tetrahedral, 
from  blood  of  the  guinea-pig. 


FIG.  329.— Hexagonal  oxyhaemoglobin  crystals, 
from  blood  of  squirrel.    (After  Funke.) 


Haematin  is  not  crystallisable ;  it  has  the  formula  C34H3305N4Fe 
or  C34H3505N4Fe ;  its  constitutional  formula  is,  however,  not  known. 
Haematin  presents  different  spectroscopic  appearances  in  acid  and 
alkaline  solutions  (see  accompanying  plate).  On  decomposition  it 
yields  pyrrol  derivatives  (see  small  print,  p.  464). 

Globin  is  coagulable  by  heat,  soluble  in  dilute  acids,  and  pre- 
cipitable  from  such  solutions  by  ammonia.  It  belongs  to  the  class  of 
proteins  called  histones  (see  p.  427). 

Haemochromogen  is  sometimes  called  reduced  haematin ;  it  may 
be  formed  by  adding  a  reducing  agent  such  as  ammonium  sulphide  to 
an  alkaline  solution  of  haematin,  and  has  recently  been  obtained  in 
crystalline  form.  Its  absorption  spectrum,  shown  on  the  accompany- 
ing plate  (No.  8),  forms  the  best  spectroscopic  test  for  blood  pigment ; 
the  suspected  pigment  is  dissolved  in  potash,  and  ammonium  sulphide 
added.  Very  dilute  specimens  show  the  absorption  bands,  especially 
the  one  midway  between  D  and  E. 

Haemin  is  of  great  importance,  as  the  obtaining  of  this  substance 
forms  the  best  chemical  test  for  blood.  Haemin  crystals  may  be  pre- 
pared for  microscopical  examination  by  boiling  a  fragment  of  dried 
blood  with  a  drop  of  glacial  acetic  acid  on  a  slide ;  on  cooling,  triclinic 
plates  and  prisms  of  a  dark  brown  colour,  often  in  star-shaped 
clusters  and  with  rounded  angles  (fig.  330),  separate  out.  In  the 
case  of  an  old  blood-stain  it  is  necessary  to  add  a  crystal  of  sodium 
chloride.  Fresh  blood  contains  sufficient  sodium  chloride  in  itself. 

The  action  of  the  acetic  acid  is  to   split  the   haemoglobin  into 


464  THE   BLOOD  [CFl.  XXIX. 

haematin  and  globin;  a  hydroxyl  group  of  the  hsematin  is  then 
replaced  by  chlorine;  it  is  similarly  easily  replaceable  by  an  atom 
of  bromine  or  iodine.  Nencki  and  Zaleski  have  further  shown  that 
when  prepared  in  this  way,  hsemin  also  contains  an  acetyl  group. 
It  has  the  empirical  formula  C34H32or3404N4FeCl. 

Hsematoporphyrin,  C34H3806N4,  is  iron-free  haematin ;  it  may  be 
prepared  by  mixing  blood  with  strong  sulphuric  acid ;  the  iron  is 
taken  out  as  ferrous  sulphate.  It  is  also  found  sometimes  in  nature ; 


FIG.  330.— Hsemin  crystals.    (Frey.)  FIG.  331.— Hsematoidin  crystals. 

(Frey.) 

it  occurs  in  certain  invertebrate  pigments,  and  may  also  be  found  in 
certain  forms  of  pathological  urine.  Even  normal  urine  contains 
traces  of  it.  It  presents  different  spectroscopic  appearances  accord- 
ing as  it  is  dissolved  in  acid  or  alkaline  media.  The  absorption 
spectrum  figured  (No.  9)  is  that  of  acid  haematoporphyrin. 

If  oxyhaemoglobin  is  treated  with  dilute  acids  the  result  is  a  formation  of 
haematin  and  globin,  but  if  strong  sulphuric  acid  is  employed  the  iron  is  removed 
from  the  haematin  and  so  haematoporphyrin  is  obtained.  The  stability  of  the  iron 
in  the  molecule  is  due  to  the  presence  of  oxygen,  for  with  the  reduced  pigment, 
haematoporphyrin  is  obtained  even  when  dilute  acids  are  employed.  Pure  haemato- 
porphyrin  can  once  more  be  converted  into  haematin  (that  is,  the  iron  can  be  replaced) 
by  warming  a  solution  in  dilute  ammonia  and  adding  a  little  Stokes'  fluid,  and  a  few 
drops  of  a  reducing  agent  such  as  hydrazine  hydrate.  If  cuprammonium  solution  is 
used  instead  of  Stokes'  fluid  in  this  experiment,  a  copper  compound  of  haemato- 
porphyrin is  obtained,  which  is  identical  with  turacin,  the  bright  red  copper-containing 
pigment  found  in  the  plumage  of  the  plantain-eating  birds.  (Laidlaw.) 

Hcemopyrrol  is  a  substance  obtained  by  reduction  from  haematoporphyrin.     It 
is  dimethyl-ethyl  pyrrol,  and  its  formula  is  : — 


CH3.C 
CH3.C 


C.C2H5 


CH 


1STH 


There  is  a  near  relationship  between  haemoglobin  and  chlorophyll,  for 
the  same  substance  is  obtained  from  phylloporphyrin,  C16H18N.X),  a  derivative  of 
chlorophyll.  Chlorophyll,  however,  contains  no  iron. 

Haematoidin. — This  substance  is  found  in  the  form  of  yellowish 
red  crystals  (fig.  331)  in  old  blood  extravasations,  and  is  derived  from 
the  haemoglobin.  Its  crystalline  form  and  the  reaction  it  gives  with 


CH.  XXIX.]  COMPOUNDS   OF   HEMOGLOBIN  465 

fuming  nitric  acid  show  it  to  be  closely  allied  to  bilirubin,  the  chief 
colouring  matter  of  the  bile,  and  on  analysis  it  is  found  to  be  identical 
with  it. 

Haematoidin,  like  haematoporphyrin,  is  free  from  iron,  but  differs 
from  it  in  showing  no  spectroscopic  bands. 

Compounds  of  Haemoglobin. 

Haemoglobin  forms  at  least  four  compounds  with  gases  :  — 


oxygen 

With  carbonic  oxide  .         .        .         .3.  Carbonic  oxide  haemoglobin. 
With  nitric  oxide       .         .        .         .4.  Nitric  oxide  haemoglobin. 

These  compounds  have  similar  crystalline  forms;  they  each 
consist  of  a  molecule  of  haemoglobin  combined  with  one  of  the  gas  in 
question  (see  p.  366).  They  part  with  the  combined  gas  somewhat 
readily  ;  they  are  arranged  in  order  of  stability  in  the  above  list,  the 
least  stable  first. 

Oxyhaemoglobin  is  the  compound  that  exists  in  arterial  blood. 
Many  of  its  properties  have  been  already  mentioned.  The  oxygen 
linked  to  the  haemoglobin,  which  is  removed  by  the  tissues  through 
which  the  blood  circulates,  may  be  called  the  respiratory  oxygen  of 
haemoglobin.  The  processes  that  occur  in  the  lungs  and  tissues, 
resulting  in  the  oxygenation  and  deoxygenation  respectively  of  the 
haemoglobin,  may  be  imitated  outside  the  body,  using  either  blood  or 
pure  solutions  of  haemoglobin.  The  respiratory  oxygen  can  be 
removed,  for  example,  in  the  Torricellian  vacuum  of  a  mercurial  air- 
pump,  or  by  passing  a  neutral  gas  such  as  hydrogen  through  the  blood, 
or  by  the  use  of  reducing  agents  such  as  ammonium  sulphide  and 
Stokes'  reagent.*  One  gramme  of  haemoglobin  will  combine  with 
1*34  c.c.  of  oxygen. 

If  any  of  these  methods  for  reducing  oxyhaemoglobin  is  used,  the 
bright  red  (arterial)  colour  of  oxyhaemoglobin  changes  to  the  darker 
(venous)  tint  of  haemoglobin.  On  once  more  allowing  oxygen  to 
come  into  contact  with  the  haemoglobin,  as  by  shaking  the  solution 
with  the  air,  the  bright  arterial  colour  returns. 

These  colour-changes  may  be  more  accurately  studied  with  the 
spectroscope,  and  the  constant  position  of  the  absorption  bands  seen 
constitutes  an  important  test  for  blood  pigment.  It  will  be  first 
necessary  to  describe  briefly  the  instrument  used. 

The  Spectroscope.  —  When  a  ray  of  white  light  is  passed  through 
a  prism,  it  is  refracted  or  bent  at  each  surface  of  the  prism;  the 

*  Stokes'  reagent  must  always  be  freshly  prepared  ;  it  is  a  solution  of  ferrous 
sulphate  to  which  a  little  tartaric  acid  has  been  added,  and  then  ammonia  till  the 
reaction  is  alkaline. 

2  G 


466  THE   BLOOD  [CH.  XXIX. 

whole  ray  is,  however,  not  equally  bent,  but  it  is  split  into  its 
constituent  colours,  which  may  be  allowed  to  fall  on  a  screen.  The 
band  of  colours  beginning  with  the  red,  passing  through  orange, 
yellow,  green,  blue,  and  ending  with  violet,  is  called  a  spectrum :  this 
is  seen  in  nature  in  the  rainbow. 

The  spectrum  of  sunlight  is  interrupted  by  numerous  dark  lines 
crossing  it  vertically,  called  Frauenhofer's  lines.  These  are  perfectly 
constant  in  position  and  serve  as  landmarks  in  the  spectrum.  The 
more  prominent  are  A,  B,  and  C,  in  the  red ;  D,  in  the  yellow ;  E,  I, 
and  F,  in  the  green ;  G  and  H,  in  the  violet.  These  lines  are  due  to 
certain  volatile  substances  in  the  solar  atmosphere.  If  the  light 
from  burning  sodium  or  its  compounds  is  examined  spectroscopically, 
it  will  be  found  to  give  a  bright  yellow  line,  or,  rather,  two  bright 
yellow  lines  very  close  together.  Potassium  gives  two  bright  red 
lines  and  one  violet  line ;  and  the  other  elements,  when  incandescent, 
give  characteristic  lines,  but  none  so  simple  as  sodium.  If  now  the 
flame  of  a  lamp  is  examined,  it  will  be  found  to  give  a  continuous 
spectrum  like  that  of  sunlight  in  the  arrangement  of  its  colours,  but 
unlike  it  in  the  absence  of  dark  lines ;  but  if  the  light  from  the  lamp 
is  made  to  pass  through  sodium  vapour  before  it  reaches  the  spectro- 
scope, the  bright  yellow  light  will  be  found  absent,  and  in  its  place  a 
dark  line,  or,  rather,  two  dark  lines  very  close  together,  occupying 
the  same  position  as  the  two  bright  lines  of  the  sodium  spectrum. 
The  sodium  vapour  absorbs  the  same  rays  as  those  which  it  itself 
produces  at  a  higher  temperature.  Thus  the  D  line,  as  we  term  it  in 
the  solar  spectrum,  is  due  to  the  presence  of  sodium  vapour  in  the 
solar  atmosphere.  The  other  dark  lines  are  similarly  accounted  for 
by  other  elements. 

The  large  form  of  spectroscope  (fig.  332)  consists  of  a  tube 
A,  called  the  collimator,  with  a  slit  at  the  end  S,  and  a  convex 
lens  at  the  end  L.  The  latter  makes  the  rays  of  light  passing 
through  the  slit  from  the  source  of  light,  parallel:  they  fall  on 
the  prism  P,  and  then  the  spectrum  so  formed  is  focussed  by  the 
telescope  T. 

A  third  tube,  not  shown  in  the  figure,  carries  a  small  transparent 
scale  of  wave-lengths,  as  in  accurate  observations  the  position  of  any 
point  in  the  spectrum  is  given  in  the  terms  of  the  corresponding 
wave-lengths. 

If  we  now  interpose  between  the  source  of  light  and  the  slit  S  a 
piece  of  coloured  glass  (H  in  fig.  333),  or  a  solution  of  a  coloured 
substance  contained  in  a  vessel  with  parallel  sides  (the  haematoscope 
of  Herrmann),  the  spectrum  is  found  to  be  no  longer  continuous,  but 
is  interrupted  by  a  number  of  dark  shadows,  or  absorption  lands 
corresponding  to  the  light  absorbed  by  the  coloured  medium.  Thus  a 
solution  of  oxyhaemoglobin  of  a  certain  strength  gives  two  bands 


BLOOD-SPECTRA  COMPARED  WITH  SOLAR  SPECTRUM, 


1.  Solar  spectrum. 

2.  Spectrum  of  dilute  solution  of  oxyhaemoglobin, 

„    haemoglobin. 

„    carbonic  oxide  haemoglobin. 

„    acid  haematin  in  ethereal  solution. 

,,   alkaline  haematin. 

,,    methaemoglobin . 

,,    haemochromogen. 

,,    acid  haematoporphyrin. 


[To  face  page  466. 


CH.  XXIX.]  THE   SPECTROSCOPE  467 

between  the  D  and  E  lines ;  haemoglobin  gives  only  one ;  and  other 
red  solutions,  though  to  the  naked  eye  similar  to  oxyhaemoglobin,  will 
give  characteristic  bands  in  other  positions. 

A   convenient   form   of   small   spectroscope   is  the  direct  vision 
spectroscope,  in  which,  by  an  arrangement  of  alternating  prisms  of 


FIG.  332.— Diagram  of  Spectroscope. 

crown  and  flint  glass,  the  spectrum  is  observed  by  the  eye  in  the 
same  line  as  the  tube  furnished  with  the  slit — indeed,  slit  and  prisms 
are  both  contained  in  the  same  tube. 

In  the  examination  of  the  spectrum  of  small  coloured  objects  a 
combination  of  the  microscope  and  direct  vision  spectroscope,  called  the 
micro-spectroscope,  is  used. 

The  next  figure  (fig.  333)  illustrates  a  method  of  representing 
absorption  spectra  diagrammatically.  The  solution  was  examined 
in  a  layer  1  centimetre  thick.  The  base-line  has  on  it  at  the  proper 
distances  the  chief  Frauenhofer  lines,  and  along  the  right-hand  edges 
are  percentages  of  the  amount  of  oxyhaemoglobin  present  in  I,  of 
haemoglobin  in  II.  The  width  of  the  shadings  at  each  level  repre- 
sents the  position  and  amount  of  absorption  corresponding  to  the 
percentages. 

The  characteristic  spectrum  of  oxyhaemoglobin,  as  it  actually 
appears  through  the  spectroscope,  is  seen  in  the  accompanying 
coloured  plate  (spectrum  2).  There  are  two  distinct  absorption 
bands  between  the  D  and  E  lines;  the  one  nearest  to  D  (the  a 
band)  is  narrower,  darker,  and  has  better-defined  edges  than  the 
other  (the  /3  band).  As  will  be  seen  on  looking  at  fig.  333,  a  solution 
of  oxyhaemoglobin  of  concentration  greater  than  0*65  per  cent,  and 
less  than  0'85  per  cent,  (examined  in  a  cell  of  the  usual  thickness  of 
1  centimetre)  gives  one  thick  band  overlapping  both  D  aijd  E,  and  a 
stronger  solution  only  lets  the  red  light  through  between  C  and  D. 
A  solution  which  gives  the  two  characteristic  bands  must  therefore  be 
a  dilute  one.  The  one  band  (y  band)  of  haemoglobin  (spectrum  3)  is 


468 


THE   BLOOD 


[CH.  XXIX. 


not  so  well  defined  as  the  a  or  0  bands.     On  dilution  it  fades  rapidly  ; 
so  that  in  a  solution  of  such  strength  that  both  bands  of  oxyhsemoglobm 


ABC 


Fio  333  -Graphic  representations  of  the  amount  of  absorption  of  light  by  solution  of  (1)  oxyhsemo- 
'globin,  (II)  of  hemoglobin,  of  different  strengths.  The  shading  indicates  the  amount  of  absorption 
of  the  spectrum  ;  the  figures  on  the  right  border  express  percentages.  (Rollett.) 

would  be  quite  distinct,  the  single  band  of  haemoglobin  has  disappeared 
from  view.  The  oxyhaemoglobin  bands  can  be  distinguished  in  a 
solution  which  contains  only  one  part  of  the  pigment  to  10,000  of 
water,  and  even  in  more  dilute  solutions  which  seem  to  be  colourless 
the  a  band  is  still  visible. 


A    HK   L    M       isj 


FIG.  334.— The  photographic  spectrum  of  haemoglobin  and  oxy haemoglobin.    (Gamgee.) 

Haemoglobin  and  its  compounds  also  show  absorption  bands  in 
the  ultra-violet  portion  of  the  spectrum.     This  portion  of  the  spectrum 


CH.  XXIX.]  THE   PHOTOGRAPHIC    SPECTRUM  469 

is  not  visible  to  the  eye,  but  can  be  rendered  visible  by  allowing  the 
spectrum  to  fall  on  a  fluorescent  screen,  or  on  a  sensitive  photographic 
plate.  In  order  to  show  absorption  bands  in  this  part  of  the  spectrum 
very  dilute  solutions  of  the  pigment  must  be  used. 

Oxyhaemoglobin  shows  a  band  (Soret's  band)  between  the  lines  G 
and  H.     In  haemoglobin,  carbonic  oxide  haemoglobin,  and  nitric  oxide 


FIG.  335.— The  photographic  spectrum  of  oxyluerooglobin  and  methsemoglobin.    (Gamgee.) 

haemoglobin,  this  band  is  rather  nearer  G-.  Methaemoglobin  and 
haematoporphyrin  show  similar  bands. 

We  owe  most  of  our  knowledge  of  the  "  photographic  spectrum  " 
to  the  late  Prof.  Gamgee,  through  whose  kindness  I  am  enabled  to 
present  reproductions  of  two  of  his  numerous  photographs  (figs. 
334  and  335). 

Methsemoglobin. — This  may  be  produced  artificially  in  various 
ways,  as  by  adding  potassium  ferricyanide  or  amyl  nitrite  to  blood, 
and  as  it  also  may  occur  in  certain  diseased  conditions  in  the  urine, 
it  is  of  considerable  practical  importance.  It  can  be  crystallised,  and 
is  found  to  contain  the  same  amount  of  oxygen  as  oxyhaemoglobin, 
only  combined  in  a  different  way.  The  oxygen  is  not  removable  by 
the  air-pump,  nor  by  a  stream  of  neutral  gas  such  as  hydrogen.  It 
can,  however,  by  reducing  agents  like  ammonium  sulphide,  be  made  to 
yield  haemoglobin.  Methaemoglobin  is  of  a  brownish  red  colour,  and 
gives  a  characteristic  absorption  band  in  the  red  between  the  C  and 
D  lines  (spectrum  7  in  coloured  plate).  In  dilute  solutions  other 
bands  can  be  seen. 

Potassium  ferricyanide  is  the  most  convenient  reagent  for  making  methaemo- 
globin.  It  is,  however,  necessary  to  remind  the  reader  that  it  produces  another 
effect  as  well,  namely,  it  causes  an  evolution  of  gas,  if  the  blood  has  been  previ- 
ously laked.  This  gas  is  oxygen  ;  in  fact,  all  the  oxygen  combined  as  oxyhanno- 


470  THE   BLOOD  [CH.  XXIX. 

globin  is  discharged,  and  this  may  be  collected  and  measured  as  in  the  method 
described  on  p.  364.  This  discharge  of  oxygen  from  oxy haemoglobin  is  at  first 
sight  puzzling,  because,  as  just  stated,  methaemoglobin  contains  the  same  amount 
of  oxygen  that  is  present  in  oxyhaemoglobin.  What  occurs  is  that  after  the  oxygen 
is  discharged  from  oxyhaemoglobin,  an  equal  quantity  of  oxygen,  due  to  the 
oxidising  action  of  the  reagents  added,  takes  its  place ;  this  new  oxygen,  how- 
ever, is  combined  in  some  way  different  from  that  which  was  previously  united 
to  the  haemoglobin.  (Haldane.) 

Carbonic  oxide  haemoglobin  may  be  readily  prepared  by  passing 
a  stream  of  carbonic  oxide  or  coal  gas  through  blood  or  through  a 
solution  of  oxyhaemoglobin.  It  has  a  peculiar  cherry-red  colour.  Its 
absorption  spectrum  is  very  like  that  of  oxyhaemoglobin,  but  the  two 
bands  are  slightly  nearer  the  violet  end  of  the  spectrum  (spectrum  4 
in  coloured  plate).  Seducing  agents,  such  as  ammonium  sulphide,  do 
not  change  it ;  the  gas  is  more  firmly  combined  than  the  oxygen  in 
haemoglobin.  CO -haemoglobin  forms  crystals  like  those  of  oxyhaemo- 
globin. It  resists  putrefaction  for  a  very  long  time. 

Carbonic  oxide  is  given  off  during  the  imperfect  combustion  of 
carbon  such  as  occurs  in  charcoal  stoves  or  during  the  explosions  that 
occur  in  coal-mines ;  it  acts  as  a  powerful  poison,  by  combining  with 
the  haemoglobin  of  the  blood,  and  thus  interferes  with  normal  respira- 
tory processes.  The  bright  colour  of  the  blood  in  both  arteries  and 
veins,  and  its  resistance  to  reducing-agents,  are  in  such  cases 
characteristic. 

Nitric  Oxide  Haemoglobin. — When  ammonia  is  added  to  blood, 
and  then  a  stream  of  nitric  oxide  passed  through  it,  this  compound 
is  formed.  It  may  be  obtained  in  crystals  isomorphous  with  oxy- 
and  CO-haemogloljin.  It  also  has  a  similar  spectrum.  It  is  even 
more  stable  than  CO-haemoglobin  ;  it  has  no  practical  interest,  but  is 
of  theoretical  importance  as  completing  the  series. 

Estimation  of  Haemoglobin. — The  most  exact  method  is  by  the  estimation  of 
the  amount  of  iron  (dry  haemoglobin  containing  "42  per  cent,  of  iron)  in  the  ash  of  a 
given  specimen  of  blood,  but  as  this  is  a  somewhat  complicated  process,  various 
coloriraetric  methods  have  been  proposed  which,  though  not  so  exact,  have  the 
advantage  of  simplicity. 

Gowers'  Hsemoglobinometer. — The  apparatus  (fig.  336)  consists  of  two  glass 
tubes  of  the  same  size.  One  contains  glycerin  jelly  tinted  with  carmine  to  a 
standard  colour— viz.,  that  of  normal  blood  diluted  100  times  with  distilled  water. 
The  finger  is  pricked  and  20  cubic  millimetres  of  blood  are  measured  out  by  the 
capillary  pipette  B.  This  is  blown  out  into  the  other  tube  and  diluted  with  distilled 
water,  added  drop  by  drop  from  the  pipette  stopper  of  the  bottle  A,  until  the  tint 
of  the  diluted  blood  reaches  the  standard  colour.  This  tube  is  graduated  into  100 
parts.  If  the  tint  of  the  diluted  blood  is  the  same  as  the  standard  when  the  tube  is 
filled  up  to  the  graduation  100,  the  quantity  of  oxyhaemoglobin  in  the  blood  is 
normal.  If  it  has  to  be  diluted  more  largely,  the  oxyhaemoglobin  is  in  excess  ;  if  to 
a  smaller  extent,  it  is  less  than  normal.  If  the  blood  has,  for  instance,  to  be  diluted 
up  to  the  graduation  50,  the  amount  of  haemoglobin  is  only  half  what  it  ought  to 
be— 50  per  cent,  of  the  normal— and  so  for  other  percentages. 

Haldane's  Modification  of  Gowers'  Instrument  is  the  one  most  frequently 
used  now,  and  gives  very  accurate  results.  Instead  of  tinted  gelatin,  the  standard 
of  comparison  is  a  sealed  tube  filled  with  a  solution  of  carbonic  oxide  haemoglobin. 


en.  xxix.] 


H^EMOGLOBINOMETERS 


471 


This  keeps  unchanged  for  years.  A  stream  of  coal  gas  is  passed  through  the  blood 
to  be  examined.  This  converts  all  the  haemoglobin  present  into  carbonic  oxide 
haemoglobin ;  this  is  then  diluted  with  water  to  match  the  standard. 


FIG.  336. — Hsemoglobinometer  of  Dr  Gowers. 

Von  Fleischl's  Haemometer. — The  apparatus  (fig.  337)  consists   of  a  stand 
bearing  a  white  reflecting  surface  (S)  and  a  platform.     Under  the  platform  is  a  slot 


Fia.  337. — Von  Fleischl's  Htemoglobinometer. 


carrying  a  glass  wedge  stained  red  (K)  and  moved  by  a  wheel  (R).     On  the  platform 
is  a  small  cylindrical  vessel  divided  vertically  into  two  compartments,  a  and  a'» 


472  THE   BLOOD  [CH.  XXIX. 

Fill  with  a  pipette  the  compartment  a'  over  the  wedge  with  distilled  water. 
Fill  about  a  quarter  of  the  other  compartment  (a)  with  distilled  water. 

Prick  the  finger  and  fill  the  short  capillary  pipette  provided  with  the  instru- 
ment with  blood.  Dissolve  this  in  the  water  in  compartment  a,  and  fill  it  up  with 
distilled  water. 

Having  arranged  the  reflector  (S)  to  throw  artificial  light  vertically  through 
both  compartments,  look  down  through  them,  and  move  the  wedge  of  glass  by  the 
milled  head  (T)  until  the  colour  of  the  two  is  identical.  Read  off  the  scale,  which  is 
so  constructed  as  to  give  the  percentage  of  haemoglobin. 

Dr  George  Oliver's  Method  consists  in  comparing  a  specimen  of  blood 
suitably  diluted  in  a  shallow  white  palette  with  a  number  of  standard  tests  very 
carefully  prepared  by  the  use  of  Lovibond's  coloured  glasses.  These  standards  are 
much  better  matches  for  blood  in  various  degrees  of  dilution  than  in  most  colori- 
metric  methods.  The  yellow  tint  of  diluted  haemoglobin  is  very  successfully 
imitated. 

Tests  for  Blood. — These  may  be  gathered  from  preceding  descrip- 
tions. Briefly,  they  are  microscopic,  spectroscopic,  and  chemical. 
The  best  chemical  test  is  the  formation  of  haemin  crystals.  The  old 
test  with  tincture  of  guaiacum  and  hydrogen  peroxide,  the  blood 
causing  the  tincture  to  become  bluish  green,  is  very  untrustworthy, 
as  it  is  also  given  by  many  other  organic  substances.  The  test, 
for  instance,  is  given  by  milk,  and  is  there  due  to  the  presence 
of  an  enzyme  called  a  peroxidase,  which  is  destroyed  by  boiling. 
Boiled  blood,  however,  gives  the  test  as  well  as  fresh  blood,  and  the 
reaction  is  due  to  the  presence  of  the  iron-containing  radical  of 
haemoglobin. 

In  medico-legal  cases  it  is  often  necessary  to  ascertain  whether  or 
not  a  red  fluid  or  stain  upon  clothing  is  of  blood.  In  any  such 
case  it  is  advisable  not  to  rely  upon  one  test  only,  but  to  try  every 
means  of  detection  at  one's  disposal.  To  discover  whether  it  is  blood 
or  not  is  by  no  means  a  difficult  problem,  but  to  distinguish  human 
blood  from  that  of  the  common  mammals  is  possible  only  by  the 
"  biological "  test  described  at  the  end  of  the  next  section. 

Immunity. 

The  chemical  defences  of  the  body  against  injury  and  disease  are 
numerous.  The  property  that  the  blood  possesses  of  coagulating  is 
a  defence  against  haemorrhage ;  the  acid  of  the  gastric  juice  is  a  great 
protection  against  harmful  bacteria  introduced  with  food.  Bacterial 
activity  in  urine  is  inhibited  by  the  acidity  of  that  secretion. 

Far  more  important  and  widespread  in  its  effects  than  any  of  the 
foregoing  is  the  bactericidal  (i.e.  bacteria -killing)  action  of  the  blood 
and  lymph;  a  study  of  this  question  has  led  to  many  interesting 
results^  especially  in  connection  with  the  problem  of  immunity. 

It  is  a  familiar  fact  that  one  attack  of  many  infective  maladies 
protects  us  against  another  attack  of  the  same  disease.  The  person 
is  said  to  be  immune  either  partially  or  completely  against  that 


CH.  XXIX.]  IMMUNITY  473 

disease.  Vaccination  produces  in  a  patient  an  attack  of  cowpox  or 
vaccinia.  This  disease  is  either  closely  related  to  smallpox,  or 
maybe  it  is  smallpox  modified  and  rendered  less  malignant  by  passing 
through  the  body  of  a  calf.  At  any  rate,  an  attack  of  vaccinia  renders 
a  person  immune  to  smallpox,  or  variola,  for  a  certain  number  of 
years.  Vaccination  is  an  instance  of  what  is  called  protective  inoculation, 
which  is  now  practised  with  more  or  less  success  in  reference  to  other 
diseases,  such  as  plague  and  typhoid  fever.  The  study  of  immunity 
has  also  rendered  possible  what  may  be  called  curative  inoculation,  or 
the  injection  of  antitoxic  material  as  a  cure  for  diphtheria,  tetanus, 
snake-poisoning,  etc. 

The  leucocytes  or  phagocytes  destroy  bacteria  by  feeding  on 
them ;  but  the  fluid  part  of  the  blood  is  often  antagonistic  to  bacterial 
life,  and  this  power  was  first  discovered  when  the  effort  was  made  to 
grow  various  kinds  of  bacteria  in  it ;  it  was  looked  upon  as  probable 
that  blood-serum  would  prove  a  suitable  soil  or  medium  for  this 
purpose.  It  was  found  in  some  instances  to  have  exactly  the 
opposite  effect.  The  chemical  characters  of  the  substances  which  kill 
the  bacteria  are  not  fully  known ;  indeed,  the  same  is  true  for  most 
of  the  substances  we  have  to  speak  of  in  this  connection.  Absence 
of  knowledge  on  this  particular  point  has  not,  however,  prevented 
important  practical  discoveries  from  being  made. 

So  far  as  is  known  at  present,  the  substances  in  question  are 
protein  in  nature.  The  bactericidal  powers  of  blood  are  destroyed  by 
heating  it  for  an  hour  to  55°  C.  Whether  the  substances  are  derived 
from  the  leucocytes  is  a  disputed  point.  The  substances,  whatever 
be  their  source  or  their  chemical  nature,  are  called  lacterio-lysins. 

Closely  allied  to  the  bactericidal  power  of  blood,  or  blood-serum, 
is  its  globulicidal  power.  By  this  one  means  that  the  blood-serum  of 
one  animal  has  the  power  of  dissolving  the  red  blood-corpuscles  of 
another  species.  If  the  serum  of  one  animal  is  injected  into  the 
blood-stream  of  an  animal  of  another  species,  the  result  is  a  destruction 
of  its  red  corpuscles,  which  may  be  so  excessive  as  to  lead  to  the 
passing  of  the  liberated  haemoglobin  into  the  urine  (haemoglobinuria). 
The  substance  or  substances  in  the  serum  that  possess  this  property 
are  called  hcemolysins,  and  though  there  is  some  doubt  whether 
bacterio-lysins  and  haemolysins  are  absolutely  identical,  there  is  no 
doubt  that  they  are  closely  related  substances. 

Normal  blood  possesses  a  certain  amount  of  substances  which  are 
inimical  to  the  life  of  our  bacterial  foes.  But  suppose  a  person  gets 
run  down ;  every  one  knows  he  is  then  liable  to  "  catch  anything." 
This  coincides  with  a  diminution  in  the  bactericidal  power  of  his 
blood.  But  even  a  perfectly  healthy  person  has  not  an  unlimited 
supply  of  bacterio-lysin,  and  if  the  bacteria  are  sufficiently  numerous 
he  will  fall  a  victim  to  the  disease  they  produce.  Here,  however, 


474  THE   BLOOD  [CH.  XXIX. 

comes  in  the  remarkable  part  of  the  defence.  In  the  struggle  he 
will  produce  more  and  more  bacterio-lysin,  and  if  he  gets  well  it 
means  that  the  bacteria  are  finally  vanquished,  and  his  blood  remains 
rich  in  the  particular  bacterio-lysin  he  has  produced,  and  so  will 
render  him  immune  for  a  time  to  further  attacks  from  that  particular 
species  of  bacterium.  Each  bacterium  attacked  in  this  way  seems  to 
cause  the  development  of  a  specific  anti-substance. 

Immunity  can  more  conveniently  be  produced  gradually  in  animals, 
and  this  applies,  not  only  to  the  bacteria,  but  in  certain  cases  to  the 
toxins  they  form.  If,  for  instance,  the  bacilli  which  produce 
diphtheria  are  grown  in  a  suitable  medium,  they  produce  the 
diphtheria  poison,  or  toxin,  much  in  the  same  way  that  yeast-cells 
will  produce  alcohol  when  grown  in  a  solution  of  sugar.  Diphtheria 
toxin  is  associated  with  a  proteose,  as  is  also  the  case  with  the  poison 
of  snake-venom.  If  a  certain  small  dose  called  a  "lethal  dose"  is 
injected  into  a  guinea-pig  the  result  is  death.  But  if  the  guinea-pig 
receives  a  smaller  dose  it  will  recover ;  a  few  days  after  it  will  stand 
a  rather  larger  dose ;  and  this  may  be  continued  until,  after  many 
successive  gradually  increasing  doses,  it  will  finally  stand  an  amount 
equal  to  many  lethal  doses  without  any  ill  effects.  The  gradual 
introduction  of  the  toxin  has  called  forth  the  production  of  an 
antitoxin.  If  this  is  done  in  the  horse  instead  of  the  guinea-pig  the 
production  of  antitoxin  is  still  more  marked,  and  the  serum  obtained 
from  the  blood  of  an  immunised  horse  may  be  used  for  injecting  into 
human  beings  suffering  from  diphtheria,  and  rapidly  cures  the  disease. 
The  two  actions  of  the  blood,  antitoxic  and  antibacterial,  are  fre- 
quently associated,  but  may  be  entirely  distinct. 

The  antitoxin  is  also  a  protein  probably  of  the  nature  of  a  globulin ; 
at  any  rate  it  is  a  protein  of  larger  molecular  weight  than  a  proteose. 
This  suggests  a  practical  point.  In  the  case  of  snake-poisoning  the 
poison  gets  into  the  blood  rapidly  owing  to  the  comparative  ease  with 
which  it  diffuses,  and  so  it  is  quickly  carried  all  over  the  body.  In 
treatment  with  the  antitoxin  or  antivenin,  speed  is  everything  if  life 
is  to  be  saved ;  injection  of  this  material  under  the  skin  is  not  much 
good,  for  the  diffusion  into  the  blood  is  too  slow.  It  should  be 
injected  straight  away  into  a  blood-vessel. 

There  is  no  doubt  that  in  these  cases  the  antitoxin  neutralises  the 
toxin  much  in  the  same  way  that  an  acid  neutralises  an  alkali.  If 
the  toxin  and  antitoxin  are  mixed  in  a  test-tube,  and  time  allowed 
for  the  interaction  to  occur,  the  result  is  an  innocuous  mixture.  The 
toxin,  however,  is  merely  neutralised,  not  destroyed;  for  if  the 
mixture  in  the  test-tube  is  heated  to  68°  C.  the  antitoxin  is  coagulated 
and  destroyed,  and  the  toxin  remains  as  poisonous  as  ever. 

Immunity  is  distinguished  into  active  and  passive.  Active  im- 
munity is  produced  by  the  development  of  protective  substances  in 


CH.  XXIX.]  THE  SIDE-CHAIN  THEORY  475 

the  body ;  passive  immunity  by  the  injection  of  a  protective  serum. 
Of  the  two  the  former  is  the  more  permanent. 

Ricin,  the  poisonous  protein  of  castor-oil  seeds,  and  abrin,  that  of  the 
jequirity  bean,  also  produce,  when  gradually  given  to  animals,  an  im- 
munity, due  to  the  production  of  anti-ricin  and  anti-abrin  respectively. 

Ehrlich's  hypothesis  to  explain  such  facts  is  usually  spoken  of  as 
the  side-chain  theory  of  immunity.  He  considers  that  the  toxins  are 
capable  of  uniting  with  the  protoplasm  of  living  cells  by  possessing 
groups  of  atoms  like  those  by  which  nutritive  proteins  are  united  to 
cells  during  normal  assimilation.  He  terms  these  haptophor  groups, 
and  the  groups  to  which  these  are  attached  in  the  cells  he  terms 
receptor  groups.  The  introduction  of  a  toxin  stimulates  an  excessive 
production  of  receptors,  which  are  finally  thrown  out  into  the  circula- 
tion, and  the  free  circulating  receptors  constitute  the  antitoxin.  The 
comparison  of  the  process  to  assimilation  is  justified  by  the  fact  that 
non-toxic  substances  like  milk  or  egg-white  introduced  gradually  by 
successive  doses  into  the  blood-stream  cause  the  formation  of  anti- 
substances  capable  of  coagulating  them. 

Up  to  this  point  I  have  spoken  only  of  the  blood,  but  month  by 
month  workers  are  bringing  forward  evidence  to  show  that  other 
cells  of  the  body  may  by  similar  measures  be  rendered  capable  of 
producing  a  corresponding  protective  mechanism. 

The  substances  which  on  injection  provoke  the  appearance  of 
antidotes  of  this  nature  are  of  protein  or  protein-like  nature ;  they 
are  spoken  of  as  antigens. 

One  further  development  of  the  theory  I  must  mention.  At  least 
two  different  substances  are  necessary  to  render  a  serum  bactericidal 
or  globulicidal.  The  bacterio-lysin  or  haemolysin  consists  of  these 
two  substances.  One  of  these  is  called  the  immune  body,  the  other 
the  complement.  We  may  illustrate  the  use  of  these  terms  by  an 
example.  The  repeated  injection  of  the  blood  of  one  animal  (e.g.,  the 
goat)  into  the  blood  of  another  animal  (e.g.,  a  sheep)  after  a  time 
renders  the  latter  animal  immune  to  further  injections,  and  at  the 
same  time  causes  the  production  of  a  serum  which  dissolves  readily 
the  red  blood-corpuscles  of  the  first  animal.  The  sheep's  serum  is  thus 
hsemolytic  towards  goat's  blood-corpuscles.  This  power  is  destroyed 
by  heating  to  56°  C.  for  half  an  hour,  but  returns  when  the  fresh 
serum  of  any  animal  is  added.  The  specific  immunising  substance 
formed  in  the  sheep  is  called  the  immune  body;  the  enzyme-like 
substance  destroyed  by  heat  is  the  complement.  The  latter  is  not 
specific,  since  it  is  furnished  by  the  blood  of  non-immunised  animals, 
but  it  is  nevertheless  essential  for  haemolysis.  Ehrlich  believes  that 
the  immune  body  has  two  side  groups — one  which  connects  with  the 
receptor  of  the  red  corpuscles,  and  one  which  unites  with  the  hapto- 
phor group  of  the  complement,  and  thus  renders  possible  the  enzyme- 


476  THE   BLOOD  [CH.  XXIX. 

like  action  of  the  complement  on  the  red  corpuscles.  Various 
antibacterial  serums  which  have  not  been  the  success  in  treating 
disease  they  were  expected  to  be,  are  probably  too  poor  in  comple- 
ment, though  they  may  contain  plenty  of  the  immune  body. 

To  put  it  another  way :  the  cell-dissolving  substances  cannot  act 
on  their  object  of  attack  without  an  intermediate  substance  to 
anchor  them  on  to  the  object  in  question.  This  intermediary  sub- 
stance, known  as  the  immune  body  or  amboceptor,  is  specific,  and 
varies  with  the  substance  to  be  attacked  (red  corpuscles,  bacterium, 
toxin,  etc.).  The  complement  may  be  compared  to  a  person  who 
wants  to  unlock  a  door ;  to  do  this  effectively  he  must  be  provided 
with  the  proper  key  (amboceptor  or  immune  body). 

Quite  distinct  from  the  bactericidal,  globulicidal,  and  antitoxic 
properties  of  blood  is  its  agglutinating  action.  This  is  another  result 
of  infection  with  many  kinds  of  bacteria  or  their  toxins.  The  blood 
acquires  the  property  of  rendering  immobile  and  clumping  together 
the  specific  bacteria  used  in  the  infection.  The  test  applied  to  the 
blood  in  cases  of  typhoid  fever,  and  generally  called  Widal's  reaction, 
depends  on  this  fact.  The  substances  that  produce  this  effect  are 
called  agglutinins.  They  also  are  probably  protein-like  in  nature, 
but  are  more  resistant  to  heat  than  the  lysins.  Prolonged  heating 
to  over  60°  C.  is  necessary  to  destroy  their  activity. 

We  thus  see  that  the  means  of  combating  our  bacterial  enemies 
are  various;  in  some  cases  they  are  rendered  immobile  by  agglu- 
tinins,  and  in  other  cases,  killed  by  bacterio-lysins.  In  other 
instances,  their  toxins  are  neutralised  by  antitoxins,  and  in  others 
again  they  are  directly  devoured  by  phagocytes.  Metschnikoff's 
view,  which  is  shared  by  many  eminent  bacteriologists,  is  that 
phagocytosis  is  the  supreme  method,  and  the  others  are  merely 
auxiliaries,  or  confined  to  a  small  number  of  cases.  If  a  foreign 
organism  is  destroyed  by  the  leucocytes,  it  produces  no  ill  effects 
when  it  enters  the  body  of  a  man  or  other  animal ;  but  if  it  is  not 
destroyed,  it  grows  and  produces  a  disease,  and  it  is  therefore  called 
pathogenic.  If  the  phagocytes  can  be  induced  to  feed  on  a  patho- 
genic organism,  it  is  at  once  rendered  non-pathogenic.  The  recent 
discovery  of  opsonins,  by  Sir  A.  E.  Wright,  emphasises  this  view  and 
shows  one  means  the  body  possesses  of  persuading  the  leucocytes  to 
eat  bacteria,  which  would  otherwise  be  distasteful  to  them.  Washed 
bacteria  from  a  culture  are  usually  refused  by  leucocytes ;  but  if  the 
bacteria  had  been  previously  soaked  in  serum,  especially  if  that 
serum  has  been  obtained  from  the  blood  of  an  animal  previously 
immunised  against  that  special  bacterium,  then  the  leucocytes 
devour  them  eagerly.  Something  has  either  been  added  to  the 
bacterium  to  make  it  tasty,  or  something  removed  from  it  which 
previously  made  it  distasteful :  whichever  is  the  case,  the  action  is 


CH.  XXIX.]  OPSONINS   AND   PRECIPITINS  477 

described  as  the  action  of  an  opsonin  (derived  from  a  Greek  word 
which  means  "  to  prepare  the  feast "  ). 

We  may  take  the  specific  case  of  the  tubercle  bacillus  as  an 
instance  where  such  work  is  of  value.  All  of  us  are  breathing  in 
these  bacilli  every  day  of  our  lives,  but  many  of  us  escape  tubercu- 
losis because  the  opsonic  power  of  our  blood  is  sufficiently  high  to 
render  the  bacilli  an  easy  prey  to  leucocytes.  In  those  to  whom  the 
organism  is  pathogenic,  the  modern  treatment  is  directed  to  enhanc- 
ing nature's  cure  by  increasing  the  opsonic  power  of  the  patient's 
blood  by  good  food  and  pure  air,  or  the  injection  of  preparations  of 
the  required  opsonin. 

Lastly,  we  come  to  a  question  which  more  directly  appeals  to  the 
physiologist  than  the  preceding,  because  experiments  in  relation  to 
immunity  have  furnished  us  with  what  has  hitherto  been  lacking,  a 
means  of  distinguishing  human  blood  from  the  blood  of  other 
animals. 

The  discovery  was  made  by  Tchistovitch  (1899),  and  his  original 
experiment  was  as  follows: — Eabbits,  dogs,  goats,  and  guinea-pigs 
were  inoculated  with  eel-serum,  which  is  toxic :  he  thereby  obtained 
from  these  animals  an  antitoxic  serum.  But  the  serum  was  not  only 
antitoxic,  but  produced  a  precipitate  when  added  to  eel-serum,  but 
not  when  added  to  the  serum  of  any  other  animal.  In  other  words, 
not  only  has  a  specific  antitoxin  been  produced,  but  also  a  specific 
precipitin.  Numerous  observers  have  since  found  that  this  is  a 
general  rule  throughout  the  animal  kingdom,  including  man.  If,  for 
instance,  a  rabbit  is  treated  with  human  blood,  the  serum  ultimately 
obtained  from  the  rabbit  contains  a  specific  precipitin  for  human 
blood;  that  is  to  say,  a  precipitate  is  formed  on  adding  such  a 
rabbit's  serum  to  human  blood,  but  not  on  adding  it  to  the  blood  of 
any  other  animal.  There  may  be  a  slight  reaction  with  the  blood 
of  allied  animals ;  for  instance,  with  monkey's  blood  in  the  case  of 
man.  The  great  value  of  the  test  is  its  delicacy ;  it  will  detect  the 
specific  blood  when  it  is  greatly  diluted,  after  it  has  been  dried  for 
weeks,  or  even  when  it  is  mixed  with  the  blood  of  other  animals. 

The  lipoids  contained  in  cells  (mainly  in  the  cell-membrane)  play  some  part  in 
the  relationship  of  such  cells  to  toxins.  The  matter  has  been  mainly  studied  in 
relation  to  red  corpuscles,  and  the  hsemolysins  (such  as  snake-venom,  saponin,  etc.), 
which  attack  them.  There  is  some  evidence  that  the  cholesterin  in  the  envelope  of 
the  red  corpuscles  is  a  protective  agent  (see  also  p.  435).  A  few  years  ago,  Preston 
Kyes  stated  that  lecithin  is  the  amboceptor  which  anchors  the  hsemolysin  on  to 
the  red  cells.  But  more  recent  research  has  failed  to  substantiate  this  view,  and 
the  compounds  which  Kyes  described  and  called  lecithides  are  impure  mixtures 
of  several  substances.  It  is  much  more  probable  that  the  real  agent  at  work 
in  haemoylsis  is  a  lipolytic  or  fat-splitting  enzyme ;  this  splits  up  the  lecithin  of 
the  cell,  liberating  oleic  acid  and  deoleolecithin  (that  is,  lecithin  minus  its  oleic 
acid  radical),  and  it  is  these  cleavage  products  which  dissolve  out  the  haemoglobin 
and  so  destroy  the  corpuscles. 


478  THE  BLOOD  [CH.  XXIX. 

Anaphylaxis. — The  word  anaphylaxis  dates  'from  1905  and  was 
coined  by  Kichet ;  he  was  studying  the  action  of  poisons  obtained 
from  the  sea  anemone,  and  he  found  that  if  a  small  dose  which 
caused  no  symptoms  in  a  dog  was  followed  a  week  or  two  later  by 
the  same  small  dose,  the  animal  became  ill  and  usually  died.  This 
increased  susceptibility  lasted  a  considerable  time,  and  he  called  it 
anaphylaxis  (ana  against,  phylaxis  protection).  Since  this  time  it 
has  been  found  that  most  antigens  produce  a  similar  condition,  but 
the  phenomenon  was  really  known  before  Bichet  gave  it  its  name. 
For  instance,  in  vaccination  the  incubation  period  is  four  days ;  in  a 
second  vaccination  this  period  is  shortened,  and  the  increased  power 
of  the  body  to  respond  readily  is  in  this  case  not  harmful  but 
beneficial.  Similarly,  the  tuberculous  patient  is  hypersensitive  to 
tuberculin.  Anaphylaxis  has  been  largely  studied  in  the  guinea-pig, 
and  it  is  remarkable  how  small  is  the  dose  of  a  foreign  protein  which 
produces  the  exaggerated  sensitiveness.  A  millionth  part  of  a  cubic 
centimetre  of  bone  serum  is  often  enough.  Very  small  amounts  also 
will  produce  a  serious  condition  or  even  a  fatal  result  when  the  second 
dose  is  given.  In  face  of  such  small  figures  it  seems  hopeless  to 
isolate  the  toxic  principle.  The  hypersensitive  state  may  be  trans- 
mitted by  the  female  guinea-pig  to  her  offspring.  Death,  when  it 
occurs  as  the  result  of  a  second  dose,  is  usually  a  matter  of  minutes 
only ;  the  blood  pressure  falls  enormously,  the  abdominal  viscera  are 
gorged  with  blood,  and  haemorrhages  are  frequent;  the  bronchial 
muscles  are  also  acutely  constricted.  Numerous  theories  have 
been  advanced  to  explain  these  remarkable  facts,  and  numerous 
names,  such  as  anaphylactin,  sensibiline,  etc.,  have  been  invented 
for  the  supposed  toxic  material.  There  is  some  evidence  that  the 
precipitin  content  of  the  serum  runs  parallel  with  the  severity  of 
the  symptoms,  and  that  this  is  the  factor  to  which  the  difference 
between  the  normal  and  the  sensitive  animal  is  due.  But  how  the 
interaction  of  precipitin  and  antigen  produces  the  symptoms  is 
entirely  a  matter  of  speculation. 


CHAPTEE   XXX 

FOOD 

THE  chief  chemical  compounds  or  proximate  principles  in  food  aro : — 


1.  Proteins   . 

2.  Carbohydrates 

3.  Fats 

4.  Water       . 

5.  Salts 


organic. 


inorganic. 


In  milk  and  in  eggs,  which  form  the  exclusive  foods  of  young 
animals,  all  varieties  of  these  proximate  principles  are  present  in 
suitable  proportions.  Hence  they  are  spoken  of  as  perfect  foods. 
Eggs,  though  a  perfect  food  for  the  developing  bird,  contain  too  little 
carbohydrate  for  a  mammal.  In  most  vegetable  foods  carbohydrates 
are  in  excess ;  while  in  animal  foods,  such'as  meat,  the  proteins  are 
predominant.  In  a  suitable  diet  these  should  be  mixed  in  proper  pro- 
portions, which  must  vary  for  herbivorous  and  carnivorous  animals. 

A  healthy  and  suitable  diet  must  possess  the  following  char- 
acters : — 

1.  It   must  contain  the  proper  amount  and   proportion  of   the 
various  proximate  principles. 

2.  It  must  be  adapted  to  the  climate ;  to  the  age  and  weight  of 
the  individual,  and  to  the  amount  of  work  done  by  him. 

3.  The   food  must   contain   not   only  the  necessary  amount  of 
proximate  principles,  but  these  must  be  present  in  a  digestible  form. 
As  an  instance  of  this,  many  vegetables  (peas,  beans,  lentils)  contain 
even  more  protein  than  beef  or  mutton,  but  are  not  so  nutritious,  as 
they  are  less  digestible,  much  passing  off  in  the  faeces  unused. 

The  nutritive  value  of  a  diet  depends  chiefly  on  the  amount  of 
carbon  and  nitrogen  it  contains.  A  man  doing  a  moderate  amount  of 
work  and  taking  the  usual  diet  will  eliminate,  chiefly  from  the  lungs, 
in  the  form  of  carbonic  acid,  from  250  to  280  grammes  of  carbon  per 
diem.  During  the  same  time  he  will  eliminate,  chiefly  in  the  form 
of  urea  in  the  urine,  about  15  to  18  grammes  of  nitrogen.  These 
substances  are  derived  partly  from  the  food  and  partly  from  the 
metabolism  of  the  tissues,  various  forms  of  energy — mechanical  motion 

479 


480  FOOD  [CH.  XXX. 

and  heat  being  the  chief — being  simultaneously  liberated.  During 
muscular  exercise  the  output  of  carbon  greatly  increases ;  the  increased 
excretion  of  nitrogen  is  not  noticeable.  Taking,  then,  the  state  of 
moderate  exercise,  it  is  necessary  that  the  waste  should  be  replaced 
by  fresh  material  in  the  form  of  food ;  and  the  proportion  of  carbon 
to  nitrogen  should  be  the  same  as  in  the  excretions :  250  to  15,  or 
16 '6  to  1.  The  proportion  of  carbon  to  nitrogen  in  protein  is,  how- 
ever, 53  to  15,  or  3 "5  to  1.  The  extra  supply  of  carbon  must  come 
from  non-nitrogenous  food — viz.,  fat  and  carbohydrate. 
Voit  gives  the  following  daily  diet : — 

Protein 120  grras. 

Fat 100     „ 

Carbohydrate 333     „ 

Kanke's  diet  closely  resembles  Voit's ;  it  is  — 

Protein 100  grms. 

Fat .         .         .     100     „ 

Carbohydrate 250     „ 

Such  typical  diets  as  these  must  not  be  considered  as  more  than 
rough  averages  of  what  is  necessary  for  a  man  in  the  course  of  the 
day.  Actual  experience  shows  that  in  the  diets  of  different  nations 
there  are  considerable  variations  from  this  standard  without  the 
production  of  ill  effects.  Age,  and  the  amount  of  work  done,  also 
influence  the  amount  of  food  necessary ;  growing  children,  for  instance, 
require  a  relatively  rich  diet ;  thus,  milk,  the  diet  of  the  infant,  is 
proportionally  twice  as  rich  in  proteins,  and  half  as  rich  again  in 
fats,  as  the  normal  diet  given  above.  During  work  more  food  is 
necessary  than  during  inactivity. 

Attention  has  recently  been  devoted  to  the  question  whether  as 
much  protein  as  100  to  120  grammes  daily  is  really  necessary,  and 
by  far  the  most  convincing  of  the  experiments  published  in  favour 
of  a  reduction  are  those  carried  out  by  Chittenden  en  himself,  his 
colleagues,  his  students,  and  on  soldiers  and  athletes,  over  compara- 
tively long  periods  of  time.  The  protein  intake  was  reduced  to  half 
and  sometimes  to  less  than  half  the  quantity  hitherto  regarded  as 
necessary.  The  deprivation  was  followed  by  no  untoward  results ; 
bodily  equilibrium  was  maintained ;  the  health  remained  perfect  or 
improved;  the  muscular  force  in  athletes  was  increased;  mental 
acuity  was  undiminished,  and  desire  for  richer  food  soon  disappeared. 

It  may  be  freely  admitted  that  the  majority  of  well-to-do  people 
eat  too  much  protein;  there  are  not  many  who  limit  themselves 
even  to  Voit's  minimum,  and  in  those  who  are  prone  to  digestive  and 
uric  acid  diseases,  one  cannot  but  feel  that  improvement  in  body  and 
mind  would  be  the  result  of  more  temperate  habits. 

But  if  we  were  all  to  permanently  reduce  our  diet  to  the 
Chittenden  level,  we  might  be  living  perilously  near  the  margin; 


CH.  XXX.]  MILK  481 

any  unusual  strain,  such  as  privation  or  a  severe  illness,  would  then 
find  us  without  any  reserve  of  nutrient  energy,  and  we  should 
probably  suffer  more  severely  in  consequence.  The  poor  around  us 
have  had  nolens  volens  to  subsist  on  a  Chittenden  diet  for  years, 
whereas  Chittenden's  experiments  only  lasted  months,  and  nearly  all 
of  his  subjects  have  returned  now  to  their  previous  diet.  The 
underfed  condition  of  the  poor  is  apparent,  and  is  not  such  as  to 
make  others  inclined  to  follow  their  example.  In  countries  like 
India,  where  the  vegetarian  native  population  is  diluted  with  the 
meat-eating  white  races,  it  is  the  former  who  more  readily  succumb 
to  the  effects  of  disease.  The  recent  development  of  the  Japanese 
is  by  some  attributed  in  part  to  the  fact  that  they  are  accustoming 
themselves  to  a  richer  nitrogenous  diet  than  they  took  in  the  past. 

It  is  doubtful  if  the  minimum  is  also  the  optimum.  We  take  in 
protein,  and  rapidly  eliminate  most  of  its  nitrogen  as  urea,  without 
building  it  up  first  into  the  body  tissues ;  but  some  is  wanted  by  the 
body  tissues  to  repair  their  waste,  and  some  of  the  cleavage  products 
of  the  food-protein  are  especially  necessary  for  the  synthesis  of  tissue 
protein ;  it  is  in  order  to  obtain  a  sufficient  quantity  of  these 
scanty  cleavage  products  that  we  ingest  what  at  first  sight  is  an 
excess  of  the  proteins  which  yield  them.  But  after  our  study  of 
digestion  and  excretion,  we  shall  be  in  a  better  position  to  discuss 
this  question  more  fully,  and  we  shall  return  to  it  in  the  chapter 
on  Metabolism. 

Milk. 

Milk,  which  we  have  already  spoken  of  as  a  perfect  food,  is  only 
so  for  young  children.  For  those  who  are  older,  it  is  so  voluminous 

that  unpleasantly  large  quantities  of 
it  would  have  to  be  taken  in  the 
course  of  the  day  to  ensure  the  proper 
supply  of  nitrogen  and  carbon.  More- 
over, it  is  relatively  too  rich  in  protein 
and  fat.  It  also  contains  too  little 
iron  (Bunge):  hence  children  weaned 
late  become  anaemic. 

The  microscope  reveals  that  it  con- 
sists of  two  parts :  a  clear  fluid  and  a 
number  of  minute  particles  that  float 
in  it.  These  consist  of  minute  oil 
globules,  varying  in  diameter  from 
FIG.  ass.— Globules  of  cow's  milk,  x  400.  0'0015  to  0*005  millimetre  (fig.  338). 

The  milk  secreted  during  the  first 

few  days  of  lactation  is  called  colostrum.  It  contains  very  little 
caseinogen,  but  large  quantities  of  albumin  and  globulin  instead.  It 

2  11 


482 


FOOD 


[CH.  XXX. 


coagulates-  like  white  of  egg  when  boiled.  Microscopically,  cells 
from  the  acini  of  the  mammary  gland  are  seen,  which  contain  fat 
globules  in  their  interior ;  they  are  called  colostrum  corpuscles. 

Reaction  and  Specific  Gravity. — The  reaction  of  fresh  cow's 
milk  and  of  human  milk  is  amphoteric ;  that  is,  it  turns  blue  litmus 
red,  and  red  litmus  blue.  This  is  due  to  the  presence  of  both  acid  and 
alkaline  salts.  All  milk  readily  turns  acid  or  sour  as  the  result  of 
fermentative  change,  part  of  its  lactose  being  transformed  into  lactic 
acid.  The  specific  gravity  of  milk  is  usually  ascertained  with  the 
hydrometer.  That  of  normal  cow's  milk  varies  from  1028  to  1034. 
When  the  milk  is  skimmed  the  specific  gravity  rises,  owing  to  the 
removal  of  the  light  constituent,  the  fat,  to  1033  to  1037.  In  all 
cases  the  specific  gravity  of  water,  with  which  other  substances  are 
compared,  is  taken  as  1000. 

Composition. — Bunge  gives  the  following  table,  contrasting  the 
milk  of  woman,  and  the  cow : — 


Woman. 

Cow. 

Per  cent. 

Per  cent. 

Proteins  (chiefly  caseinogen)       .             1  '7 
Butter  (fat)  3  -4 

3-5 
3-7 

Lactose        6  "2 

4-9 

Salts    

0-2 

07 

Hence,  in  feeding  infants  on  cow's  milk,  it  is  necessary  to  dilute  it, 
and  add  sugar  and  a  little  cream  to  make  it  approximately  equal  to 
natural  human  milk. 

The  Proteins  of  Milk. — The  principal  protein  in  milk  is  called 
caseinogen  ;  it  is  precipitable  by  acids  such  as  acetic  acid,  and  also  by 
saturation  with  magnesium  sulphate,  or  half  saturation  with  ammonium 
sulphate,  so  resembling  globulins ;  it  is  coagulated  by  rennet  to  form 
casein.  Cheese  consists  of  casein  with  the  entangled  fat.  The  other 
protein  in  milk  is  an  albumin.  It  is  present  in  small  quantities  only ; 
it  differs  in  some  of  its  properties  (specific  rotation,  coagulation 
temperature,  etc.)  from  serum-albumin ;  it  is  called  lact-albumin. 

The  Coagulation  of  Milk. — Kennet  is  the  agent  usually  employed 
for  this  purpose :  it  is  a  enzyme  secreted  by  the  stomach,  especially 
in  sucking  animals,  and  is  generally  obtained  from  the  calf. 

The  curd  consists  of  the  casein  and  entangled  fat:  the  liquid 
residue  called  whey  contains  the  sugar,  salts,  and  albumin  of  the  milk. 
There  is  also  a  small  quantity  of  a  new  protein  called  whey -protein, 
which  differs  from  caseinogen  by  not  being  convertible  into  casein ; 
this  is  produced  by  the  decomposition  of  the  caseinogen  molecule 
during  the  process  of  curdling. 


CH.  XXX.]  VARIETIES   OF   MILK  483 

The  addition  of  rennet  produces  coagulation  in  milk,  provided 
that  a  sufficient  amount  of  calcium  salts  is  present.  If  the  calcium 
salts  are  precipitated  by  the  addition  of  potassium  oxalate,  rennet 
causes  no  formation  of  casein.  The  process  of  curdling  in  milk  is  a 
double  one ;  the  first  action  due  to  rennet  is  to  produce  a  change  in 
caseinogen ;  the  second  action  is  that  of  the  calcium  salt,  which 
precipitates  the  altered  caseinogen  as  casein.  In  blood,  also,  calcium 
salts  are  necessary  for  coagulation,  but  there  they  act  in  a  different 
way,  namely,  in  the  production  of  fibrin-ferment  (see  p.  449). 

Caseinogen  is  a  phospho-protein  (see  p.  429).  In  milk  it  is  com- 
bined with  calcium  to  form  calcium  caseinogenate ;  when  acetic  acid 
is  added,  we  therefore  get  calcium  acetate  and  free  caseinogen. 

The  Pats  of  Milk. — The  chemical  composition  of  the  fat  of  milk 
(butter)  is  very  like  that  of  adipose  tissue.  There  are,  however, 
smaller  quantities  of  fats  derived  from  fatty  acids  lower  in  the 
series,  especially  butyrin  and  caproin.  The  relation  between  these 
varies  somewhat,  but  the  proportion  is  roughly  as  follows: — Olein, 
f ;  palmitin,  J  ;  stearin,  J ;  butyrin,  caproin,  and  caprylin,  yT.  The 
old  statement  that  each  fat  globule  is  surrounded  by  a  film  of 
protein  is,  according  to  Kamsden's  recent  observations,  correct. 
Milk  also  contains  small  quantities  of  lipoids  (lecithin,  cholesterin, 
and  a  yellow  fatty  pigment  or  lipochrome). 

Milk  Sugar,  or  Lactose. — This  is  a  disaccharide  (C12H22On).  Its 
properties  have  already  been  described  in  Chap.  XXYI1L,  p.  411. 

Souring  of  Milk. — When  milk  is  allowed  to  stand,  the  chief 
change  which  it  is  apt  to  undergo  is  a  conversion  of  a  part  of  its 
lactose  into  lactic  acid.  This  is  due  to  the  action  of  an  enzyme 
secreted  by  micro-organisms,  and  would  not  occur  if  the  milk  were 
contained  in  closed  sterilised  vessels.  Equations  showing  the  change 
produced  are  given  on  p.  411.  When  souring  occurs,  the  acid  formed 
precipitates  a  portion  of  the  caseinogen.  This  must  not  be  con- 
founded with  the  formation  of  casein  from  caseinogen,  which  is 
produced  by  rennet.  There  are,  however,  some  bacteria  which,  like 
rennet,  produce  true  coagulation. 

Alcoholic  Fermentation  of  Milk. — When  yeast  is  added  to  milk, 
the  sugar  does  not  readily  undergo  the  alcoholic  fermentation.  Other 
somewhat  similar  fungoid  growths  are,  however,  able  to  produce  the 
change,  as  in  the  preparation  of  koumiss ;  the  milk  sugar  is  first 
inverted,  that  is,  dextrose  and  galactose  are  formed  from  it  (see  p.  411), 
and  it  is  these  sugars  from  which  alcohol  and  carbonic  acid  originate. 

The  Salts  of  Milk. — The  principal  salt  present  is  calcium  phos- 
phate; a  small  quantity  of  magnesium  phosphate  is  also  present. 
The  other  salts  are  chiefly  chlorides  of  sodium  and  potassium. 

It  is  an  undoubted  fact  that  the  milk  provided  by  Nature  for  the 
growing  offspring  is  different  in  the  various  classes  of  the  animal 


484  FOOD  [CH.  XXX. 

kingdom.  The  quantitative  variations  are  often  enormous,  and  it 
has  been  shown  that  the  milk  best  adapted  for  the  nutrition  of  the 
young  animal  is  that  which  comes  from  its  mother,  or,  at  least,  from 
an  animal  of  the  same  species.  The  practical  application  of  this 
rule  comes  home  most  to  us  when  dealing  with  the  feeding  of  children, 
and  it  is  universally  acknowledged  that,  after  all,  cows'  milk  is  but 
a  poor  substitute  for  human  milk.  Cows'  milk  is,  of  course,  diluted, 
and  sugar  and  cream  added,  so  as  to  make  it  quantitatively  like 
mothers'  milk,  but  even  then  the  question  arises  whether  the 
essential  difference  between  the  two  kinds  of  milk  is  not  deeper  than 
one  of  mere  quantity;  and,  in  particular,  the  pendulum  of  scientific 
opinion  has  swung  backwards  and  forwards  in  relation  to  the 
question  whether  the  principal  protein,  called  caseinogen,  in  both  is 
really  identical  in  the  two  cases.  The  caseinogen  of  human  milk 
curdles  in  small  flocculi  in  the  stomach,  so  contrasting  with  the 
heavy  curd  which  cows'  milk  forms;  and  even  although  the  curdling 
of  cows'  milk  be  made  to  occur  in  smaller  fragments  by  mixing  the 
milk  with  barley  water  or  lime  water,  its  digestion  proceeds  with 
comparative  slowness  in  the  child's  alimentary  canal.  These  are 
practical  points  well  known  to  every  clinical  observer,  and  in  the 
past  they  have  been  attributed,  not  so  much  to  fundamental 
differences  in  the  caseinogen  itself,  as  to  accidental  concomitant 
factors ;  the  excess  of  citric  acid  in  human  milk,  for  instance,  and  its 
paucity  in  calcium  salts,  have  been  held  responsible  for  the 
differences  observed  in  the  physical  condition  of  the  curd  and  in  its 
digestibility. 

This  question  is  far  from  settled  even  to-day,  but  there  are  some 
data  now  available  that  point  to  a  qualitative  difference  between 
caseinogens.  Some  of  these  depend  on  the  application  of  the 
"  biological  test "  carried  out  on  the  line  of  immunity  experiments, 
which  has  been  so  signally  successful  in  the  distinction  between  the 
blood-proteins  of  different  species  of  animals  (see  p.  477).  The 
differences,  however,  which  lead  to  the  formation  of  specific  pre- 
cipitins  are  so  slight,  that  ordinary  chemical  methods  of  analysis  are, 
at  present,  unable  to  reveal  them.  But,  in  the  case  of  milk,  there 
are  differences  which  the  chemist  can  detect.  One  cannot  lay  much 
stress  on  mere  percentage  composition,  although  differences  have 
been  noted  in  that,  because  we  have  no  guarantee  that  the  proteins 
investigated  were  separated  from  all  impurities ;  there  are  also  small 
differences  in  the  percentage  of  mono-amino-acids  obtained  after 
hydrolysis ;  but  the  present  methods  of  estimating  these  with 
accuracy  leave  much  to  be  desired.  A  deeper  chemical  distinction 
noted  is  contained  in  the  recent  work  of  Bienenfeld,  who  finds  that 
human  caseinogen  contains  a  carbohydrate  complex  which  is  absent 
from  that  of  the  cow. 


CH.  XXX.] 


THE   MAMMAKY   GLANDS 


485 


A  few  years  ago  it  was  stated  that  human  casein ogen  will  not 
curdle  with  rennet ;  but  this  ha^  been  shown  to  be  a  mistake.  The 
conditions  of  rennet  curdling  are  somewhat  different  in  the  two  kinds 
of  milk  we  are  considering,  but  provided  the  reaction  in  the  stomach 
is  acid,  human  milk  is  curdled  by  rennet  when  acted  on  by  gastric 
juice. 

The  Mammary  Glands. 

The  mammary  glands  are  composed  of  large  divisions  or  lobes,  and  these  are 
again  divisible  into  lobules  ;  the  lobules  are  composed  of  the  convoluted  and  dilated 
subdivisions  of  the  main  ducts  held  together  by  connective  tissue.  Covering  the 
general  surface  of  the  gland,  with  the  exception  of  the  nipple,  is  a  considerable 
quantity  of  fat,  itself  lobulated  by  sheaths  and  processes  of  areolar  tissue  (fig.  339) 


I 


FIG.  339. — Dissection  of  the  lower  half  of  the  female  mamma,  during  the  period  of  lactation.  <j. — In  the 
left-hand  side  of  the  dissected  part  the  glandular  lobes  are  exposed  and  partially  unravelled ;  and 
on  the  right-hand  side,  the  glandular  substance  has  been  removed  to  show  the  reticular  loculi  of 
the  connective  tissue  in  which  the  glandular  lobules  are  placed  :  1,  upper  part  of  the  mamilla  or 
nipple  ;  2,  areola ;  3,  subcutaneous  masses  of  fat ;  4,  reticular  loculi  of  the  connective  tissue  which 
support  the  glandular  substance  and  contain  the  fatty  masses ;  5,  one  of  three  lactiferous  ducts 
shown  passing  towards  the  nipple  where  they  open ;  6,  one  of  the  sinus  lactei  or  reservoirs ;  7, 
some  of  the  glandular  lobules  which  have  been  unravelled  ;  7',  others  massed  together.  (Luschka.) 

connected  both  with  the  skin  in  front  and  the  gland  behind;  the  same  bond  of 
connection  extends  also  from  the  under  surface  of  the  gland  to  the  sheathing 
connective  tissue  of  the  great  pectoral  muscle  on  which  it  lies.  The  main  ducts  of 
the  gland,  fifteen  to  twenty  in  number,  called  the  lactiferous  ducts,  are  formed  by 
the  union  of  the  smaller  (lobular)  ducts,  and  open  by  small  separate  orifices  through 
the  nipple.  At  the  points  of  junction  of  lobular  ducts  to  form  lactiferous  ducts,  and 
just  before  these  enter  the  base  of  the  nipple,  the  ducts  are  dilated ;  and  during  the 
period  of  active  secretion  by  the  gland,  the  dilatations  form  reservoirs  for  the  milk, 
which  collects  in  and  distends  them.  The  walls  of  the  gland-ducts  are  formed  of  areolar 
frith  some  unstriped  muscular  tissue,  and  are  lined  internally  by  short  columnar  and 
near  the  nipple  by  flattened  epithelium. 


486 


FOOD 


[CH.  XXX. 


The  nipple  is  composed  of  areolar  tissue,  and  contains  unstriped  muscular  fibres. 
Blood-vessels  are  also  freely  supplied  to  it,  so  as  to  give  it  an  erectile  structure.  On 
its  surface  are  very  sensitive  papillae ;  and  around  it  is  a  small  area  or  areola  of 
pink  or  dark-tinted  skin,  on  which  are  to  be  seen  small  projections  formed  by 
minute  secreting  glands. 

Blood-vessels,  nerves,  and  lymphatics  are  plentifully  supplied  to  the  mammary 
glands ;  the  calibre  of  the  blood-vessels,  as  well  as  the  size  of  the  glands,  varies 
very  greatly  under  certain  conditions,  especially  those  of  pregnancy  and  lactation. 

The  alveoli  of  the  glands  during  the  secreting  periods  are  found  to  be  lined 
with  short  columnar  cells  (see  fig.  340).  The  edges  of  the  cells  towards  the  lumen 
may  be  irregular  and  jagged,  and  the  remainder  of  the  alveolus  is  filled  up  with  the 
materials  of  the  milk.  During  the  intervals  between  the  acts  of  discharge,  the 
cells  of  the  alveoli  elongate  towards  the  lumen,  their  nuclei  divide,  and  in  the 
part  of  the  cells  towards  the  lumen  a  collection  of  oil  globules  and  of  other 
materials  takes  place. 

The  next  stage  is  that  the  cells  divide  and  the  part  of  each  towards  the  lumen 
containing  a  nucleus  and  the  materials  of  the  secretion,  disintegrates  and  goes  to 
form  the  constituents  of  the  milk. 

In  the  earlier  days  of  lactation,  epithelial 
cells  only  partially  transformed  are  discharged  in 
the  secretion ;  these  are  termed  colostrum  cor- 


During  pregnancy  the  mammary  glands 
undergo  changes  (evolution)  which  are  readily 
observable.  They  enlarge,  become  harder,  and 
more  distinctly  lobulated ;  the  veins  on  the  sur- 
face become  more  prominent.  The  areola  becomes 
enlarged  and  dusky,  with  projecting  papillae;  the 
nipple,  too,  becomes  more  prominent,  and  milk  can 
be  squeezed  from  the  orifices  of  the  ducts.  This  is 
a  very  gradual  process,  which  commences  about 
the  time  of  conception,  and  progresses  steadily 
during  the  whole  period  of  gestation.  In  the 
gland  itself  solid  columns  of  cells  bud  off  from 
the  old  alveoli  to  form  new  alveoli.  But  these 
solid  columns  after  a  while  are  converted  into 
tubes  by  the  central  cells  becoming  fatty  and  being 
discharged  as  the  colostrum  corpuscles  above 
mentioned.  After  the  end  of  lactation,  the  mamma 

gradually  returns  to  its  original  size  (involution).  The  acini,  in  the  early  stages  of 
involution,  are  lined  with  cells  in  all  degrees  of  vacuolation.  As  involution  pro- 
ceeds, the  acini  diminish  considerably  in  size,  and  at  length,  instead  of  a  mosaic  of 
lining  epithelial  cells  (twenty  to  thirty  in  each  acinus),  we  have  five  or  six  nuclei 
(some  with  no  surrounding  protoplasm)  lying  in  an  irregular  heap  within  the  acinus. 
No  secretory  nerves  of  the  mammary  gland  have  yet  been  discovered.  It  is 
possible  they  do  not  exist,  but  the  normal  stimulus  to  mammary  activity  is  a 
chemical  one  formed  by  the  ovary. 


FIG.  340. — Section  of  mammary  gland 
of  bitch,  showing  acini,  lined 
with  epithelial  cells  of  a  short 
columnar  form,  x  200.  (V.  D. 
Harris.) 


Eggs. 

In  this  country  the  eggs  of  hens  and  ducks  are  those  particularly 
selected  as  foods.  The  chief  constituent  of  the  shell  is  calcium  car- 
bonate. The  white  is  composed  of  a  richly  albuminous  fluid  enclosed 
in  a  network  of  firmer  and  more  fibrous  material.  The  amount  of 
solids  is  13*3  per  cent. ;  of  this,  12 '2  is  protein  in  nature  (egg-albumin, 
with  smaller  quantities  of  egg-globulin,  and  of  a  mucinoid  substance 
called  ovo-mucoid),  and  the  remainder  is  made  up  of  sugar  (0'5  per 


CH.  XXX.] 


MEAT 


487 


cent.),  traces  of  fats,  lecithin,  and  cholesterin,  and  0'6  per  cent,  of 
inorganic  salts.  The  yolk  is  rich  in  food  materials  for  the  develop- 
ment of  the  future  embryo.  In  it  there  are  two  varieties  of  yolk- 
spherules,  one  kind  yellow  and  opaque  (due  to  admixture  with  fat 
and  a  yellow  lipochrome),  and  the  other  smaller,  transparent,  and 
almost  colourless;  these  are  protein  in  nature,  consisting  of  the 
phospho-protein  called  vitellin.  Small  quantities  of  sugar,  lecithin, 
cholesterin,  and  inorganic  salts  are  also  present. 

The  nutritive  value  of  eggs  is  high,  as  they  are  so  readily  digest- 
ible ;  but  the  more  an  egg  is  cooked  the  more  insoluble  do  its  protein 
constituents  become. 

Meat. 

This  is  composed  of  the  muscular  and  connective  (including  adipose) 
tissues  of  certain  animals.  The  flesh  of  some  animals  is  not  eaten ; 
in  some  cases  this  is  a  matter  of  fashion,  in  others,  it  is  due  to  an 
unpleasant  taste,  such  as  the  flesh  of  carnivora  is  said  to  have ;  and 
in  other  cases  (e.g.  the  horse)  because  it  is  more  lucrative  to  use  the 
animal  as  a  beast  of  burden. 

Meat  is  the  most  concentrated  and  most  easily  assimilable  of 
nitrogenous  foods.  It  is  our  chief  source  of  nitrogen.  Its  chief  solid 
constituent  is  protein,  and  the  principal  protein  is  myosin.  In  addition 
to  the  extractives  and  salts  contained  in  muscle,  there  is  always  a 
certain  percentage  of  fat,  even  though  all  visible  adipose  tissue  is 
dissected  off.  The  fat-cells  are  placed  between  the  muscular  fibres, 
and  the  amount  of  fat  so  situated  varies  in  different  animals ;  it  is 
particularly  abundant  in  pork ;  hence  the  indigestibility  of  this  form 
of  flesh :  the  fat  prevents  the  gastric  juice  from  obtaining  ready  access 
to  the  muscular  fibres. 

The  following  table  gives  the  chief  substances  in  some  of  the 
principal  meats  used  as  food : — 


Constituents. 

Ox. 

Calf. 

Pig. 

Horse. 

Fowl. 

Pike. 

Water  . 

76-7 

75-6 

72-6      74-3 

70-8      79-3 

Solids  . 

, 

.         . 

23-3 

24-4      27'4 

257 

29-2      20-7 

Proteins 

,  including  gelatin 

20-0 

19-4      19-9 

21-6 

22-7      18-3 

Fat       . 

. 

1-5 

2-9        6-2 

2-5 

4-1 

0'7 

Carbohydrate 

0-6 

0-8        0-6 

0-6 

1-3 

0'9 

Salts     . 

• 

• 

1-2 

1-3        1-1 

1-0 

1-1 

0-8 

*  The  flesh  of  young  animals  is  richer  in  gelatin  than  that  of  old ;  thus  1000 
parts  of  beef  yield  6,  of  veal  50,  parts  of  gelatin. 

The  large  percentage  of  water  in  meat  should   be   particularly 
noted ;  if  a  man  wished  to  take  his  daily  supply  of  100  grammes  of 


488  FOOD  [CH.  XXX. 

protein  entirely  in  the  form  of  meat,  it  would  be  necessary  for  him 
to  consume  about  500  grammes  (i.e.  a  little  more  than  1  Ib.)  of  meat. 

Flour. 

The  best  wheat  flour  is  made  from  the  interior  of  wheat  grains, 
and  contains  the  greater  proportion  of  the  starch  of  the  grain  and 
most  of  the  protein.  Whole  flour  is  made  from  the  whole  grain 
minus  the  husk,  and  thus  contains  not  only  the  white  interior  but 
also  the  harder  and  browner  outer  portion  of  the  grain  and  the 
germ  or  embryo  plant.  This  region  contains  a  somewhat  larger  pro- 
portion of  protein.  Whole  flour  contains  1  to  2  per  cent,  more 
protein  than  the  best  white  flour,  but  it  has  the  disadvantage  of 
being  less  readily  digested.  Brown  flour  contains  a  certain  amount 
of  bran  in  addition ;  it  is  still  less  digestible,  but  is  useful  as  a  mild 
laxative,  the  insoluble  cellulose  mechanically  irritating  the  intestinal 
canal  as  it  passes  along. 

The  best  flour  contains  very  little  sugar.  The  presence  of  sugar 
indicates  that  germination  has  commenced  in  the  grains.  In  the 
manufacture  of  malt  from  barley  this  is  purposely  allowed  to  go  on. 

When  mixed  with  water,  wheat  flour  forms  a  sticky,  adhesive  mass 
called  dough.  This  is  due  to  the  formation  of  gluten.  Gluten  is  a 
mixture  of  two  proteins — namely,  gliadin,  which  is  soluble  in  alcohol, 
and  glutenin,  which  is  soluble  in  alkali  (see  p.  433).  The  adhesive 
character  of  gluten  is  due  to  gliadin  ;  grains  which  are  poor  in  gliadin 
(e.g.  rice)  cannot  be  used  for  bread-making. 

The  following  table  contrasts  the  composition  of  some  of  the  more 
important  vegetable  foods : — 


Constituents. 

Wheat. 

Barley. 

Oats.           Rice. 

Lentils.        Peas. 

Potatoes. 

Water. 

13-6 

13'8 

12-4           13-1 

12-5          14-8 

76-0 

Protein 

12-4 

11*1 

10*4             7'9 

24-8          237 

2-0 

Fat      . 

1-4 

2-2 

5'2            0-9 

1-9            1-6 

0-2 

Starch 

67-9 

64-9 

57-8         76-5 

54-8          49-3 

20-6 

Cellulose 

2-5 

5-3 

11-2     ,       0-6 

3-6           7-5 

0-7 

Mineral  salts 

1-8 

2-7 

3-0           1-0 

2-4            3-1 

1-0 

We  see  from  this  table— 

1.  The  great  quantity  of  starch  always  present. 

2.  The  small  quantity  of  fat ;  that  bread  is  generally  eaten  with 
butter  is  a  popular  recognition  of  this  fact. 

3.  Protein,  except  in  potatoes,  is  pretty  abundant,  and  especially 
so  in  the  pulses  (lentils,  peas,  etc.).     The  protein  in  the  pulses  is  not 
gluten,  but  consists  mainly  of  globulins. 

In  the  mineral  matters  in  vegetables,  salts  of  potassium  and  mag- 
nesium are,  as  a  rule,  more  abundant  than  those  of  sodium  and  calcium. 


CH.  XXX.]  BKEAD  489 

Bread. 

Bread  is  made  by  cooking  the  dough  of  wheat  flour  mixed  with 
yeast,  salt,  and  flavouring  materials.  An  enzyme  in  the  flour  acts  at 
the  commencement  of  the  process,  when  the  temperature  is  kept  a 
little  over  that  of  the  body,  and  forms  dextrin  and  sugar  from  the 
starch,  and  then  the  alcoholic  fermentation,  due  to  the  action  of  the 
yeast,  begins.  The  bubbles  of  carbonic  acid,  burrowing  passages 
through  the  bread,  make  it  light  and  spongy.  This  enables  the 
digestive  juices  subsequently  to  soak  into  it  readily  and  affect  all 
parts  of  it.  In  the  later  stages,  viz.,  baking,  the  temperature  is  raised, 
the  gas  and  alcohol  are  expelled  from  the  bread,  the  yeast  is  killed, 
and  a  crust  forms  from  the  drying  of  the  outer  portions  of  the  dough. 

White  bread  contains,  in  100  parts,  8  to  10  of  protein,  55  of 
carbohydrates,  1  of  fat,  2  of  salts,  and  the  rest  water. 

Cooking  of  Pood. 

The  cooking  of  foods  is  a  development  of  civilisation,  and  serves 
many  useful  ends : — 

1.  It  destroys  all  parasites  and  danger  of  infection.     This  relates 
not   only  to  bacterial  growths,  but  also  to  larger  parasites,  such  as 
tapeworms  and  trichinae. 

2.  In  the  case  of  vegetable  foods  it  breaks  up  the  starch  grains, 
bursting  the  cellulose  and  allowing  the  digestive  juices  to  «ome  into 
contact  with  the  granulose. 

3.  In  the  case  of  animal  foods  it  converts  the  insoluble  collagen  of 
the  universally  distributed  connective  tissues  into  the  soluble  gelatin. 
The  loosening  of  the  fibres  is  assisted  by  the  formation  of  steam 
between  them.     By  thus  loosening  the  binding  material,  the  more 
important  elements  of  the  food,  such  as  muscular  fibres,  are  rendered 
accessible  to  the  gastric  and  other  juices.     Meat  before  it  is  cooked  is 
generally  kept  a  certain  length  of  time  to  allow  rigor  mortis  to  pass  off. 

Of  the  two  chief  methods  of  cooking,  roasting  and  boiling,  the 
former  is  the  more  economical,  as  by  its  means  the  meat  is  first  sur- 
rounded with  a  coat  .of  coagulated  protein  on  its  exterior,  which  keeps 
in  the  juices  to  a  great  extent,  letting  little  else  escape  but  the  drip- 
ping (fat).  Whereas  in  boiling,  unless  both  bouillon  and  bouilli  are  used, 
there  is  considerable  waste.  Cooking,  especially  boiling,  renders  the 
proteins  more  insoluble  than  they  are  in  the  raw  state ;  but  this  is 
counterbalanced  by  the  other  advantages  that  cooking  possesses. 

In  making  beef  tea  and  similar  extracts  of  meat  it  is  necessary 
that  the  meat  should  be  placed  in  cold  water,  and  this  is  gradually 
and  carefully  warmed.  In  boiling  a  joint  it  is  usual  to  put  the  meat 
into  boiling  water  at  once,  so  that  the  outer  part  is  coagulated,  and 
the  loss  of  material  minimised. 


490  FOOD  [CTI.  xxx. 

An  extremely  important  point  in  this  connection  is  that  beef  tea 
and  similar  meat  extracts  should  not  be  regarded  as  foods.  They  are 
valuable  as  pleasant  stimulating  drinks  for  invalids,  but  they  contain 
very  little  of  the  nutritive  material  of  the  meat,  their  chief  con- 
stituents, next  to  water,  being  the  salts  and  extractives  of  flesh. 

Soup  contains  the  extractives  of  meat,  a  very  small  proportion  of 
the  myosin,  and  the  principal  part  of  the  gelatin.  The  gelatin  is 
usually  increased  by  adding  bones  and  fibrous  tissue  to  the  stock.  It 
is  the  presence  of  this  substance  which  causes  soup  when  cold  to 
gelatinise. 

Accessories  to  Pood. 

Among  these  must  be  placed  alcohol,  the  value  of  which  within 
moderate  limits  is  not  as  a  food  but  as  a  stimulant;  condiments 
(mustard,  pepper,  ginger,  curry  powder,  etc.),  which  are  stomachic 
stimulants,  the  abuse  of  which  is  followed  by  dyspeptic  troubles; 
and  tea,  coffee,  cocoa,  and  similar  drinks.  These  are  stimulants 
chiefly  to  the  nervous  system ;  tea,  coffee,  mate  (Paraguay),  guarana 
(Brazil),  cola  nut  (Central  Africa),  bush  tea  (South  Africa),  and 
a  few  other  plants  used  in  various  countries  all  owe  their  chief 
property  to  an  alkaloid  called  theine  or  caffeine  (C8H10N402) ;  cocoa  to 
the  closely  related  alkaloid,  theolromine  (C7H8N402) ;  coca  to  cocaine. 
These  alkaloids  are  all  poisonous,  and  used  in  excess,  even  in  the  form 
of  infusions  of  tea  and  coffee,  produce  over-excitement,  loss  of  diges- 
tive power,  and  other  disorders  well  known  to  physicians.  Coffee 
differs  from  tea  in  being  rich  in  aromatic  matters ;  tea  contains  a 
bitter  principle,  tannin ;  to  avoid  the  injurious  solution  of  too  much 
tannin,  tea  should  only  be  allowed  to  infuse  (draw)  for  a  few  minutes. 
Cocoa  is  not  only  a  stimulant,  but  a  food  in  addition ;  it  contains 
about  50  per  cent,  of  fat,  and  12  per  cent,  of  protein.  In  manufac- 
tured cocoa,  the  amount  of  fat  is  reduced  to  30  per  cent.,  and  the 
amount  of  protein  rises  proportionately  to  about  20  per  cent.  The 
quantity  of  cocoa  usually  consumed  is  too  small  for  these  food 
materials  to  count  very  much  in  the  daily  supply.  The  amount  of 
protein  in  solution  (mainly  proteose)  in  a  breakfast  cup  of  cocoa  is 
under  half  a  gramme ;  most  of  the  food  stuffs  are  in  suspension,  for 
cocoa  is  drunk  "thick,"  not  as  a  clear  infusion. 

Green  vegetables  are  taken  as  a  palatable  adjunct  to  other  foods, 
rather  than  for  their  nutritive  properties.  Their  potassium  salts  are, 
however,  abundant.  Cabbage,  turnips,  and  asparagus  contain  80  to 
92  water,  1  to  2  protein,  2  to  4  carbohydrates,  and  1  to  1/5  cellulose 
per  cent.  The  small  amount  of  nutriment  in  most  green  foods 
accounts  for  the  large  meals  made  by,  and  the  vast  capacity  of  the 
alimentary  canal  of,  herbivorous  animals. 


CH.  XXX.]      UNKNOWN   BUT   ESSENTIAL  CONSTITUENTS   OF  FOOD          491 


Unknown  but  Essential  Constituents  of  Pood. 

If  an  animal  is  fed  upon  a  mixture  of  pure  protein,  fat,  and 
carbohydrate,  with  a  due  admixture  of  salts  and  water,  it  does  not 
thrive,  but  shows  evidence  of  malnutrition,  although  the  quantities 
given  may  be  theoretically  correct.  If  a  growing  animal  is  fed  on 
such  a  diet  it  ceases  to  grow.  But  if,  as  Hopkins  showed  recently, 
a  small  amount  of  a  natural  food,  such  as  milk,  is  mixed  with  the 
artificial  diet  just  referred  to,  the  animals  thrive  and  grow  normally. 
There  is  something  extra,  something  which  is  at  present  unknown, 
which  is  absolutely  essential,  and  quite  small  amounts  of  it  are 
usually  sufficient. 

If  this  unknown  constituent  is  absent  from  a  man's  diet,  he 
undergoes  just  the  same  sort  of  malady,  and  illnesses  so  produced, 
such  as  scurvy  and  Beri-beri,  are  termed  "  Deficiency  diseases." 

A  good  deal  of  work  has  recently  been  done  in  relation  to  one 
of  these  diseases,  namely,  Beri-beri  (the  Kak-ka  of  Japan).  This 
is  prevalent  among  the  natives  whose  staple  article  of  diet  is 
polished  rice,  that  is,  rice  grains  deprived  of  their  external  layer. 
This  disease  is  characterised  by  malnutrition  of  the  nerves,  and 
neuritis  or  inflammation  of  the  nerves  is  followed  by  nerve-degenera- 
tion and  paralysis.  It  can  also  be  produced  in  birds  by  feeding 
them  on  polished  rice ;  and  in  both  man  and  bird  can  be  rapidly 
cured  by  adding  the  polishings  of  the  rice  grains.  The  outer  layer 
of  the  grain  contains  the  extra  something,  and  Funk  and  others  have 
recently  separated  out  from  the  polishings  a  base  which  they  have 
termed  vitamine,  although  at  present  there  is  no  certainty  of  its 
chemical  composition.  At  any  rate  this  base  is  the  curative 
principle,  and  very  small  doses  will  cure  the  condition. 

Vitamine  is  not  confined  to  rice  grains,  but  is  found  in  many 
other  vegetable  and  animal  foods.  The  value  of  whole  meal  bread, 
for  example,  does  not  depend  on  the  small  extra  amount  of  protein 
it  contains,  but  probably  here  also  upon  vitamine.  The  amount 
of  vitamine  varies  considerably.  Thus,  in  pigeons  fed  upon  polished 
rice,  as  much  as  20  grammes  of  meat  daily  must  be  added  to  prevent 
the  occurrence  of  Beri-beri ;  whereas  3  grammes  of  egg-yolk  are 
sufficient,  and  half  a  gramme  of  yeast  is  enough. 


OHAPTEK   XXXI 

THE  ALIMENTARY   CANAL;    SECRETING   GLANDS 

THE  alimentary  canal  consists  of  a  long  muscular  tube  lined  by 
mucous  membrane  beginning  at  the  mouth,  and  terminating  at  the 
anus.  It  comprises  the  mouth,  pharynx,  oesophagus  or  gullet,  stomach, 
small  intestine  and  large  intestine.  Opening  into  it  are  numerous 
glands  which  pour  juices  into  it;  these  bring  about  the  digestion  of 
the  food  as  it  passes  along.  Some  of  the  glands,  such  as  the  gastric 
and  intestinal  glands,  are  situated  in  the  mucous  membrane  which 
lines  the  canal;  others,  such  as  the  salivary  glands,  liver,  and  pan- 
creas, are  situated  at  a  distance  from  the  main  canal,  and  pour  their 
secretion  into  it  by  means  of  side  tubes  or  ducts. 

The  two  important  coats  in  the  wall  of  the  canal  are : — 

(1)  The  muscular  coat. — This  consists  of  two  layers ;  in  the  outer, 
the  fibres  are  arranged  longitudinally,  and  in  the  inner,  circularly. 
In  the  stomach  there  is  a  third  coat,  in  which  the  fibres  have  an 
oblique  direction.     At   the  cardiac  orifice  of  the  stomach  (that  is, 
where  the  oesophagus  enters)  and  at  its  pyloric  orifice  (that  is,  where 
the  small  intestine  leaves)  the  circular  fibres  are  increased  in  amount 
to  form  a  sphincter.     The  muscular  fibres  are  of  the  plain  variety, 
except  in  the  pharynx  and  upper  part  of  the  oesophagus  where  they 
are  striated.     A  nerve  plexus  (plexus  of  Auerbach,  fig.  100,  p.  79) 
is  situated  between  the  two  muscular  coats. 

(2)  The  mucous  membrane. — This  consists  of  an  epithelium  on  its 
surface;    this  is  stratified  in  mouth,  pharynx,  and  oesophagus,  but 
columnar  in  other  parts.     Beneath   the  epithelium  is  a  corium  of 
connective   tissue,   in   which   there   is   a   considerable   quantity  of 
lymphoid  tissue;  in  the  intestine  the  lymphoid  nodules  are  often 
spoken  of  as  solitary  follicles,  except  in  the  lower  part  of  the  small 
intestine  (the  ileum),  where  they  are  congregated  together  as  Peyer's 
patches.     At  the  back  of   the   mouth,   the   tonsils   are   masses   of 
lymphoid  nodules  covered  with  mucous  membrane.     In  the  deepest 
part  of  the  mucous  membrane  is  a  thin  layer  of  involuntary  muscle 
called  the  muscularis  mucosce. 

492 


CH.  XXXI.] 


THE   ALIMENTARY  CANAL 


493 


These  two  main  coats  (muscular  and  mucous)  are  connected 
together  by  a  loose  layer  of  connective  tissue  known  as  the  submucous 
coat.  In  this  the  larger  blood-vessels  are  situated  which  give  off 
branches  to  the  other  two  coats  but  more  abundantly  to  the  mucous 
membrane.  The  submucous  coat  also  contains  a  nerve  plexus  called 
the  plexus  of  Meissner.  In  the  stomach  and  intestines  there  is  a 
fourth  coat,  on  the  exterior,  derived  from  the  peritoneum  (serous  coat). 
The  secreting  glands  in  the  wall  of  the  alimentary  canal  are : — 
(1)  A  number  of  simple  little  mucous  glands  in  the  corium  of  the 
mucous  membrane  of  the  mouth,  pharynx,  and  oesophagus ;  their 
ducts  open  on  the  surface  (see  fig.  341). 


FIG.  341.— Section  of  the  mucous  membrane  and  submucous  coat  of  the  oesophagus, 
showing  mucous  glands. 

(2)  The  gastric  glands ;  these  are  tubular  glands  which  differ  in 
structure  in  different  regions  of  the  stomach,  and  which  we  shall 
consider  at  greater  length  in  our  description  of  gastric  digestion. 

(3)  The  glands  of  the  small  intestine.     Throughout  the  whole  of 
the  small  intestine  there  are   a'  large   number   of   simple   tubular 
glands  (lined  with  columnar  cells)  which  open  between  the  villi. 
They  are  called  the  crypts  of  Lieberkiihn.     In  the  first  part  of  the 


494 


THE   ALIMENTARY  CANAL ;    SECKETING   GLANDS      [CH.  XXXI. 


small  intestine,  known  as  the  duodenum,  an  additional  set  of  glands, 
called  the  glands  of  Brunner,  are  found.  They  are  imbedded  in  the 
submucous  coat,  and  the  duct  of  each  gland  passes  upwards  to  open 
on  the  surface  of  the  mucous  membrane.  Each  gland  is  a  branched 
and  convoluted  tube  lined  with  columnar  epithelium.  Fig.  342  shows 
these  two  kinds  of  glands,  and  also  the  villi  of  the  surface. 

Figs.  343  and  344  are  more  highly 
magnified  views  of  the  villi,  which 
increase  the  surface  of  the  small  intes- 
tine mainly  for  the  purpose  of  absorp- 
tion. A  villus  is  a  small  projection 
made  of  loose  lymphoid  tissue,  covered 
with  columnar  cells;  it  contains  in 
its  interior  a  plexus  of  blood-capillaries 
under  the  basement  membrane,  and  one 
or  more  commencing  lymphatic  vessels 
or  lacteals  situated  centrally. 


FIG.  342.— Vertical  section  of  duode- 
num, showing  a,  villi ;  ft,  crypts 
of  Lieberkuhn,  and  c,  Brunner's 
glands  in  the  submucosa  s,  with 
ducts,  d ;  muscularis  mucosae,  m ; 
and  circular  muscular  coat,  /. 
(Schofield.) 


FIG.  343.— Vertical  section  of  a  villus  of 
the  small  intestine  of  a  cat.  a, 
Striated  border  of  the  epithelium  ;  b, 
columnar  epithelium  ;  c,  goblet  cells ; 
d,  central  lymph-vessel;  e,  smooth 
muscular  fibres ;  /,  adenoid  stroma  of 
the  villus  in  which  lymph  corpuscles 
lie.  (Klein.) 


(4)  Glands  of  the  large  intestine.  Here  there  are  no  villi,  but 
the  crypts  of  Lieberkuhn  are  present  and  are  larger  than  in  the 
small  intestine.  Many  of  the  cells  lining  these  tubes  are  seen 
breaking  down  to  form  goblet  cells,  and  the  mucus  so  furnished  is 
the  main  substance  of  importance  secreted  in  this  part  of  the 
alimentary  canal. 

All  of  the  foregoing  glands  are  situated  in  the  wall  of  the 
alimentary  canal.  Those  situated  at  a  distance  from  it,  and  which 


CH.  XXXI.] 


SECRETING   GLANDS 


495 


pour  their  secretion  into  it  by  ducts,  are  the  salivary  glands, 
liver,  and  pancreas,  and  will  be  described  in  the  chapters  dealing 
with  those  organs. 

Before  passing  on  to  a  study  of  the  digestive  secretions  on  foods, 
we  may  consider  some  general  questions  relating  to  secreting  organs. 

It  is  the  function  of  gland-cells  to  produce  by  the  metabolism  of 
their  protoplasm  certain  substances  called  secretions.  These  materials 
are  of  two  kinds,  viz.,  those  which  are  employed  for  the  purpose  of 


Fio.  344.— A.  Villus  of  sheep.    B.  Villi  of  man,    (Slightly  altered  from  Teichmann.) 

serving  some  useful  office  in  the  economy,  and  those  which  are  dis- 
charged from  the  body  as  useless  or  injurious.  In  the  former  case 
the  separated  materials  are  termed  secretions  ;  in  the  latter  they  are 
termed  excretions. 

The  circumstances  of  their  formation,  and  their  final  destination, 
are,  however,  the  only  particulars  in  which  secretions  and  excretions 
can  be  distinguished ;  for,  in  general,  the  structure  of  the  parts 
engaged  in  eliminating  excretions  is  as  complex  as  that  of  the  parts 
concerned  in  the  formation  of  secretions.  It  will,  therefore,  be 
sufficient  to  speak  in  general  terms  of  the  process. 


496 


THE   ALIMENTARY   CANAL;    SECRETING   GLANDS      [CH.  XXXI. 


Every  secreting  apparatus  consists  essentially  of  a  layer  of  secret- 
ing cells  arranged  round  a  central  cavity ;  they  take  from  the  lymph 
which  bathes  them  the  necessary  material,  and  transform  it  into  the 
secretion  which  they  pour  at  high  pressure  into  the  cavity. 

In  the  case  of  the  glands  concerned  in  the  formation  of  the 
various  digestive  juices,  the  most  important  material  in  the  secretion 
is  an  enzyme  or  enzymes.  In  the  cells  which  form  the  enzyme,  it  is 
first  present  in  the  shape  of  a  pro-enzyme  or  zymogen.  The  trans- 
formation of  this  mother-substance  may  occur  before  or  during 
secretion,  as  is  the  case  for  ptyalin,  the  salivary  enzyme ;  or  after 


PIG.  345.— Transverse  section  through  four 
crypts  of  Lieberklihn  from  the  large 
intestine  of  the  pig.  They  are  lined 
by  columnar  epithelial  cells,  the 
nuclei  being  placed  in  the  outer  part 
of  the  cells.  The  divisions  between 
the  cells  are  seen  as  lines  radiating 
from  L,  the  lumen  of  the  crypt ;  o, 
epithelial  cells,  which  have  become 
transformed  into  goblet  cells,  x  350. 
(Klein  and  Noble  Smith.) 


FIG.  346.— A  gland 
of  Lieberkiihn  in 
longitudinal  sec- 
tion. (Brinton.) 


secretion,  as  is  the  case  for  trypsin,  one  of  the  most  important  of  the 
pancreatic  enzymes. 

Secreting  glands  may  be  classified  as  follows  : — 

1.  The  simple  tubular  gland  (A,  fig.  347),  examples  of  which  are 
furnished  by  the  crypts  of   Lieberkiihn  in  the  intestinal  wall.     To 
the  same  class  may  be  referred  the  elongated  and  tortuous  sudoriferous 
or  sweat  glands. 

2.  The   compound   tubular  glands   (D,    fig.    347)    form    another 
division.     These  consist   of    main    gland-tubes,   which    divide    and 
subdivide. 

3.  The  racemose  glands  are  those  in  which  a  number  of  vesicles 
or  acini  are  arranged  in  groups  or  lobules  (c,  fig.  347).     The  Meibo- 
mian  follicles  of   the   eyelids  are   examples  of   this  kind  of  gland. 
Some  glands,  like  the  pancreas,  are  of  a  mixed  character,  combining 
some  of  the  characters  of  the  tubular  with  others  of  the  racemose 
type ;  these  are  called  tubulo-racemose  or  tubulo-acinous  glands.    These 


CH.  XXXI.] 


SECRETING   GLANDS 


497 


glands  differ  from  each  other  only  in  secondary  points  of  structure, 
but  all  have  the  same  essential  character  in  consisting  of  rounded 
groups  of  vesicles  containing  gland-cells,  and  opening  by  a  common 
central  cavity  into  minute  ducts,  which  ducts  in  the  large  glands 


Fia.  347. — Diagram  of  types  of  secreting  glands.    A,  Simple  glands 


straight  tube  ;  h,  sac ;  i, 
c,  Racemose,  or  saccular 


coiled  tube.    B,  Multilociilar  crypts ;  k,  of  tubular  form  ;  I,  saccular. 

compound  gland  ;  m,  entire  gland,  showing  branched  duct  and  lobular  structure ;  n,   a  lobule, 

detached  with  o,  branch  of  duct  proceeding  from  it.    r>,  Compound  tubular  gland.    (Sharpey.) 

converge  and  unite  to  form  larger  and  larger  tubes,  and  at  length  open 
by  one  common  trunk  on  a  free  surface.  The  larger  racemose  glands, 
such  as  the  salivary  glands,  are  called  compound  racemose  glands. 


2  I 


CHAPTER   XXXII 


SALIVA 

THE  saliva  is  formed  by  three  pairs  of  salivary  glands,  called  the 
parotid,  submaxillary,  and  sublingual  glands. 

The  Salivary  Glands. 

These  typical  secreting  glands  are  made  up  of  lobules  united 
by  connective  tissue.  Each  lobule  is  made  of  a  group  of  tubulo- 
saccular  alveoli  or  acini,  from  which  a  duct  passes ;  this  unites  with 

other  ducts  to  form  larger  and  larger 
tubes,  the  main  duct  opening  into  the 
mouth. 

Each  alveolus  is  surrounded  by  a 
plexus  of  capillaries ;  the  lymph  which 
exudes  from  these  is  in  direct  contact 
with  the  basement  membrane  that  en- 
closes the  alveolus.  The  basement  mem- 
brane is  lined  by  secreting  cells  which 
surround  the  central  cavity  or  lumen. 
The  basement  membrane  is  thin  in 
many  places,  to  allow  the  lymph  more 
ready  access  to  the  secreting  cells;  it 
is  continued  along  the  ducts. 

The  secreting  cells  differ  according 
to  the  substance  they  secrete.  In  alveoli 
that  secrete  mucin  (such  as  those  in  the  sublingual  gland  and  some 
of  the  alveoli  in  the  submaxillary)  the  cells  after  treatment  with 
water  or  dilute  acid  are  clear  and  swollen  (fig.  350) ;  this  is  the 
appearance  they  usually  present  in  sections  of  the  organ.  But  if 
examined  in  their  natural  state  by  teasing  a  portion  of  the  fresh  gland 
in  serum,  they  are  seen  to  be  occupied  by  large  granules  composed 
of  a  substance  known  as  mucigen  or  mucinogen  (fig.  349).  When  the 
gland  is  active,  mucigen  is  transformed  into  mucin  and  discharged  as 


FIG.  318. — From  a  section  through  a 
salivary  gland,  a,  Serous  or  albumi- 
nous alveoli ;  b,  intralobular  duct 
cut  transversely.  (Klein  and  Noble 
Smith.) 


CH.  XXXII.] 


THE   SALIVARY   GLANDS 


499 


a  clear  droplet  of  that  substance  into  the  lumen  of  the  alveolus. 
Outside   these    are   smaller,    highly   granular    cells    containing    no 


Fio.  349.— Mucous  cells  from  submaxillary  gland  of  dog.  a,  from  a  resting  or  loaded  gland;  b,  from  a 
gland  which  has  been  secreting  for  some  time;  a',  b',  similar  cells  which  have  been  treated  with 
dilute  acid.  (Langley.)  (From  Quain's  Anatomy,  by  permission  of  Messrs  Longmans,  Green  &  Co.) 

mucigen ;  these  marginal  cells  stain  darkly,  and  generally  form 
crescentic  groups  (crescents  or  demilunes  of  Gianuzzi)  next  to 
the  basement  membrane.  They 
do  not  secrete  mucin,  but  are 
albuminous  cells.  After  secretion 
their  granules  are  lessened.  The 
demilunes  are  therefore  easily 
seen  in  the  gland  before  secretion, 
owing  to  the  contrast  they  ex- 
hibit to  the  cells  loaded  with 
mucin. 

In  those  alveoli  which  do  not 
secrete  mucin,  but  a  watery  non- 
viscid  saliva  (parotid,  and  some  of 
the  alveoli  of  the  submaxillary), 
the  cells  are  filled  with  small 
granules  of  albuminous  nature. 
Such  alveoli  are  called  serous  or 

albuminous,  to  distinguish  them  from  the  mucous  alveoli  we  have  just 
described. 

These  yield  to  the  secretion  its  enzyme,  ptyalin.  The  granular 
substance  within  the  cell  is  the  mother-substance  of  the  enzyme 
(zymogeri),  not  the  enzyme  itself.  It  is  converted  into  the  enzyme 
in  the  act  of  secretion.  We  shall  study  the  question  of  zymogcna 
more  fully  in  connection  with  the  gastric  glands  and  the  pancreas, 
where  they  have  been  separated  from  the  enzymes  by  chemical  methods. 
In  the  case  of  saliva  we  may  term  the  zymogen,  ptyalinogen  provision- 


Fio.  350.— Section  through  a  mucous  gland 
hardened  in  alcohol.  The  alveoli  are  lined 
with  mucous  cells,  and  outside  these  are  the 
demilunes.  (Heidenhain.) 


500 


SALIYA 


[CH.  XXXII. 


ally,  but  it  has  never  been  satisfactorily  separated  chemically  from 
ptyalin. 

After  secretion,  due  to  the  administration  of  food  or  of  such  a 
drug  as  pilocarpine,  the  cells  shrink,  they  stain  more  readily,  their 


FIG.  351.— Alveoli  of  parotid  gland.    A,  before  secretion ;  B,  in  the  first  stage  of  secretion  ;  C,  after 
prolonged  secretion.    (Langley.) 

nuclei  become  more  conspicuous,  and  the  outer  part  of  each  cell  becomes 
clear  and  free  from  granules  (fig.  351). 


The  Secretion  of  Saliva. 

The  process  of  secretion  consists  of  a  number  of  events  which 
may  be  divided  into  two  categories : — 

1.  The  transference  of  water  and  certain  substances  dissolved 

in  the  water  from  the  blood  of  the  surrounding  capillaries 
to  the  lumen  of  the  acinus. 

2.  The  modification  of  the  chemical  composition  of  this  solu- 

tion either  by  the  addition  to  it  of  substances  manu- 
factured by  the  gland-cells,  or  by  the  prevention  of 
substances  in  the  lymph  from  traversing  the  gland-cell 
and  reaching  the  lumen. 

In  regard  to  the  first  of  these,  we  must  regard  each  secreting  cell 
as  an  organ  which  pumps  the  water  through  its  own  substance  from 
the  lymph  space  to  the  lumen.  The  arrows  in  the  accompanying 
figure  (fig.  352)  show  the  direction  in  which  water  passes. 

The  result  of  this  pumping  action  is  fco  increase  the  pressure  in 
the  lumen,  and  diminish  that  in  the  lymph  space.  The  reduction  of 
pressure  in  the  lymph  space  causes  water  to  flow  into  it  through  the 
capillary  wall  from  the  blood,  and  this  filtration  is  further  helped  by 
a  rise  of  pressure  within  the  capillary,  for  during  secretion  the 
muscular  fibres  encircling  the  arteriole  wall  relax,  and  thus  the 
arterial  pressure  is  more  fully  communicated  to  the  capillary. 

The  extent  to  which  the  pressure  in  the  lumen  rises  depends 
upon  the  ease  with  which  the  secreted  fluid  can  pass  away  along 
the  duct,  and  if  the  saliva  is  made  to  run  up  a  vertical  tube  inserted 


CH.  XXXII.] 


THE   SECRETION   OF   SALIVA 


501 


into  the  duct,  it  may  reach  a  height  which  is  greater  than  the 
pressure  of  the  arterial  blood ;  this  is  an  experiment  which  disposes 
of  the  idea  that  the  sole  source  of  the  salivary  flow  is  the  blood- 
pressure,  for  there  is  in  addition  to  this  the  pumping  action  of  the 
secretory  cells.  Although  to  aid  the  imagination  we  roughly  compare 
the  cell  to  a  purnp,  we  have  no  real  knowledge  of  its  mechanism. 

--  Arteriole. 
'"Circular  Muscle  Fibres. 


Capillary. 

rV- Lymph  Space. 

I 

if— Gland  Cells. 

"Lumen. 


-Venule 


FIG.  352. — Diagram  of  a  secreting  acinus. 

Whatever  may  be  the  actual  mechanism,  we  are  nevertheless  quite 
sure  that  the  cells  really  do  active  work,  and  the  proofs  of  this  are 
the  following : — 

1.  Increase  of  work  finds  its  expression  in  increase  of  combustion. 
By  examining  the  gases  of  the  blood  leaving  the  gland,  it  is  found 
that  the  amounts  of  oxygen  used  and  carbonic  acid  produced  are 
increased  at  least  fourfold  when  saliva  is  being  actively  produced ; 
for  instance,  when  the  submaxillary  gland  is  thrown  into  action  by 
stimulation  of  its  secretory  nerve  (chorda  tympani). 

2.  It  may  be  proved  mathematically  that,  whenever  any  solution 
of  electrolytes  is  divided  into  two  solutions  each  differing  from  the 
original,  positive  work  must  be  done.     Salivary  secretion  is  a  case  in 
point ;  for  the  arterial  blood  is  changed  into  venous  blood  and  saliva, 
neither  of  which  has  the  same  composition  as  the  arterial  blood. 


502  SALIYA  [CH.  XXXII, 

The  loss  of  water  from  the  arterial  blood  can  be  calculated  by  examin- 
ing the  venous  blood,  and  finding  the  increase  in  the  concentration 
of  haemoglobin  there;  it  has  been  experimentally  proved  that  the 
amount  of  water  lost  from  the  blood  is  equal  to  the  quantity  of  saliva 
formed  in  a  given  time. 

We  now  pass  to  the  second  phase  of  secretion,  namely,  the  altera- 
tion in  the  composition  of  the  fluid.  The  cell  is  not  only  a  pumping 
engine  for  the  movement  of  water,  but  is  also  a  factory  of  organic 
substances  which  are  thrust  into  the  stream.  The  two  most  impor- 
tant of  these  materials,  though  neither  is  of  constant  occurrence,  are 
mucin,  and  the  enzyme  ptyalin.  On  the  other  hand,  the  cell  offers 
an  obstruction  to  the  passage  of  salts ;  the  saliva  is  therefore  poorer 
(and  the  lymph  in  the  lymph  space  correspondingly  richer)  in  salts 
than  the  blood.  The  accumulation  of  salts  in  the  lymph  is  an  addi- 
tional factor  in  attracting  (by  osmotic  pressure)  water  out  of  the 
blood.  Osmosis,  however,  is  only  a  contributory  cause  of  the  flow  of 
lymph;  it  will  not  account  for  secretion  of  saliva;  in  fact,  if  saliva 
and  blood  were  placed  in  an  osmometer,  fluid  would  pass  from  the 
saliva  to  the  blood. 

Secretory  Nerves  of  the  Salivary  Glands. 

The  submaxillary  gland  has  a  double  nerve-supply.  (1)  The 
chorda  tympani ;  this  is  a  branch  of  the  seventh  cranial  nerve,  and 
in  part  of  its  course  is  bound  up  in  the  same  sheath  as  the  lingual 
nerve,  a  branch  of  the  fifth.  When  the  lingual  nerve  crosses 
Wharton's  duct  beneath  the  tongue,  the  chorda  tympani  leaves  the 
lingual,  and  the  preganglionic  fibres  in  it  for  the  submaxillary  pass 
into  the  hilus  of  that  gland,  and  end  by  arborising  around  a  scattered 
collection  of  ganglion  cells  concealed  within  the  substance  of  the 
gland.  This  ganglion  is  known  as  Langley's  ganglion.  From  the 
cells  of  Langley's  ganglion  post-ganglionic  fibres  are  distributed  to 
the  gland-cells  and  also  to  the  blood-vessels. 

(2)  Sympathetic  branches  are  derived  from  the  plexus  around 
the  facial  artery  and  accompany  the  arterial  branches  which  supply 
the  gland.  (See  fig.  353.) 

The  chorda  tympani  is  par  excellence  the  secretory  nerve  of  the 
gland.  When  it  is  stimulated,  secretion  of  saliva  and  dilatation  of 
the  arterioles  take  place  invariably.  Stimulation  of  the  sympathetic 
always  produces  constriction  of  these  blood-vessels,  and  a  secretion 
of  a  small  .quantity  of  thick  viscid  saliva  may  also  occur,  but  often 
the  salivary  flow  is  entirely  absent.  Eecent  investigations  have 
shown  that  the  part  played  by  the  sympathetic  is  so  inconstant,  and 
the  results  obtained  by  different  methods  of  stimulation  (e.g., 
electrical,  and  the  administration  of  adrenaline)  are  so  different, 


CH.  XXXII.]        SECRETORY    NERVES    OF   SALIVARY   GLANDS 


503 


that  the  many  theories  formerly  advanced  of  the  relative  part 
played  by  the  two  nerves  must  be  regarded  as  mere  matters  of 
speculation. 

Section  of  the  chorda  tympani  produces  no  immediate  result ;  but  after  a  few 
days  a  scanty  but  continuous  secretion  of  thin  watery  saliva  takes  place ;  this  is 
called  paralytic  secretion.  If  the  operation  is  performed  on  one  side,  the  gland  of 
the  opposite  side  also  shows  a  similar  condition,  and  the  thin  saliva  secreted 
there  is  called  the  antUytic  secretion.  The  meaning  of  these  phenomena  is 
unknown. 

Effect  of  drugs  on  the  gland.     Atropine. — After  intravenous  injec- 
tion of  this  alkaloid  stimulation  of  the  chorda  tympani  no  longer 
produces  secretion  of  saliva.     Much 
larger  doses  are  necessary  to  abolish 
the  vaso -dilator  effect  of  chorda  stimu- 
lation, or  the  sympathetic  flow  in  those 
cases  where  previous  stimulation  of 
this    nerve    evoked    a    secretion    of 
saliva. 

Pilocarpine  produces  a  copious 
flow  of  saliva,  accompanied  by  vaso- 
dilatation. 

Ergotoxine  paralyses  the  effects  of 
sympathetic  stimulation,  but  not 
those  of  stimulation  of  the  chorda 
tympani. 

Adrenaline  produces  constriction 
of  the  blood-vessels.  In  some  animals 
it  evokes  a  considerable  flow  of  saliva, 
and  when  this  occurs  the  constriction 
of  the  vessels  is  followed  by  dilatation. 
This  favours  a  view  which  has  been 
advanced  by  some  observers,  that 
vaso-dilatation  is  in  part  produced  by 
the  chemical  action  of  the  products 
of  activity  (carbonic  and  lactic  acids,  etc.). 

The  sublingual  gland  is  innervated  by  the  same  nerves 
as  the  submaxillary,  but  the  preganglionic  fibres  of  the  chorda 
tympani  have  their  cell-station  in  the  so-called  submaxillary  ganglion 
which  is  situated  close  to  the  sublingual  gland  (see  fig.  353).  The 
submaxillary  ganglion  ought  properly  to  be  termed  the  sublingual 
ganglion.  This  has  been  determined  by  Langley's  nicotine  method 
(see  p.  200). 

The  parotid  gland  also  receives  two  sets  of  nerve-fibres  analogous 
to  those  we  have  studied  in  connection  with  the  submaxillary  gland. 
The  principal  secretory  nerve-fibres  are  glosso-pharyngeal  in  origin ; 


FIG.  353.— Diagram  of  secretory  nerves  of 
submaxillary  and  sublingual  glands. 
Two  fibres  of  the  chorda  tympani  (Ch.) 
are  shown,  one  of  which  supplies  the 
sublingual  gland,  of  which  an  acinus  is 
shown  ;  "the  cell-station  for  this  is  in  S. 
G.,  the  so-called  submaxillary  ganglion. 
The  other  fibre  supplies  an  acinus  of  the 
submaxillary  gland  ;  its  cell-station  is  in 
Langley's  ganglion  (L.  G.),  within  the 
substance  of  the  gland.  Sy.  is  a  fibre  of 
the  sympathetic,  which  has  its  cell- 
station  in  the  superior  cervical  ganglion, 
S.  C.  G.  (Alter  Dixon.) 


504  SALIYA  [GIL  xxxn. 

the  sympathetic  is  mainly  vasoconstrictor,  but  in  some  animals  it 
does  contain  a  few  secretory  fibres  also. 

Reflex  Secretion. — Under  ordinary  circumstances  the  secretion 
of  saliva  is  a  reflex  action.  The  principal  afferent  nerves  are  those  of 
taste ;  but  the  smell  or  sight  of  food  will  also  cause  "  the  mouth  to 
water " ;  and  under  certain  circumstances,  as  before  vomiting,  irrita- 
tion of  the  stomach  has  a  similar  effect.  These  sensory  nerves  stimu- 
late a  centre  in  the  medulla  from  which  efferent  secretory  impulses 
are  reflected  along  the  secretory  nerves  (chorda  tympani,  etc.)  to  the 
glands. 

Pawlow  has  recorded  some  interesting  observations  on  the  salivary 
glands.  He  made  an  external  fistula  of  the  submaxillary  duct  in  the 
dog,  and  found  that  the  sight  of  food,  the  smell  of  food,  or  the 
administration  of  any  kind  of  food,  caused  secretion;  acid  or  even 
sand  introduced  into  the  mouth  produced  a  similar  effect.  By  means 
of  similar  experiments  on  the  parotid  secretion,  very  different  results 
were  obtained.  If  the  dog  was  shown  meat,  or  the  meat  was  given 
to  it  to  eat,  there  was  practically  no  secretion.  If,  however,  the  meat 
was  given  as  a  dry  powder,  a  copious  secretion  followed ;  dry  bread 
produced  a  similar  effect ;  in  fact,  the  parotid  secretion  flows  freely 
if  dry  food  is  simply  shown  to  the  animal;  of  course,  in  all  such 
experiments  the  dog  must  be  hungry. 

Such  observations  emphasize  the  psychical  element  involved  in 
secretion,  and  point  out  also  the  adaptation  of  the  secretory  process 
to  the  needs  of  the  animal ;  thus  the  submaxillary  saliva,  which  is 
mainly  a  lubricant  in  virtue  of  its  mucin,  flows  whatever  the  food 
may  be,  whereas  moist  food  requiring  no  watery  saliva  from  the 
parotid  excites  the  flow  of  none. 

Extirpation  of  the  Salivary  Glands. — These  may  be  removed 
without  any  harmful  effects  in  the  lower  animals. 

The  Saliva. 

The  saliva  is  the  first  digestive  juice  to  come  in  contact  with  the 
food.  The  secretions  from  the  different  salivary  glands  are  mixed  in 
the  mouth ;  the  secretion  of  the  minute  mucous  glands  of  the  mouth 
and  a  certain  number  of  epithelial  scales  and  the  so-called  "  salivary 
corpuscles "  derived  from  the  tonsils  are  added  to  it.  The  liquid  is 
transparent,  slightly  opalescent,  of  slimy  consistency,  and  may  con- 
tain lumps  of  nearly  pure  mucin.  On  standing  it  becomes  cloudy 
owing  to  the  precipitation  of  calcium  carbonate,  the  carbonic  acid, 
which  held  it  in  solution  as  bicarbonate,  escaping. 

Of  the  three  forms  of  saliva  which  contribute  to  the  mixture 
found  in  the  mouth  the  sublingual  is  richest  in  solids  (2'75  per  cent.). 
The  submaxillary  saliva  comes  next  (21  to  2'5  per  cent.).  The 


CH.  XXXII.  ]  COMPOSITION   AND   ACTION   OF  SALIVA  505 

parotid  saliva  is  poorest  in  total  solids  (0'3  to  0*5  per  cent.),  and 
contains  no  mucin.  Mixed  saliva  contains  in  man  an  average  of 
about  0'5  per  cent,  of  solids  :  it  is  alkaline  in  reaction,  due  to  the  salts 
in  it  ;  and  has  a  specific  gravity  of  1002  to  1006. 

The  solid  constituents  dissolved  in  saliva  may  be  classified  thus  : 

(  a.  Mucin  :  this  may  be  precipitated  by  acetic  acid. 
_  J   b.  Ptyalin  :  an  amylolytic  enzyme. 

•1   c.  Protein  :  of  the  nature  of  a  globulin. 

V_  d.  Potassium  sulphocyanide. 

(  e.  Sodium  chloride  :  the  most  abundant  salt. 
Inorganic    .  -|  /.  Other  salts  :  sodium  carbonate,  calcium  phosphate  and 

\         carbonate  ;  magnesium  phosphate  ;  potassium  chloride. 

The  action  of  saliva  is  twofold,  physical  and  chemical. 

The  physical  use  of  saliva  consists  in  moistening  the  mucous 
membrane  of  the  mouth,  assisting  the  solution  of  soluble  substances 
in  the  food,  and  in  virtue  of  its  mucin,  lubricating  the  bolus  of  food 
to  facilitate  swallowing. 

The  chemical  action  of  saliva  is  due  to  its  active  principle,  ptyalin. 
This  substance  belongs  to  the  class  of  enzymes  which  are  called 
amylolytic  (starch-splitting)  or  diastatic  (resembling  diastase,  the 
similar  enzyme  in  germinating  barley  and  other  grains). 

The  starch  is  first  split  into  dextrin  and  maltose  ;  the  dextrin  is 
subsequently  converted  into  maltose  also  :  this  occurs  more  quickly 
with  erythro-dextrin,  which  gives  a  red  colour  with  iodine,  than  with 
the  other  variety  of  dextrin  called  achroo-dextrin,  which  gives  no 
colour  with  iodine.  Brown  and  Morris  give  the  following  equa- 
tion :  — 

4nH20 

[Water.] 


10(C6H1005)n  2 

[Starch.] 


.   4nC12H22O 

[Maltose.]  [Achroo-dextrin.]         [Erythro-dextrin.] 


1222u        (C6H1005)_   +   (C6HIOO6V 

Achroo-dextrin.]         [Erythro-dextrin.] 


Ptyalin  acts  in  a  similar  way,  but  more  slowly,  on  glycogen :  it  has 
no  action  on  cellulose;  hence  it  is  inoperative  on  uncooked  starch 
grains,  for  in  them  the  cellulose  layers  are  intact. 

Ptyalin  acts  best  at  about  the  temperature  of  the  body  (35-40°  C.). 
It  acts  best  in  a  neutral  medium ;  a  small  amount  of  alkali  makes 
but  little  difference ;  a  very  small  amount  of  acid  stops  its  activity. 
The  conversion  of  starch  into  sugar  by  swallowed  saliva  in  the 
stomach  continues  for  a  certain  time.  It  then  ceases  owing  to  the 
hydrochloric  acid  secreted  by  the  glands  of  the  stomach.  The  acid 
which  is  first  poured  out  neutralises  the  saliva,  and  combines  with 
the  proteins  of  the  food,  but  when  free  acid  appears  ptyalin  is  de- 
stroyed, and  so  it  cannot  resume  work  when  the  acid  is  neutralised 
in  the  duodenum.  Another  amylolytic  enzyme  contained  in  pan- 


506  SALIVA  [en.  xxxii. 

creatic  juice  (to  bo  considered  later)  continues  the  digestion  of  starch 
in  the  intestine. 

Cannon  has  shown  that  salivary  digestion  continues  in  the 
stomach  for  longer  than  one  supposed.  The  food  lying  in  the 
fundus  of  the  stomach  undergoes  amylolysis  for  at  least  two  hours, 
because  the  absence  of  peristalsis  in  this  region  until  quite  late 
stages  in  digestion  prevents  admixture  with  gastric  juice,  especially 
in  the  interior  of  the  swallowed  masses.  These  observations  were, 
however,  made  on  animals  in  a  quiescent  horizontal  position.  It  is 
extremely  doubtful  if  they  can  be  applied  to  man  in  a  vertical 
position,  especially  if  he  is  moving  about  (see  more  fully  Stomach 
movements  in  the  chapter  entitled  the  Mechanical  Processes  of 
Digestion). 


CHAPTER  XXXIII 

THE   GASTRIC   JUICE 

THE  juice  secreted  by  the  glands  in  the  mucous  membrane  of  the 
stomach  varies  in  composition  in  the  different  regions,  but  the  mixed 
gastric  juice,  as  it  may  be  termed,  is  a  solution  of  a  proteolytic 
or  proteoclastic  enzyme  called  pepsin  in  a  saline  solution,  which  also 
contains  a  little  free  hydrochloric  acid. 

The  gastric  juice  can  be  obtained  during  the  life  of  an  animal  by 
means  of  a  gastric  fistula.*  Gastric  fistulae  have  also  been  made  in 
human  beings,  either  by  accidental  injury  or  by  surgical  operations. 
The  most  celebrated  case  is  that  of  Alexis  St  Martin,  a  young 
Canadian,  who  received  a  musket  wound  in  the  abdomen  in  1822. 
Observations  made  on  him  by  Dr  Beaumont  formed  the  starting- 
point  for  our  correct  knowledge  of  the  physiology  of  the  stomach  and 
its  secretion. 

Artificial  gastric  juice  is  made  by  mixing  weak  hydrochloric  acid 
(0*2  per  cent.)  with  the  glycerin  extract  of  the  stomach  of  a  recently- 
killed  animal.  This  acts  like  the  normal  juice. 

When  examined  with  a  lens,  the  internal  or  free  surface  of  the 
stomach  presents  a  peculiar  honeycomb  appearance,  produced  by 
shallow  polygonal  depressions.  In  the  bottom  of  these  little  pits,  and 
to  some  extent  between  them,  minute  openings  are  visible,  which 
are  the  orifices  of  the  ducts  of  perpendicularly  arranged  tubular 
glands  (fig.  354),  imbedded  side  by  side  in  the  substance  of  the 
mucous  membrane. 

The  glands  of  the  mucous  membrane  are  of  three  varieties, 
(a)  Cardiac,  (&)  Fundus,  and  (c)  Pyloric. 

(a)  Cardiac  glands;  these  are  simple  tubular  glands  lined  by 
short  columnar  granular  cells,  and  are  only  found  quite  close  to  the 
cardiac  orifice. 

*  A  gastric  fistula  is  made  by  cutting  through  the  abdominal  wall  so  as  to 
expose  the  stomach.  The  stomach  is  then  attached  to  the  edges  of  the  abdominal 
wound,  and  a  small  orifice  is  finally  made  through  the  wall  of  the  stomach.  When 
the  wound  heals  there  is  then  a  free  communication  between  the  stomach  and  the 
exterior. 

507 


508 


THE  GASTRIC   JUICE 


[CH.  XXXIII. 


(b)  Fundus  glands  are  found  throughout  the  remainder  of  the 
cardiac  half  and   fund  us   of   the  stomach.     They   are   arranged  in 

groups  of  four  or  five,  which  are 
separated  by  a  fine  connective 
tissue.  Several  tubules  open  into 
one  duct,  which  forms  about  a 
third  of  the  whole  length  of  the 
tube  and  opens  on  the  surface. 
The  ducts  are  lined  with  columnar 
epithelium.  The  ^land-tubules  are 
lined  with  coarsely  granular  poly- 
hedral cells  (central  cells).  Between 
these  cells  and  the  basement  mem- 
brane of  the  tubes,  are  large  oval 
or  spherical  cells,  opaque  or  gran- 


FIG.  355.— Transverse  section  through 
lower  part  of  fundus  glands  of  a  cat. 
a,  Parietal  cells ;  6,  central  cells ; 
c,  transverse  section  of  capillaries. 
(Frey.) 

ular  in  appearance,  with  clear 
oval  nuclei,  bulging  out  the  base- 
ment membrane;  these  cells  are 
called  parietal  or  oxyntic  cells. 
They  do  not  form  a  continuous 
layer. 

(c)  Pyloric  Glands.  —  These 
glands  (fig.  356)  have  much  longer 
ducts  than  the  fundus  glands. 
Into  each  duct  two  or  three  tubules 
open  by  very  short  and  narrow 
necks,  and  the  body  of  each  tubule 
is  branched,  wavy,  and  convoluted. 
The  lumen  is  large.  The  ducts  are  lined  with  columnar  epithelium, 
and  the  tubules  with  shorter  and  finely  granular  cubical  cells, 
which  correspond  with  the  central  cells  of  the  fundus  glands. 
The  pyloric  glands  have  no  parietal  cells.  As  they  approach  the 


FIG.  354.— From  a  vertical  section  through  the 
mucous  membrane  of  the  cardiac  end  of 
stomach.  Two  fundus  glands  are  shown 
with  a  duct  common  to  both,  a,  Duct  with 
columnar  epithelium  becoming  shorter  as 
the  cells  are  traced  downward ;  n,  neck  of 
gland  tubes,  with  central  and  parietal  cells  ; 
b,  base  with  curved  caecal  extremity— the 
parietal  cells  are  not  so  numerous  here. 
(Klein  and  Noble  Smith.) 


CH.  XXXII I.] 


THE   GASTRIC    GLANDS 


509 


duodenum  the  pyloric  glands  become  larger,  more  convoluted  and 
more  deeply  situated.  They  are  directly  continuous  with  Brunner's 
glands  in  the  duodenum. 

The  central  cells  of  the  fundus  glands  and,  to  a  less  degree,  the 
cells  of  the  pyloric  glands,  are  loaded  with  granules.  During  secre- 
tion they  discharge  their  granules,  those  that  remain  being  chiefly 
situated  near  the  lumen,  leaving  in  each  cell  a  clear  outer  zone.  These 
are  the  cells  that  secrete  the  pepsin.  Like  secreting  cells  generally, 
they  pump  water  from  the  lymph  that  bathes  them  into  the  lumen ; 


FIG.  356.— Section  showing  the 
-  pyloric  glands,  s,  Free  sur- 
face ;  d,  ducts  of  pyloric  glands  ; 
n,  neck  of  same ;  m,  the  gland 
tubules ;  mm,  muscularis  mu- 
cosae.  (Klein  and  Noble  Smith.) 


FIG.  357.— Plan  of  the  blood-vessels  of  the 
stomach,  as  they  would  be  seen  in  a 
vertical  section,  a,  Arteries,  passing 
up  from  the  vessels  of  submucous 
coat ;  b,  capillaries  branching  between 
and  around  the  tubes ;  c,  superficial 
plexus  of  capillaries  occupying  the 
ridges  of  the  mucous  membrane; 
d,  vein  formed  by  the  union  of  veins 
which,  having  collected  the  blood  of 
the  superficial  capillary  plexus,  are 
seen  passing  down  between  the  tubes. 
(Brinton.) 


to  this  certain  materials  are  added  which  are  formed  by  the  proto- 
plasmic activity  of  the  cells.  The  most  important  substance  in  a 
digestive  secretion  is  the  enzyme.  In  the  case  of  the  gastric  juice 
this  is  pepsin.  We  can  trace  an  intermediate  step  in  this  process  by 
the  presence  of  the  granules  in  the  cells.  The  granules  are  not,  how- 
ever, composed  of  pepsin,  but  of  a  mother-substance  which  is  readily 
converted  into  pepsin.  We  shall  find  similar  enzyme  precursors  in 
the  cells  of  the  pancreas,  and  the  term  zymogen  is  applied  to  these 
enzyme  precursors.  The  zymogen  in  the  gastric  cells  is  called 
pepsinogen.  The  rennet-enzyme  that  causes  the  curdling  of  milk  is 
"formed  by  the  same  cells. 


510 


THE   GASTRIC   JUICE 


[CH.  XXX11I. 


The  parietal  cells  undergo  merely  a  change  of  size  during  secre- 
tion, being  at  first  somewhat  enlarged,  and  after  secretion  they  are 
somewhat  shrunken.  They  are  also  called  oxyntic  (acid -forming)  cells, 
because  they  secrete  the  hydrochloric  acid  of  the  juice.  Heidenhain 
succeeded  in  making  in  one  dog  a  cul-de-sac  of  the  fundus,  in  another, 
of  the  pyloric  region  of  the  stomach;  the  former  secreted  a  juice 
containing  both  acid  and  pepsin ;  the  latter,  parietal  cells  being 
absent,  secreted  a  viscid  alkaline  juice  containing  pepsin. 

The  formation  of  a  free  acid  from  the  alkaline  blood  and  lymph 
is  an  important  problem.  There  is  no  doubt  that  it  is  formed  from 
the  chlorides  of  the  blood  and  lymph,  and  of  the  many  theories 
advanced  as  to  its  actual  mode  of  formation,  none  is  wholly  satis- 
factory. Some  theories  are  chemical,  and  explain  the  formation  of 
the  acid  by  an  interaction  of  the  chlorides  and  phosphates.  Others 
call  to  their  assistance  the  law  of  "  mass  action,"  and  we  certainly 
know  that  by  the  action  of  large  quantities  of  carbonic  acid  on  salts 
of  mineral  acids,  the  latter  may  be  liberated  in  small  quantities.  We 
know  further  that  small  quantities  of  acid  ions  may  be  continually 
formed  in  the  organism  by  ionisation.  But  in  every  case  we  can 
only  make  use  of  these  explanations  if  we  assume  that  the  small 
quantities  of  acid  are  carried  away  as  soon  as  they  are  formed,  and 
thus  give  room  for  the  formation  of  fresh  acid.  Even  then  we  are 
unable  to  explain  the  whole  process.  A  specific  action  of  the  cells  is 
no  doubt  exerted,  for  these  reactions  can  hardly  be  considered  to 
occur  in  the  blood  generally,  but  rather  in  the  oxyntic  cells,  which 
possess  the  necessary  selective  powers  in  reference  to  the  saline 
constituents  of  the  blood,  and  the  hydrochloric  acid,  as  soon  as  it  is 
formed,  passes  into  the  secretion  of  the  gland  in  consequence  of  its 
high  power  of  diffusion. 

Composition  of  Gastric  Juice. 

The  following  table  gives  the  percentage  composition  of  the  gastric 
juice  of  man  and  the  dog: — 


Constituents. 

Human. 

Dog. 

Water  

99-44 

97-30 

Organic  substances  (chiefly  pepsin)    . 

0-32 
0'20 

1-71 
0'40  to  0'60 

CaCL,   , 

0'006 

0'06 

NaCf   . 

0*14 

0*25 

KC1      . 

0'05 

O'll 

NH4C1. 

0'05 

Ca3(PO4>2     . 

1 

0'17 

Mg(PO  2    . 

>       O'Ol 

0*02 

FeP04.        .        . 

O'OOS 

CH.  XXXIII.]  NERVES   OF   THE   GASTRIC   GLANDS  511 

One  sees  from  this  how  much  richer  in  all  constituents  the  gastric 
juice  of  the  dog  is  than  that  of  man.  Carnivorous  animals  have  always 
a  more  powerful  gastric  juice  than  other  animals ;  they  have  more 
work  for  it  to  do ;  but  the  great  contrast  seen  in  the  table  is,  no 
doubt,  partly  due  to  the  fact  that  the  persons  from  whom  it  has  been 
possible  to  collect  gastric  juice  have  been  invalids.  In  the  foregoing 
table  one  also  sees  the  great  preponderance  of  chlorides  over  other 
salts ;  apportioning  the  total  chlorine  to  the  various  metals  present, 
that  which  remains  over  must  be  combined  with  hydrogen  to  form 
the  free  hydrochloric  acid  of  the  juice. 

In  recent  years,  the  composition  and  action  of  the  gastric  juice 
has  been  studied  by  Pawlow.  By  an  ingenious  surgical  operation,  he 
succeeded  in  separating  from  the  stomach  of  dogs  a  diverticulum 
which  pours  its  secretion  through  an  opening  in  the  abdominal  wall ; 
the  nerves  of  this  small  stomach  are  intact,  and  the  amount  of  juice 
that  can  be  collected  from  it  when  it  is  active  amounts  to  several 
hundred  cubic  centimetres  in  a  few  hours.  Pawlow  thus  obtained  a 
pure  gastric  juice,  which  enabled  him  to  study  its  action  and  com- 
position. It  is  clear,  colourless,  has  a  specific  gravity  of  1003 — 1006, 
and  is  feebly  dextro-rotatory.  It  contains  0*4  to  0*6  per  cent,  of 
hydrochloric  acid.  It  is  strongly  proteolytic,  and  inverts  cane  sugar. 
When  cooled  to  0°  C.  it  deposits  a  precipitate  of  pepsin,  and  this 
carries  down  with  it  the  acid  in  loose  combination,  especially  in  the 
layers  first  deposited.  Its  percentage  composition  is  very  similar 
to  that  of  a  protein,  only  it  contains  chlorine  in  addition  to  the  usual 
elements.  The  numbers  agree  closely  with  those  obtained  by  Kiihne, 
who  used  ammonium  sulphate  as  the  precipitant. 

Pepsin  stands  apart  from  nearly  all  other  enzymes  by  requiring 
an  acid  medium  in  order  that  it  may  act.  A  compound  of  the  two 
substances,  called  pepsin-hydrochloric  acid>  is  the  really  active  agent. 
Other  acids  may  take  the  place  of  hydrochloric  acid,  but  none  act  so 
well.  Lactic  acid  is  often  found  in  gastric  juice:  this  is  derived  by 
fermentative  processes  from  the  food. 

The  digestive  powers  of  the  acids  are  proportional  to  their  dissociation  and  the 
number  of  H  ions  liberated.  The  anions,  however,  modify  this  by  having  different 
powers  of  retarding  the  action.  The  greater  suitability  of  hydrochloric  over  lactic 
acid,  for  instance,  in  gastric  digestion  is  due  to  the  fact  that  the  former  acid  more 
readily  undergoes  dissociation. 

The  Innervation  of  the  Gastric  Glands. 

As  long  ago  as  1852  Bidder  and  Schmidt  showed  in  a  dog  with 
a  gastric  fistula  that  the  sight  of  food  caused  a  secretion  of  gastric 
juice;  and  in  1878  Kichet  observed  that  in  a  man  with  complete 
occlusion  of  the  gullet  the  act  of  mastication  caused  a  copious  flow 
of  gastric  juice.  There  could  therefore  have  been  no  doubt  that  the 


512  THE   GASTKIC    JUICE  [CH.  XXXIII. 

glands  are  under  the  control  of  the  nervous  system,  but  the  early 
attempts  to  discover  the  secretory  nerves  of  the  stomach  were 
unsuccessful.  The  Kussian  physiologist  Pawlow  solved  the  problem 
by  the  employment  of  new  methods.  He  experimented  on  dogs. 
In  the  first  place  he  separated  off  the  diverticulum,  which  we 
described  on  the  last  page,  and  by  careful  experiments  he  showed  that 
the  secretion  of  this  small  stomach  is  an  exact  sample,  both  as  regards 
composition  and  rate  of  formation,  of  that  which  occurs  in  the  main 
stomach,  which  is  still  left  in  continuity  with  the  oesophagus  above 
and  the  duodenum  below. 

Another  procedure  adopted  was  to  divide  the  oesophagus,  and  to 
attach  the  two  cut  ends  to  the  opening  in  the  neck.  The  animal  was 
fed  by  the  lower  segment,  but  any  food  taken  into  the  mouth,  or  any 
saliva  secreted  there,  never  reached  the  stomach,  but  fell  out  through 
the  opening  of  the  upper  segment.  These  animals  were  kept  alive 
for  months,  and  soon  accommodated  themselves  to  their  new  con- 
ditions of  life.  The  animals  could  thus  be  subjected  to,  (1)  real 
feeding,  (2)  sham  feeding,  by  allowing  them  to  eat  food  which  subse- 
quently tumbled  out  through  the  neck  opening,  and  (3)  psychical 
feeding,  in  which  the  animal  was  shown  the  food  but  was  not  allowed 
to  eat  it.  The  psychical  element  is  important. 

Mechanical  excitation  of  the  stomach  wall  produces  no  secretion. 
If  water  is  introduced  there  is  a  slight  flow,  and  even  if  meat  is 
introduced  into  the  main  stomach  without  the  knowledge  of  the  dog, 
the  juice  formed  is  scanty  and  of  feeble  digestive  power. 

There  is,  moreover,  no  connection  between  the  acts  of  mastication 
and  swallowing  with  that  of  gastric  secretion.  Sham  feeding  with 
stones,  butter,  salt,  pepper,  mustard,  extract  of  meat,  and  acid,  though 
it  excited  a  flow  of  saliva,  produced  no  effect  on  the  stomach.  If, 
however,  meat  was  used  for  the  sham  feeding,  an  abundant  and  active 
secretion  occurred  in  the  stomach  (that  of  the  small  stomach  was 
actually  examined)  after  a  latency  of  about  five  minutes.  The 
secretion  is  thus  adapted  to  the  kind  of  food  the  dog  has  to  digest ; 
the  larger  the  proportion  of  protein  in  the  diet,  the  more  abundant  is 
the  juice,  and  the  richer  both  in  pepsin  and  acid. 

Indeed,  if  the  animal  is  hungry  and  shown  the  meat  and  not 
allowed  to  swallow  it,  the  effect  is  almost  as  great.  The  following 
striking  experiment  also  shows  the  importance  of  the  psychical  element. 
Two  dogs  were  taken,  and  a  weighed  amount  of  protein  introduced  into 
the  main  stomach  of  each  without  their  knowledge ;  one  was  then  sham 
fed  on  meat,  and  one  and  a  half  hours  later  the  amount  of  protein 
digested  by  this  dog  was  five  times  greater  than  that  which  was 
digested  by  the  other. 

In  the  meat,  however,  it  is  not  the  protein  which  acts  most 
strongly  as  the  stimulus ;  egg-white,  for  instance,  is  not  a  stronger 


CH.  XXXIII.]  ACTIONS   OF  GASTRIC   JUICE  513 

stimulus  than  water,  but  extract  of  meat  is  a  powerful  stimulus ; 
what  the  exact  extractives  are  that  act  in  this  way  is  not  yet  known, 
and  Herzen  has  since  shown  that  dextrin  acts  even  more  powerfully. 
Herzen  distinguishes  between  succagogues  (juice-drivers)  such  as  Liebig's 
extract,  and  peptogens  such  as  dextrin,  which  produce  not  only  an 
increased  flow,  but  a  juice  rich  in  pepsin -hydrochloric  acid.  The 
products  of  proteolysis  are  also  peptogenic,  so  that  when  once 
digestion  has  started,  a  stimulus  for  more  secretion  is  provided. 

If  the  vagi  are  cut  (below  the  origin  of  the  recurrent  laryngeal  to 
avoid  paralysis  of  the  larynx),  and  then  sham  feeding  is  performed 
with  meat,  no  secretion  is  obtained ;  the  vagi  therefore  contain  the 
secretory  fibres.  The  experiment  of  stimulating  the  peripheral  end 
of  the  cut  nerve  confirmed  this  hypothesis.  The  nerve  was  cut  in 
the  neck  four  or  five  days  before  it  was  stimulated;  in  this  time 
degeneration  of  the  cardio-inhibitory  fibres  took  place,  so  that 
stoppage  of  the  heart  did  not  occur  when  the  nerve  was  stimulated ; 
under  these  circumstances  a  secretion  was  obtained  with  a  long 
latency ;  the  latency  is  explained  by  the  presence  of  secreto-inhibitory 
fibres.  Atropine  abolishes  the  action  of  the  vagus.  In  other  animals 
the  spinal  cord  was  cut  at  the  level  of  the  first  cervical  nerve,  and  the 
animal  kept  alive  by  artificial  respiration ;  the  vagus  nerve  was  then 
cut,  and  its  peripheral  end  stimulated ;  an  abundant  secretion  usually 
followed.  Division  of  the  cord  renders  an  anaesthetic  unnecessary, 
and  also  prevents  the  afferent  impulses  set  up  by  the  operation  passing 
to  the  vagal  centres,  and  thus  exciting  the  inhibitory  impulses  which 
pass  down  the  vagus,  and  tend  to  prevent  secretion  under  ordinary 
circumstances. 

Pawlow  thinks  that  the  sympathetic  also  contains  some  secretory 
fibres,  but  this  has  not  yet  been  proved. 

Actions  of  Gastric  Juice. 

Gastric  juice  has  the  following  five  actions:— 

1.  It   is  antiseptic,  owing   to   the   hydrochloric   acid   present; 
putrefactive  processes  do  not  normally  occur  in  the  stomach,  and  the 
micro-organisms  which  produce  such  processes,  many  of  which  are 
swallowed  with  the  food,  are  in  great  measure  destroyed,  and  thus  the 
body  is  protected  from  them. 

2.  It  inverts  cane  sugar  into  dextrose  and  laevulose.     This  also 
is  due  to  the  acid  of  the  juice,  and  is  frequently  assisted  by  inverting 
enzymes  contained  in  the  vegetable  food  swallowed.     The  juice  has 
no  action  on  starch. 

3.  It  contains  lipase,  a  fat-splitting  enzyme.     The  protein  en- 
velopes of  the  fat  cells  are  first  dissolved  by  the  pepsin-hydrochloric 
acid,  and  the  solid  fats  are  melted.     They  are  then  split  in  small 
measure   into   their   constituents,   glycerin  and   fatty  acids.      This 

2   K 


514  THE  GASTRIC   JUICE  [CH.  XXXIII. 

action  is  mainly  produced  by  a  regurgitation  of  the  contents  of  the 
duodenum  mixed  with  pancreatic  juice ;  but  even  after  the  pylorus 
has  been  ligatured  and  regurgitation  prevented,  the  gastric  juice 
itself  produces  a  small  amount  of  fat-splitting,  and  therefore  con- 
tains lipase.  It  is  a  remarkable  fact  that  the  administration  of  fat 
in  the  food  increases  the  regurgitation  from  the  duodenum. 

4.  It  curdles  milk. — This  is  due  to  the  action  of  the  rennet 
enzyme  or  rennin.     The  conditions  of  this  action  we  have  already 
discussed  under  milk  (see  p.  482) ;  but  it  may  here  be  added  that 
Pawlow  has  advanced  the   view  that  rennin  is  not  a  distinct  and 
separate  enzyme,  but  milk-curdling  is  only  one  of  the  activities  of 
pepsin.     This  hypothesis  has  been  accepted  by  numerous  physio- 
logists ;  but,  on  the  other  hand,  there  is  a  number  of  equally  eminent 
observers  who  still  maintain  that  pepsin  and  rennin  are  two  separate 
enzymes.     Whichever  view  is  correct,  the  curd  of  casein  formed 
from  the  caseinogen  is  subsequently  digested  as  other  proteins  are. 

5.  It  is  proteolytic;    this  is  the  most  important  action  of  all. 
The  proteins  of  the  food  are  converted  by  the  pepsin-hydrochloric 
acid  into  peptones. 

This  action  is  a  process  of  hydrolysis;  and  peptones  may 
be  formed  by  other  hydrolysing  agencies,  such  as  superheated 
steam  or  heating  with  dilute  mineral  acids.  The  first  stage  in  the 
process  of  hydrolysis  is  that  of  acid  meta-protein,  formerly  called 
acid-albumin  or  syntonin;  the  next  step  is  the  formation  of 
propep tones  or  proteoses.  The  word  "  proteose  "  includes  the  albumoses 
(from  albumin),  globuloses  (from  globulin),  vitelloses  (from  vitellin), 
etc.  Similar  substances  are  also  formed  from  gelatin  (gelatinoses)  and 
elastin  (elastoses).  Then  peptone  (probably  a  mixture  of  polypeptides) 
is  produced.  The  products  of  digestion  of  protein  may  be  arranged 
according  to  the  order  in  which  they  are  formed,  as  follows : — 

1.  Acid  meta-protein. 

f  (a)  Proto-proteose   .  /  Th,£  Prim*ry  proteoses,  i.e., 

2.  Propeptone  I  (6)  Hetero-proteose  *ho.se    whlch    are   formed 
or  proteoses  1  ((j)  DeuterQ_  Qr  secondary    < 

proteose 

3.  Peptone. 

It  has  been  stated  that  the  prolonged  action  of  gastric  juice  leads 
to  the  further  splitting  of  the  peptone  into  amino-acids.  But  accurate 
work  has  shown  that  pepsin-hydrochloric  acid  does  not  split  any  of 
the  known  polypeptides  into  their  ultimate  cleavage  products. 

1.  Acid  meta-protein. — The  general  properties  of  the  meta- 
proteins,  the  first  degradation  products  in  the  cleavage  of  the 
proteins  which  occurs  during  digestion  are  described  on  p.  433.  We 
shall  find  later  that,  in  pancreatic  digestion,  an  alkali  meta-protein  is 
formed  instead  of  the  acid  modification. 


CII.  XXXIII. ] 


PRQTEOSES    AND    PEPTONES 


515 


2.  Proteoses. — They  are  not  coagulated  by  heat ;  they  are  pre- 
cipitated but  not  coagulated  by  alcohol :   like  peptone,  they  give  the 
pink  biuret  reaction.     They  are  precipitated  by  nitric  acid,  the  pre- 
cipitate being  soluble  on  heating,  and  reappearing  when  the  liquid  cools. 
This  last  is  a  distinctive  property  of  proteoses.     They  are  slightly 
diffusible. 

The  primary  proteoses  are  precipitated  by  saturation  with 
magnesium  sulphate  or  sodium  chloride.  Deutero-proteose  is  not; 
it  is,  however,  precipitated  by  saturation  with  ammonium  sulphate. 
Proto-  and  deutero-proteose  are  soluble  in  water ;  hetero-proteose  is 
not ;  it  requires  salt  to  hold  it  in  solution. 

3.  Peptones. — They  are  soluble  in  water,  are  not  coagulated  by  heat, 
and  are  not  precipitated  by  nitric  acid,  copper  sulphate,  ammonium 
sulphate,  and  a  number  of  other  precipitants  of  proteins.     They  are 
precipitated  but  not  coagulated  by  alcohol.     They  are  also  precipi- 
tated   by    tannin,    picric    acid,   potassio-mercuric    iodide,   phospho- 
molybdic  acid,  and  phospho-tungstic  acid. 

They  give  the  biuret  reaction  (rose-red  solution  with  a  trace  of 
copper  sulphate  and  caustic  potash  or  soda). 

Peptone  is  readily  diffusible  through  animal  membranes. 

The  annexed  table  will  give  us  at  a  glance  the  chief  characters  of 
peptones  and  proteoses  in  contrast  with  those  of  the  native  proteins, 
albumins,  and  globulins. 


Variety 
of 
proteid. 

Action 
of 
heat. 

Action 
of 
alcohol. 

Action 
of 
nitric  acid. 

Action  of 
ammonium 
sulphate. 

Action  of 
copper 
sulphate 
and  caustic 
potash. 

Diflusi- 
bility. 

Albumin 

Coagulated 

Precipitated, 
then    coagu- 

Precipitated 
in  the  cold  ; 

Precipitated 
by  complete 

Violet 
colour 

Nil 

lated 

not    readily 

saturation 

soluble      on 

heating 

Globulin 

Ditto 

Ditto 

Ditto 

Precipitated 

Ditto 

Ditto 

by  half  satu- 

ration;  also 

precipitated 

by  MgS04 

Proteoses 

Not 
coagulated 

Precipitated, 
but  not  co- 

Precipitated 
in  the  cold  ; 

Precipitated 
by      satura- 

Rose-red 
colour 

Slight 

agulated 

readily    sol- 

tion 

(biuret 

u  b  1  e       o  u 

reaction) 

heating;  the 

precipitate 

reappears  on 

cooling* 

Peptones 

Not 

coagulated 

Precipitated, 
but   not  co- 
agulated 

Not      precipi- 
tated 

Not      precipi- 
tated 

Rose-red 
colour 
(biuret 

Great 

reaction 

In  the  case  of  deutero-albumose  this  reac.ion  only  occurs  in  the  presence  of  «>xcess  of  salt. 


516  THE   GASTRIC   JUICE  [CH.  XXXIII. 

The  question  has  been  often  raised  why  the  stomach  does  not  digest  itself  during 
life.  The  mere  fact  that  the  tissues  are  alkaline  and  pepsin  requires  an  acid 
medium  in  which  to  act  is  not  an  explanation,  but  only  opens  up  a  fresh  difficulty 
as  to  why  the  pancreatic  juice  which  is  alkaline  does  not  digest  the  intestinal  wall. 
To  say  that  it  is  the  vital  properties  of  the  tissues  that  enable  them  to  resist 
digestion  only  shelves  the  difficulty  and  gives  no  real  explanation  of  the  mechanism 
of  defence.  Recent  studies  on  the  important  question  of  immunity  (see  p.  474) 
have  furnished  us  with  the  key  to  the  problem ;  just  as  poisons  introduced  from 
without  stimulate  the  cells  to  produce  antitoxins,  so  harmful  substances  produced 
within  the  body  are  provided  with  anti-substances  capable  of  neutralising  their 
effects  ;  for  this"  reason  the  blood  does  not  normally  clot  within  the  blood-vessels, 
and  Weinland  has  shown  that  the  gastric  epithelium  forms  an  antipepsin,  the 
intestinal  epithelium  an  antitrypsin,  and  so  on.  The  bodies  of  parasitic  worms  that 
live  in  the  intestine  are  particularly  rich  in  these  anti-bodies. 

Mett's  Tubes. 

A  method  which  is  now  generally  employed  for  estimating  the  proteolytic 
activity  of  a  digestive  juice  is  one  originally  introduced  by  MetL  Pieces  of 
capillary  glass-tubing  of  known  length  are  filled  with  white  of  egg.  This  is  set  into 
a  solid  by  heating  to  95°  C.  They  are  then  placed  in  the  digestive  fluid  at  36°  C., 
and  the  coagulated  egg-white  is  digested.  After  a  given  time  the  tubes  are 
removed  ;  and  if  the  digestive  process  has  not  gone  too  far,  only  a  part  of  the  little 
column  of  coagulated  protein  will  have  disappeared ;  the  length  of  the  remaining 
column  is  easily  measured,  and  the  length  that  has  been  digested  is  a  measure  of 
the  digestive  strength  of  the  fluid. 

Hamburger  has  used  the  same  method  in  investigating  the  digestive  action  of 
juices  on  gelatin.  The  tubes  are  filled  with  warm  gelatin  solution,  and  this  jellies 
on  cooling.  They  are  placed  as  before  in  the  digestive  mixture,  and  the  length  of 
the  column  that  disappears  can  be  easily  measured.  These  experiments  must,  how- 
ever, be  performed  at  room  temperature,  for  the  usual  temperature  (36° — 40°  C.)  at 
which  artificial  digestion  is  usually  carried  out  would  melt  the  gelatin.  He  has  also 
used  the  same  method  for  estimating  amylolytic  activity,  by  filling  the  tubes  with 
thick  starch  paste. 

Colour  Tests  for  Gastric  Acids. 

Hydrochloric  acid  is  absent  in  some  diseases  of  the  stomach,  notably  in 
cancer ;  many  colour  tests  for  hydrochloric  acid  have  been  introduced  from  time 
to  time,  but  by  far  the  most  characteristic  and  delicate  is  the  following : — 

Topfer's  test.  A  drop  of  dimethyl-amido-azo-benzol  is  spread  in  a  thin  film 
on  a  white  plate.  A  drop  of  dilute  hydrochloric  acid  (up  to  1  in  10,000)  strikes  with 
this  in  the  cold  a  bright  red  colour. 

Lactic  acid  is  soluble  in  ether,  and  is  generally  detected  by  making  an  ethereal 
extract  of  the  stomach  contents,  and  evaporating  the  ether.  If  lactic  acid  is  present 
in  the  residue  it  may  be  identified  by  the  following  way  : — 

A  solution  of  dilute  ferric  chloride  and  carbolic  acid  is  made  as  follows  : — 

10  c.c.  of  a  4-per-cent  solution  of  carbolic  acid. 

20  c.c.  of  distilled  water. 

1  drop  of  the  liquor  ferri  perchloridi  of  the  British  Pharmacopoeia. 

On  mixing  a  solution  containing  a  mere  trace  (up  to  1  part  in  10,000)  of  lactic 
acid  with  this  violet  solution,  it  is  instantly  turned  yellow.  Larger  percentages  of 
other  acids  (for  instance,  more  than  0'2  per  cent  of  hydrochloric  acid)  are  necessary 
to  decolorise  the  test  solution,  but  they  do  not  turn  the  solution  yellow. 

Another  colour  test,  that  of  Hopkins,  is  performed  as  follows :— 5  c.c.  of 
sulphuric  acid  and  3  drops  of  a  saturated  solution  of  copper  sulphate  are  added 
to  a  few  drops  of  lactic  acid  dissolved  in  alcohol.  The  mixture  is  placed  in  boiling 
water  for  five  minutes,  and  then  cooled;  2  drops  of  0'2  per  cent,  alcoholic  solution 
of  thiophene  are  then  added  ;  on  replacing  the  tube  in  boiling  water,  a  cherry-red 
colour  develops. 


CHAPTER  XXXIV 


DIGESTION   IN   THE   INTESTINES 

HERE  we  have  to  consider  the  action  of  pancreatic  juice,  of  bile,  and  of 
the  succus  entericus. 

The  Pancreas. 

This  is  a  tubulo-racemose  gland  closely  resembling  the  salivary 
glands  in  structure.     The  principal  differences  are  that  the  alveoli  or 
acini  are  more  tubular  in  character ; 
the  connective  tissue  between  them 
is    looser,    and     in     it    are    small 
groups  of  epithelium  cells  (islets  of 
Langerhans)  which  are  supplied  by  a 
close  network  of  capillaries  (fig.  359). 

The  secreting  cells  of  the 
pancreas  are  polyhedral.  When 
examined  in  the  fresh  condition,  or 
in  preparations  preserved  by  osmic 
acid,  their  protoplasm  is  seen  to  be 
filled  in  the  inner  two-thirds  with 
small  granules ;  but  the  outer  third 
is  left  clear,  and  stains  readily  with 
protoplasmic  dyes  (fig.  358). 

During  secretion  the  granules  are 
discharged ;  the  clear  zone  conse- 
quently becomes  wider,  and  the 
granular  zone  narrower. 

These  granules  indicate  the 
presence  of  a  zymogen  or  more 

probably  of  a  mixture  of  zymogens,  the  precursors  of  the  enzymes  in 
the  juice. 

In  the  centre  of  the  acini,  spindle-shaped  cells  (centro-acinar  cells) 
are  often  seen ;  their  function  and  origin  are  unknown. 

517 


FIG.  35S. — Section  of  the  pancreas  of  a  dog 
during  digestion,  a,  Alveoli  lined  with 
cells,  the  clear  outer  zone  of  which  is  well 
stained  with  haematoxylin  ;  d,  duct  lined 
with  short  cubical  cells,  x  350.  (Klein 
and  Noble  Smith.) 


518  DIGESTION    IN    THE   INTESTINES  [CII.  XXX1Y. 

Composition  and  Action  of  Pancreatic  Juice. 

The  pancreatic  juice  may  bo  obtained  by  a  fistula  in  animals,  a 
cannula  being  inserted  into  the  main  pancreatic  duct ;  but  as  in  the 
case  of  gastric  juice,  experiments  on  the  pancreatic  secretion  are 
frequently  performed  with  an  artificial  juice  made  by  mixing  a  weak 
alkaline  solution  (1  per  cent,  sodium  carbonate)  with  an  extract  of 
pancreas  which  is  usually  made  with  glycerin. 


Fio.  359.— Section  of  the  pancreas  of  armadillo,  showing  alveoli  and  an  islet  of  Langerhans  in  the 
connective  tissue.    (V.  1).  Harris.) 

Quantitative  analysis  of  human  pancreatic  juice  gives  the  follow- 
ing results : — 

Water 97 '6  per  cent. 

Organic  solids 1'8         ,, 

Inorganic  salts    .         .         .         .         .       0'6         ,, 

In  the  dog  the  amount  of  solids  is  much  greater. 
The  organic  substances  in  pancreatic  juice  are — 

(a)  Enzymes.     These  are  the  most  important  both  quantitatively 
and  functionally.     They  are  four  in  number : — 

i.  Trypsin,  a  proteolytic  or  proteoclastic  enzyme.     In  the  fresh 
juice,  however,  this  is  present  in  the  form  of  trypsinogen. 
ii.  Amylopsin,  an  amylolytic  (amyloclastic)  enzyme, 
iii.  Lipase,  a  fat-splitting  or  lipolytic  (lipoclastic)  enzyme, 
iv.  A  milk -curdling  enzyme. 

(b)  A  small  amount  of  protein  matter,  coagulable  by  heat. 

(c)  Traces  of  leucine,  tyrosine,  xan thine,  and  soaps. 
The  inorganic  substances  in  pancreatic  juice  are — 

e  Sodium  chloride,  which  is  the  most  abundant,  and  smaller  quan- 
tities of  potassium  chloride,  and  phosphates  of  sodium,  calcium,  and 


CH.  XXXIV.]  COMPOSITION   OF   PANCREATIC   JUICE  519 

magnesium.     The  alkalinity  of  the  juice  is  due  to  phosphates  and  car- 
bonates, especially  of  sodium. 

1.  Action  of  Trypsin. — Trypsin  acts  like  pepsin,  but  with  certain 
differences,  which  are  as  follows : — 

(a)  It  acts  in  an  alkaline,  pepsin  in  an  acid  medium. 

(&)  It  acts  more  rapidly  than  pepsin ;  deutero-proteoses  can  be 
detected  as  intermediate  products  in  the  formation  of  peptone ;  the 
primary  proteoses  have  not  been  detected. 

(c)  Alkali-meta-protein   is   formed   in   place   of   the   acid-meta- 
protein  of  gastric  digestion. 

(d)  It  acts  more  powerfully  on  certain  proteins  (such  as  elastin) 
which  are  difficult  of  digestion  in  gastric  juice.     It  does  not,  however, 
digest  collagen. 

(e)  Acting  on  solid  proteins  such  as  fibrin,  it  eats  them  away  from 
the  surface  to  the  interior ;  there  is  no  preliminary  swelling  as  in 
gastric  digestion. 

(/)  Trypsin  acts  further  than  pepsin,  and  rapidly  splits  up  the 
proteose  and  peptone  which  have  left  the  stomach  into  simpler  sub- 
stances, the  polypeptides.  The  polypeptides  in  their  turn  are  resolved 
into  their  constituent  amino-acids,  such  as  leucine,  tyrosine,  alanine, 
aspartic  acid,  glutamic  acid,  arginine,  tryptophane,  and  many  others. 
The  constitution  and  properties  of  these  cleavage  products  are 
described  on  pp.  417  to  422.  In  addition  to  these  there  is  a  certain 
amount  of  ammonia.  The  red  colour  which  a  tryptic  digest  strikes 
with  chlorine  or  bromine  water  is  due  to  the  presence  of  tryptophane 
(indole-amino-propionic  acid). 

When  once  the  peptone  stage  is  passed,  the  products  of  further- 
cleavage  no  longer  give  the  biuret  reaction ;  hence  they  are  frequently 
termed  abiuretic. 

A  variable  fraction  of  the  protein  molecule  is  broken  off  with 
comparative  ease,  so  that  certain  free  amino-acids  appear  in  the 
mixture,  at  a  time  when  the  remainder  are  still  linked  together  as 
polypeptides.  But  ultimately  the  whole  molecule  is  resolved  into 
amino-acids,  either  entirely  separated  or  in  very  short  polypeptide 
linkages. 

It  will  thus  be  seen  that  there  are  two  important  differences 
between  pepsin  and  trypsin ;  one  is  a  difference  of  degree,  trypsin 
being  by  far  the  more  powerful  and  rapid  catalyst;  the  second  is  a 
difference  of  kind,  pepsin  not  being  able  to  cleave  polypeptides  into 
amino-acids  in  the  way  trypsin  can.  The  preliminary  action  of 
pepsin,  however,  is  beneficial,  for  trypsin  cleavage  occurs  more  readily 
after  pepsin  has  acted  on  a  protein. 

2.  Action  of  Amylopsin. — The  conversion  of  starch  into  maltose 
is  the  most  rapid  of  all  the  actions  of  the  pancreatic  juice.     Its  power 
in  this  direction  is  much  greater  than  that  of  saliva,  and  it  will  act 


520  DIGESTION   IN   THE  INTESTINES  [GIL  XXXI V. 

even  on  unboiled  starch.  The  absence  of  this  enzyme  in  the  pancreatic 
juice  of  infants  is  an  indication  that  rnilk,  and  not  starch,  is  their 
natural  diet. 

3.  Action  on   Pats. — These  are  split  by  pancreatic  lipase  into 
glycerin  and  fatty  acids.     The  fatty  acids  unite  with  the  alkaline 
bases  present  to  form  soaps  (saponification,  see  p.  415).     If  a  glycerin 
extract  of  pancreas  is  filtered,  the  filtrate  has  no  lipoclastic  action ; 
the  material  deposited  on  the, filter  is  also  inactive,  but  on  mixing  it 
with  the  inactive  filtrate  once  more,  a  strongly  lipoclastic  material  is 
obtained.     In  this  way  lipase  is  separable  into  two  fractions:  the 
material  on  the  filter  is  inactive  lipase ;  the  material  in  the  filtrate 
is  its  co -enzyme ;  the  latter  is  not  destroyed  by  boiling.     Bile  salts 
also  activate  the  inactive  lipase,  and  this  explains  the  fact  that  bile 
favours  fat-splitting. 

Pancreatic  juice  also  assists  in  the  emulsification  of  fats ;  this  it 
is  able  to  do  because  it  is  alkaline,  and  it  is  capable  of  liberat- 
ing fatty  acids,  which  form  soaps  with  the  alkali  present;  the 
soap  forming  a  film  on  the  outer  surface  of  each  fat  globule 
prevents  them  running  together.  Emulsions  are  much  more 
permanent  in  the  presence  of  such  colloids  as  gum  or  protein.  The 
presence  of  protein  in  the  pancreatic  juice  renders  it  therefore 
specially  suitable  for  the  purpose  of  emulsification. 

4.  Milk-curdling  Enzyme. — The  addition  of  pancreatic  extracts 
or  pancreatic  juice  to  milk  causes  clotting ;  but  this  action  (which 
differs  in  some  particulars  from  the  clotting  caused  by  rennet)  can 
hardly  ever  be  called  into  play,  as  the  milk  upon  which  the  juice  has 
to  act  has  been  already  curdled  by  the  rennin  of  the  stomach. 

The  so-called  Peripheral  Reflex  Secretion  of  the  Pancreas. 

One  of  the  most  effective  ways  of  producing  a  flow  of  pancreatic 
juice  is  to  introduce  acid  into  the  duodenum.  Popielski  and 
Wertheimer  and  Le  Page  showed  that  this  flow  still  occurs  when  the 
nerves  supplying  the  duodenum  and  pancreas  have  been  cut  through. 
Wertheimer  also  mentions  that  the  flow  can  be  excited  by  injection 
of  acid  into  the  jejunum,  but  not  when  it  is  injected  into  the  lower 
part  of  the  ileum.  These  authors  concluded  that  the  secretion  is  a 
local  reflex,  the  centres  being  situated  in  the  scattered  ganglia  of  the 
pancreas,  or,  in  the  case  of  the  jejunum,  in  the  ganglia  of  the  solar 
plexus. 

This  subject  has  been  reinvestigated  by  Starling  and  Bayliss,  and 
the  results  they  have  obtained  are  most  noteworthy.  They  consider 
that  the  secretion  cannot  be  reflex,  since  it  occurs  after  extirpation  of 
the  solar  plexus,  and  destruction  of  all  nerves  passing  to  an  isolated 
loop  of  intestine.  Moreover,  atropine  does  not  paralyse  the  secretory 


CH.  XXXIV.]  SECRETION   OF  THE  PANCREAS  521 

action.  It  must  therefore  be  due  to  direct  excitation  of  the  pancreatic 
cells,  by  a  substance  or  substances  conveyed  to  the  gland  from  the 
bowel  by  the  blood-stream.  So  many  of  the  connections  between 
organs  are  made  by  nerves  (the  telegraphic  service  of  the  body),  that 
we  are  apt  to  forget  the  other  messenger,  the  blood,  whom  we  may 
compare  to  the  postman. 

The  exciting  substance  is  not  acid;  injection  of  04  per  cent,  of 
hydrochloric  acid  into  the  blood-stream  has  no  influence  on  the 
pancreas.  The  substance  in  question  must  be  produced  in  the 
intestinal  mucous  membrane  under  the  influence  of  the  acid.  This 
conclusion  was  confirmed  by  experiment.  If  the  mucous  membrane 
of  the  jejunum  or  duodenum  is  exposed  to  the  action  of  0'4  per  cent, 
hydrochloric  acid,  a  substance  is  produced  which,  when  injected  into 
the  blood-stream  in  minimal  doses,  produces  a  copious  secretion  of 
pancreatic  juice,  and  also,  but  to  a  less  extent,  of  bile.  This  substance 
is  termed  secretin.  It  is  associated  with  another  substance  which 
lowers  arterial  blood-pressure.  The  two  substances  are  not  identical, 
since  acid  extracts  of  the  lower  end  of  the  ileum  produce  a  lowering 
of  blood-pressure,  but  have  no  excitatory  influence  on  the  pancreas. 

Secretin  is  split  off  from  a  precursor,  pro-secretin,  which  is  present 
in  relatively  large  amounts  in  the  duodenal  mucous  membrane,  and 
gradually  diminishes  as  we  descend  the  intestine.  Pro-secretin  can 
be  dissolved  out  of  the  mucous  membrane  by  normal  saline  solution. 
It  has  no  influence  on  the  pancreatic  secretion.  Secretin  can  be  split 
off  from  it  by  boiling  or  by  treatment  with  acid. 

What  secretin  is  chemically  we  do  not  yet  know.  It  is  soluble  in 
alcohol  and  ether.  It  is  not  a  protein,  but  probably  is  an  organic 
substance  of  low  molecular  weight.  It  is,  moreover,  the  same  sub- 
stance in  all  animals,  and  not  specific  to  different  kinds  of  animals. 

Pawlow  by  experiments  of  a  similar  nature  to  those  which  led 
him  to  the  discovery  of  the  secretory  nerves  of  the  gastric  mucous 
membrane,  thought  he  had  also  discovered  the  secretory  nerves  of 
the  pancreas  in  the  vagus,  and  to  a  less  extent  in  the  splanchnic 
nerves.  His  failure  to  produce  this  result  in  some  experiments  he 
explained  by  the  concomitant  stimulation  of  secreto-inhibiting  fibres. 
It  is  quite  possible  that  nerves  of  this  nature  exist ;  but  Pawlow's 
experiments  do  not  prove  their  existence,  because  the  passage  of  acid 
chyme  into  the  duodenum  was  not  excluded,  and  so  he  may  only 
have  been  dealing  with  a  production  of  secretin,  the  chemical 
stimulus  to  pancreatic  activity. 

Starling's  work  on  secretin  naturally  led  him  and  others  to  seek 
for  other  chemical  messengers  employed  in  the  regulation  of  the 
activities  of  the  body,  and  it  has  already  been  established  that 
secretin  is  by  no  means  a  solitary  instance  of  such.  The  general 
name  given  to  these  agents  is  that  of  hormone.  The  chemical 


522  DIGESTION    IN   THE    INTESTINES  [CH.  XXXIV. 

substances  secreted  by  such  glands  as  the  thyroid  and  suprarenal 
must  be  included  under  this  term,  and  the  part  played  by  carbonic 
acid  in  the  regulation  of  breathing  (see  p.  380)  also  comes  into  the 
same  category.  In  our  study  of  gastric  digestion,  we  have  seen  the 
powerful  peptogenic  action  of  dextrin,  a  substance  formed  during 
the  salivary  digestion  of  starch ;  Edkins  has  given  the  name  gastrin 
to  the  special  hormone  which  is  the  result  of  the  action  of  the 
salivary  products  on  the  gastric  mucous  membrane.  Another 
example  of  a  hormone  is  furnished  by  the  material  formed  in  the 
ovary,  and  which,  passing  into  the  maternal  blood-stream,  stimulates 
the  mammary  gland  to  action. 

Adaptation  of  the  Pancreas. — To  a  certain  degree  it  cannot  be  doubted  that 
the  pancreas  adapts  its  secretion  to  the  work  it  has  to  do.  Thus,  whereas  gastric 
juice  has  a  maximal  flow  soon  after  the  ingestion  of  food,  the  pancreatic  flow 
does  not  attain  its  full  force  until  some  time  later,  that  is,  when  it  is  wanted.  The 
view  that  this  is  due  to  the  hormone  named  secretin,  which  is  not  formed  until 
the  gastric  contents  enter  the  intestine,  fully  explains  the  reason  for  the  delay. 

But  Pawlow  went  further  than  this,  and  stated  that  the  proportion  of  the 
various  enzymes  of  the  juice  was  adapted  to  the  proportions  of  proteins,  carbo- 
hydrates, and  fats  in  the  food  taken.  Considerable  doubt  has  been  cast  on  these 
results,  because  of  the  failure  to  confirm  one  of  the  most  remarkable  instances  of 
such  adaptation ;  this  is  the  power  of  the  pancreas  to  secrete  lactase  (an  enzyme 
capable  of  hydrolysing  lactose  into  glucoses).  Normal  pancreatic  juice  contains 
no  lactase,  but  certain  observers  stated  that  by  feeding  an  animal  on  milk,  the 
pancreas  could  be  educated  to  secrete  it.  Careful  experiments  by  Plimmer  have 
recently  shown  this  is  not  really  so,  and  so  much  more  stringent  experimental 
conditions  will  have  to  be  imposed  before  the  other  cases  of  adaptation  can  be 
considered  proven. 

Internal  Secretion  of  the  Pancreas— See  Diabetes,  next  chapter. 

The  Succus  Bntericus. 

Succus  entericus  has  been  obtained  free  from  other  secretions  by 
means  of  a  fistula.  Thiry's  method  is  to  cut  the  intestine  across  in 
two  places;  the  loop  so  cut  out  is  still  supplied  with  blood  and 
nerves,  as  its  mesentery  is  intact;  this  loop  is  emptied,  one  end  is 
sewn  up,  and  the  other  stitched  to  the  abdominal  wound,  and  so  a 
cul-de-sac  from  which  the  secretion  can  be  collected  is  made.  The 
continuity  of  the  remainder  of  the  intestine  is  restored  by  fastening 
together  the  upper  and  lower  portions  of  the  bowel  from  which  the 
loop  has  been  removed.  Vella's  method  resembles  Thiry's,  except  that 
both  ends  of  the  loop  are  sutured  to  the  wound  in  the  abdomen.  Fig. 
360  illustrates  the  two  methods. 

The  succus  entericus  possesses  the  power  of  converting  disaccha- 
rides  into  monosaccharides.  This  power  it  owes  to  three  enzymes. 
Invertase  or  sucrase  is  the  enzyme  which  inverts  cane  sugar — that  is,  it 
converts  cane  sugar  into  dextrose  and  laevulose.  The  original  use  of  the 
term  "  inversion  "  has  been  explained  on  p.  410.  It  may  be  extended  to 
include  the  similar  hydrolysis  of  other  disaccharides,  although  there 


CH.  XXXIV.] 


THE  SUCCUS  ENTERICUS 


523 


may  be  no  formation  of  laevo-rotatory  substances.  The  enzyme 
in  the  juice  which  converts  maltose  into  dextrose  is  called  maltase ; 
and  that  which  acts  upon  lactose  is  called  lactase. 

Up  till  a  few  years  ago  little  or  nothing  was  known  regarding 
the  action  of  the  intestinal  juice  beyond  this,  but  investigations 
published  since  that  time  have  altered  this  state  of  things,  and  in  the 
light  of  these  the  succus  entericus  is  seen  to  be  a  juice  of  the  highest 
importance. 

Pawlow  was  the  first  to  show  that  one  of  its  main  actions  is  to 
reinforce  and  intensify  the  action  of  the  pancreatic  juice,  especially 
in  reference  to  its  proteolytic  power.  Fresh  pancreatic  juice  has 
practically  no  digestive  power  on  proteins.  Claude  Bernard,  the 
earliest  to  study  the  pancreatic  secretion,  entirely  missed  its  tryptic 
action.  On  standing,  the  juice  very  slowly  acquires  proteolytic 
activity.  Yernon  has  shown  that  much  the  same  is  true  for  extracts 
of  the  pancreas.  There  is  no  doubt  that  what  the  fresh  juice  con- 


II 


FIG.  360.— Diagram  of  intestinal  fistula.    I.,  Thiry's  method  ;  II.,  Vella's  method.    A,  Abdominal  wall ; 
B,  intestine,  with  mesentery ;  C,  separated  loop  of  intestine,  with  attached  mesentery. 

tains  is  trypsinogen,  and  this  is  slowly  transformed  into  the  active 
enzyme  trypsin. 

If  fresh  pancreatic  and  intestinal  juices  are  mixed  together,  the 
result  is  a  powerful  proteolytic  mixture,  though  neither  juice  by  itself 
has  any  proteolytic  activity. 

Pawlow  speaks  of  the  substance  in  the  intestinal  juice  which  has 
this  action  as  an  "enzyme  of  enzymes,"  and  has  named  it  entero- 
kinase. 

Starling,  like  Pawlow,  worked  with  dogs,  and  has  confirmed  his 
main  results.  A  valuable  contribution  to  the  same  subject  has  also 
been  made  by  Hamburger.  He  has  had  the  unusual  opportunity  of 
examining  human  succus  entericus.  It  became  necessary  in  a  patient 
for  surgical  reasons  to  isolate  a  loop  of  the  small  intestine,  and  this 
loop  continued  to  discharge  intestinal  juice  to  the  exterior  for  some 


52-4  DIGESTION   IN    THE   INTESTINES  [CH.  XXXIV. 

time  after  the  operation.  He  found  that  this  juice,  like  that  of  the 
dog,  contains  a  substance  which  renders  pancreatic  juice  active.  He 
could  not  find  that  it  exercised  any  activating  influence  on  the 
fat-splitting  and  amylolytic  enzymes  of  the  pancreas,  but  its  action 
on  the  tryptic  enzyme  was  most  marked.  His  quantitative  experi- 
ments do  not  bear  out  Pawlow's  view  that  the  active  substance 
in  the  intestinal  juice  is  an  enzyme,  for  it  is  unable,  like  an  enzyme, 
to  act  on  an  unlimited  amount  of  pancreatic  juice.  Starling,  however, 
supports  Pawlow's  view ;  provided  sufficient  time  is  allowed  to 
elapse,  it  will  activate  any  amount  of  pancreatic  juice. 

Delezenne  has  advanced  a  hypothesis  on  the  lines  of  Ehrlich's 
explanation  of  the  action  of  hsemolysins  (see  p.  475).  He  regards 
trypsinogen  as  the  amboceptor  which  enables  the  enterokinase  to 
become  effective. 

Starling's  subsequent  work  did  not  support  this  view.  We 
may  therefore  best  explain  the  action  of  enterokinase  as  an 
activating  agent,  by  the  fact  that  it  is  capable  of  transforming  the 
zymogen  trypsinogen  into  the  effective  enzyme  trypsin.  How  it  does 
this  is  explained  by  J.  Mellanby  and  Woolley  in  the  following 
way : — Trypsinogen  is  a  complex  consisting  of  trypsin  united  by  a 
protein  moiety,  and  so  long  as  the  enzyme  is  combined  in  this  way 
it  is  inactive ;  enterokinase  is  a  proteoly tic  enzyme  which  adsorbs 
and  then  digests  this  protein  moiety,  and  thus  liberates  the  trypsin. 

The  mixture  of  pancreatic  and  intestinal  juice  is  extraordinarily 
powerful.  If  secretin  is  administered  to  a  fasting  animal,  the  juice 
secreted,  having  no  food  to  act  upon,  will  produce  erosion  and 
inflammation  of  the  intestinal  wall.  (Starling.) 

Dixon  and  Hamill's  recent  work  has  made  clearer  the  mechanism 
of  pancreatic  secretion.  There  are  in  the  pancreas  three  precursors 
of  enzymes,  namely,  protrypsinogen,  proamylopsin,  and  prolipase. 
Secretin  combines  chemically,  or  at  any  rate  acts  chemically,  on  all 
three ;  it  liberates  amylopsin  and  lipase  from  their  precursors,  and 
these  two  active  enzymes  pass  into  the  pancreatic  juice.  It  liberates 
trypsinogen  from  protrypsinogen,  and  trypsinogen  passes  into  the 
juice;  finally  trypsinogen  is  converted  into  the  active  enzyme  trypsin 
by  the  enterokinase  of  the  succus  entericus. 

Another  discovery  in  connection  with  succus  entericus  has  been 
made  by  Otto  Cohnheim.  The  juice  has  no  action  on  native  proteins 
such  as  fibrin  and  egg-white,  but  it  acts  on  proteoses  and  peptone. 
It  rapidly  breaks  them  up  into  simpler  substances,  of  which  ammonia, 
leucine,  tyrosine,  and  the  hexone  bases  have  been  identified.  Cohn- 
heim has  named  the  enzyme  to  which  this  is  due  erepsin.  Ham- 
burger found  that  erepsin  is  also  present  in  the  human  juice ;  it  is 
not  identical  with  enterokinase,  because  erepsin  is  destroyed  by  heat- 
ing the  juice  to  59°  C.  for  three  hours ;  enterokinase  is  not  destroyed 


GIL  XXXIV.]  BACTERIAL   ACTION  525 

until  the  temperature  is  raised  to  67°  C.  Other  observers  have  con- 
firmed the  discovery  of  erepsin,  but  have  found  that  it  or  a  similar 
enzyme  is  present  in  most  tissues;  it  is  most  abundant  in  the 
kidney  (Vernon). 

Cohnheim  has  investigated  the  action  of  erepsin  on  a  large 
number  of  proteins;  it  acts  energetically  on  proteoses,  peptone,  and 
protamines:  on  histone,  which  occupies  an  intermediate  place 
between  protamines  and  the  other  proteins,  it  has  a  slight  action. 
On  the  other  native  proteins  it  has  no  action,  with  the  single  excep- 
tion of  caseinogen,  which  is  speedily  broken  up  into  simple  sub- 
stances ;  thus  opens  up  the  interesting  physiological  possibility  that 
the  suckling  infant  is  able  to  digest  its  protein  nutriment  even  if 
pepsin  and  trypsin  are  absent. 

The  bile,  as  .we  shall  find,  has  little  or  no  digestive  action  by 
itself,  but  combined  with  pancreatic  juice  it  assists  the  latter  in  all 
its  actions.  This  is  true  for  the  digestion  of  starch  and  of  protein, 
but  most  markedly  so  for  the  digestion  of  fat.  Occlusion  of  the  bile- 
duct  by  a  gall-stone  or  by  inflammation  prevents  bile  entering  the 
duodenum.  Under  these  circumstances  the  fceces  contain  a  large 
amount  of  undigested  fat. 

The  importance  of  the  work  of  Pawlow,  and  the  other  physi- 
ologists whose  names  have  been  mentioned,  arises  from  the  entirely 
new  light  thrown  upon  the  digestion  process  as  a  whole.  We  have 
been  too  apt  to  think  of  the  occurrences  in  the  alimentary  canal  as  a 
series  of  isolated  phenomena.  We  now  see  that  each  step  follows  in 
an  orderly  manner  as  the  result  of  the  previous  steps.  For  example, 
the  acid  gastric  juice  reaches  the  small  intestine,  and  there  produces 
secfetin  from  its  forerunner ;  the  secretinis  taken  by  the  blood -stream 
to  the  pancreas,  where  it  excites  a  flow  of  pancreatic  juice;  this  juice 
arrives  in  the  duodenum  ready  to  act  on  starchy  substances  and  on 
fat.  With  the  assistance  of  the  bile,  fatty  acid  is  liberated  which  in 
its  turn  forms  more  secretin,  and  so  more  pancreatic  juice.  The 
pancreatic  juice,  however,  cannot  act  on  proteins  without  enterokinase, 
which  is  supplied  by  the  succus  entericus ;  this  sets  free  the  trypsin  ; 
and  trypsin  with  the  assistance  of  erepsin  effectively  carries  out 
digestive  proteolysis. 

Bacterial  Action. 

The  gastric  juice  is  an  antiseptic ;  the  pancreatic  juice  is  not. 
An  alkaline  fluid  like  pancreatic  juice  is  just  the  most  suitable  medium 
for  bacteria  to  flourish  in.  Even  in  an  artificial  digestion  the  fluid 
is  very  soon  putrid,  unless  special  precautions  to  exclude  or  kill 
bacteria  are  taken.  It  is  often  difficult  to  say  where  pancreatic 
action  ends  and  bacterial  action  begins,  as  many  of  the  bacteria  that 
grow  in  the  intestinal  contents  (having  reached  that  situation  in 


526  DIGESTION   IN   THE   INTESTINES  [CH.  XXXIV. 

spite  of  the  gastric  juice)  produce  enzymes  which  act  in  the  same 
way  as  the  pancreatic  juice.  Some  form  sugar  from  starch,  others 
peptone,  and  amino-acids  from  proteins,  while  others,  again,  break 
up  fats.  There  are,  however,  certain  actions  that  are  entirely  due 
to  these  putrefactive  organisms. 

i.  On  carbohydrates.  The  most  frequent  fermentation  they  set 
up  is  the  lactic  acid  fermentation  :  this  may  go  further  and  result  in 
the  formation  of  carbonic  acid,  hydrogen,  and  butyric  acid  (see  p. 
411).  Cellulose  is  broken  up  into  carbonic  acid  and  methane.  This 
is  the  chief  cause  of  the  gases  in  the  intestine,  the  amount  of  which 
is  increased  by  vegetable  food. 

ii.  On  fats.  In  addition  to  acting  like  lipase,  they  produce 
lower  acids  (valeric,  butyric,  etc.).  The  formation  of  acid  products 
from  fats  and  carbohydrates  gives  to  the  intestinal  contents  an  acid 
reaction.  Eecent  researches  show  that  the  contents  of  the  intestine 
become  acid  much  higher  up  than  was  formerly  supposed.  Organic 
acids  do  not,  however,  hinder  pancreatic  digestion. 

iii.  On  proteins.  Peptones,  amino-acids,  and  ammonia  are  pro- 
duced; but  the  enzymes  of  these  putrefactive  organisms  have  a 
specially  powerful  action  in  liberating  substances  having  an  evil 
odour,  such  as  indole  (C8H7N),  skatole  (C9H9N),  and  phenol  (C6H60). 
Indole  and  skatole  originate  from  the  trytophane  radical  of  proteins. 
There  are  also  gaseous  products  in  some  cases. 

Ammonia-producing  organisms  nourish  best  in  the  lower  regions 
of  the  small  intestine;  the  ammonia  neutralises  the  organic  acids 
produced  higher  up,  and  in  the  large  intestine  the  contents  have 
in  consequence  an  alkaline  reaction. 

If  excessive,  putrefactive  processes  are  harmful ;  if  within  normal 
limits,  they  are  useful,  helping  the  pancreatic  juice,  and,  further, 
preventing  the  entrance  into  the  body  of  poisonous  products.  It  is 
possible  that,  in  digestion,  poisonous  alkaloids  are  formed.  Certainly 
this  is  so  in  one  well-known  case.  Lecithin,  a  material  contained  in 
small  quantities  in  many  foods,  and  in  large  quantities  in  egg-yolk 
and  brain,  is  broken  up  by  the  pancreatic  juice  into  glycero- 
phosphoric  acid,  fatty  acids,  and  an  alkaloid  called  choline.  We 
are,  however,  protected  from  the  poisonous  action  of  choline  by  the 
bacterial  enzymes,  which  break  it  up  into  carbonic  acid,  methane,  and 
ammonia. 

Sour  milk  has  been  recently  extolled  not  only  as  a  useful  food, 
but  as  a  cure  for  many  dyspeptic  disorders.  Although  its  efficacy  in 
this  direction  has  been  much  exaggerated,  its  usefulness  in  certain 
cases  is  explicable  on  the  ground  that  the  lactic  acid  bacillus,  which 
is  a  harmless  one  in  itself,  possesses  the  power,  when  it  is  actively 
growing,  of  destroying  other  micro-organisms  of  a  more  harmful 
kind. 


CHAPTER  XXXV 


THE   LIVER 


THE  Liver,  the  largest  gland  in  the  body,  is  an  extremely  vascular 
organ,  and  receives  its  supply  of  blood  from  two  sources,  viz.,  from 
the  portal  vein  and  from  the  hepatic  artery,  while  the  blood  is 
returned  from  it  into  the  vena  cava  inferior  by  the  hepatic  veins. 


o.v, 


FIG.  361.— The  under  surface  of  the  liver.  G.  B.,  Gall-bladder ;  H.  D.,  common  bile-duct ;  H.  A.,  hepatic 
artery  ;  v.  p.,  portal  vein ;  L.  Q.,  lobulus  quadratus  ;  L.  s.,  lobulus  spigelii  ;  L.  c.,  lobulus  caudatus  ; 
D.  v.,  ductus  venosus ;  u.  r.,  umbilical  vein.  (Noble  Smith.) 

Its  secretion,  the  Hie,  is  conveyed  from  it  by  the  hepatic  duct,  either 
directly  into  the  intestine,  or,  when  digestion  is  not  going  on,  into 
the  cystic  duct,  and  thence  into  the  gall-bladder,  where  it  accumu- 
lates until  required. 

The  liver  is  in  origin  a  tubular  gland,  but  as  development  pro- 
gresses it  soon  loses  all  resemblance  to  the  tubular  glands  found 
elsewhere.  It  is  made  up  of  small  roundish  or  oval  portions  called 
lobules,  each  of  which  is  about  ^V  of  an  inch  (about  1  mm.)  in 
diameter,  and  composed  of  the  liver  cells,  between  which  the  blood- 
vessels and  bile-vessels  ramify.  The  hepatic  cells  (fig.  364),  which 
form  the  glandular  or  secreting  part  of  the  liver,  are  of  a  spheroidal 

527 


528 


THE   LIVEK 


[CH.  XXXV. 


form,  but  somewhat  polygonal  from  mutual  pressure.  Each  possesses 
a  nucleus,  sometimes  two.  The  cell  protoplasm  contains  numerous 
fatty  particles,  as  well  as  a  variable  amount  of  glycogen. 

The  portal  vein,  hepatic 
artery,  and  hepatic  duct,  run 
in  company,  and  their  appear- 
ance on  longitudinal  section  is 
shown  in  fig.  362.  Eunning 
together  through  the  substance 
of  the  liver,  they  are  contained 
in  small  channels  called  portal 
canals,  their  immediate  in  vest- 
ment being  a  sheath  of  areolar 
tissue  continuous  with  Glis- 
son's  capsule. 

In  its  course  through  the 
liver  the  portal  vein  gives  off 
small  branches  which  divide 
and  subdivide  between  the 
lobules  surrounding  them  and 
limiting  them,  and  from  this 
circumstance  called  inter- 
lobular  veins.  From  these 
vessels  a  dense  capillary  net- 
WOrk  is  prolonged  into  the 
i  .  is  J_T_  i  i_  i 

substance  of  the  lobule,  and 
this  network  converges  to  a 

single  small  vein,  occupying  the  centre  of  the  lobule,  and  hence 
called  m^ra-lobular.  This  arrangement  is  well  seen  in  fig.  363, 
which  represents  a  section  of  a  small  piece  of  an  injected  liver. 

The  m£ra-lobular  veins  discharge  their  contents  into  veins  called 
sw&-lobular;  these  by  their  union,  form  the  main  branches  of  the 
hepatic  veins,  which  leave  the  posterior  border  of  the  liver  to  end 
by  two  or  three  principal  trunks  in  the  inferior  vena  cava,  just 
before  its  passage  through  the  diaphragm. 

The  so-called  capillaries  of  the  liver  are  really  sinusoids  (see  p. 
222);  they  are  in  direct  contact  with  the  liver-cells,  and  are  not 
surrounded  with  lymph  spaces  as  in  other  secreting  glands;  their 
endothelial  covering  is  in  many  places  incomplete,  and  its  cells  are 
irregularly  branched  and  more  or  less  isolated  from  their  neighbours. 
They  are  called  the  stellate  cells  of  Kupffer.  The  result  is  that  the 
blood  comes  into  direct  contact  with  the  liver-cells. 

The  hepatic  artery,  the  chief  function  of  which  is  to  distribute 
blood  for  nutrition  to  Glisson's  capsule,  the  walls  of  the  ducts  and 
blood-vessels,  and  other  parts  of  the  liver,  is  distributed  in  a  very 


FIG.  362. — Longitudinal  section  of  a  portal  canal,  con- 
taining a  portal  vein,  hepatic  artery  and  hepatic 
duct,  from  the  pig.  P,  Branch  of  vena  portse, 
situated  in  a  portal  canal  amongst  the  lobules  of 
the  liver;  I,  I,  and  giving  off  interlobular  veins; 
there  are  also  seen  within  the  large  portal  vein 
numerous  orifices  of  interlobular  veins  arising 
directly  from  it ;  a,  hepatic  artery ;  d,  bile  duct, 
x  5.  (Kiernan.) 


CH.  XXXV.] 


THE  LIVER 


529 


similar  manner  to  the  portal  vein,  its  blood  being  returned  by  small 

P  p  h 


FIG.  363. — Capillary  network  of  the  lobules  of  the  rabbit's  liver.  The  figure  is  taken  from  a  very 
successful  injection  of  the  liver  veins,  made  by  Harting :  it  shows  nearly  the  whole  of  two  lobules, 
and  parts  of  three  others  ;  p,  interlobular  (portal)  branches  running  in  the  interlobular  spaces ;  h, 
intralobular  (hepatic)  veins  occupying  the  centre  of  the  lobules.  The  interlobular  and  intralobular 
vessels  are  connected  by  radiating  capillaries,  x  45.  (Kolliker.) 

branches  which  pass  into  the  capillary  plexus  of  the  lobules  which 
connects  the  inter-  and  mtfra-lobular  veins. 

The  hepatic  duct  divides  and  subdivides  in  a  manner  very  like 
that  of  the  portal  vein  and  hepatic  artery, 
the  larger  branches  being  lined  by  columnar, 
and  the   smaller   by   small   polygonal   epi- 
thelium. 

The  bile  capillaries  commence  between 
the  hepatic  cells,  and  are  always  bounded  by 
hepatic  cells  on  all  sides,  and  are  thus 
separated  from  the  nearest  blood  capillary 
by  at  least  the  breadth  of  one  cell  (fig.  364). 

To  demonstrate  the  m^r-cellular  net- 
work of  bile  capillaries,  Chrzonszezewsky 
employed  a  method  of  natural  injection. 
A  saturated  aqueous  solution  of  sulph- 
indigotate  of  soda  is  introduced  into  the 
circulation  of  dogs  and  pigs  by  the  jugular 
vein.  The  animals  are  killed  an  hour  and 
a  half  afterwards,  and  the  blood-vessels 
washed  free  from  blood,  or  injected  with 
gelatin  stained  with  carmine.  The  bile- 
ducts  are  then  seen  filled  with  blue,  and 
the  blood-vessels  with  red  material.  If  the  animals  are  killed  sooner 
than  this,  the  indigo  pigment  is  found  within  the  hepatic  cells,  thus 
demonstrating  it  was  through  their  agency  that  the  canals  were  filled. 

2  L 


FIG.  364.— Portion  of  a  lobule  of 
liver,  a,  Bile  capillaries  be- 
tween liver-cells;  b,  blood 
capillaries,  x  350.  (Klein 
and  Noble  Smith.) 


530 


THE   LIVER 


[CH.  XXXV. 


Pfliiger  and  Kupffer  later  discovered  that  the  relation  between 
the  hepatic  cells  and  the  bile  canaliculi  is  even  more  intimate, 
for  they  demonstrated  the  existence  of  vacuoles  in  the  cells  com- 
municating by  minute  intra -cellular  channels  with  the  adjoining  bile 
canaliculi  (fig.  365). 

/7i£m-cellular  canaliculi  in  the  liver-cells  are  not  unique.  Eecent 
research  by  Golgi's  method  has  shown  that  in  the  salivary  and 
gastric  glands,  and  in  the  pancreas,  there  is  a  similar  condition. 


FIG.  365.— Sketches  illustrating  the  mode  of  commencement  of  the  bile  canaliculi  within  the  liver- 
cells  (Heidenhain,  after  Kupffer).  A,  rabbit's  liver,  injected  from  hepatic  duct  with  Berlin  blue. 
The  inter-cellular  canaliculi  give  off  minute  twigs  which  penetrate  into  the  liver-cells,  and  there 
terminate  in  vacuole-like  enlargements.  B,  frog's  liver  naturally  injected  with  sulph-indigotate  of 
soda.  A  similar  appearance  is  obtained,  but  the  iutra-cellular  canaliculi  are  ramified. 

Schafer  has  further  demonstrated  that  the  liver-cells  contain  not 
only  the  intracellular  bile  canaliculi,  but  also  intracellular  blood  canali- 
culi passing  into  the  cells  from  the  capillaries  between  them.  These 
are  too  minute  to  admit  blood-corpuscles.  The  liver-cells  take  certain 
materials  from  the  plasma  and  elaborate  the  constituents  of  the  bile, 
the  bile-salts,  and  the  bile  pigments.  There  can  be  no  doubt  that 
these  substances  are  formed  by  the  hepatic  cells,  for  they  are  not 
found  in  the  blood  nor  in  any  other  organ  or  tissue ;  and  after  extirpa- 
tion of  the  liver  they  do  not  accumulate  in  the  blood.  We  thus  see 
that  in  the  liver,  lymph  does  not  act  as  a  middleman,  as  it  does  in 
the  formation  of  other  secretions. 

The  functions  of  the  liver  are  connected  with  the  general  metab- 
olism of  the  body,  especially  in  connection  with  the  metabolism  of 
carbohydrates  (glycogenic  function)  and  of  fats;  its  relationship  to 
the  metabolism  of  nitrogenous  material  (formation  of  urea,  uric 
acid,  etc.),  we  shall  discuss  with  the  urine.  Another  function  is  the 
formation  of  bile,  which  it  will  be  convenient  to  take  first. 


CH.  XXXV.]  BILE  531 

Bile. 

Bile  is  the  secretion  of  the  liver  which  is  poured  into  the  duo- 
denum :  it  has  been  collected  in  living  animals  by  means  of  a  biliary 
fistula ;  the  same  operation  has  occasionally  been  performed  in  human 
beings.  After  death  the  gall-bladder  yields  a  good  supply  of  bile 
which  is  more  concentrated  than  that  obtained  from  a  fistula. 

Bile  is  being  continuously  poured  into  the  intestine,  but  there 
is  an  increased  discharge  soon  after  the  arrival  of  food  in  the 
duodenum. 

Though  the  chief  blood  supply  of  the  liver  is  by  a  vein  (the 
portal  vein),  the  amount  of  blood  in  the  liver  varies  with  its  needs, 
being  increased  during  the  periods  of  digestion.  This  is  due  to  the 
fact  that  in  the  area  from  which  the  portal  vein  collects  blood — 
stomach,  intestine,  spleen,  and  pancreas  —  the  arterioles  are  all 
dilated,  and  the  capillaries  are  thus  gorged  with  blood.  The 
peristalsis  of  the  intestine  and  the  pumping  action  of  the  spleen 
are  additional  factors  in  driving  the  blood  onwards  to  the  liver. 

The  bile  is  secreted  from  the  portal  blood  at  much  lower  pressure 
than  one  finds  in  glands  such  as  the  salivary  glands,  the  blood  supply 
of  which  is  arterial.  Herring  and  Simpson,  in  experiments  performed 
upon  numerous  animals,  found  that  the  bile  pressure  averages 
30  mm.  of  mercury,  which  is  about  three  times  the  pressure  in 
the  portal  vein.  This  fact  illustrates  the  general  truth  that  secretory 
cells  exercise  pressure. 

Nothing  is  known  of  any  nervous  agency  which  regulates  the 
flow  of  bile ;  the  stimulus  appears  to  be  of  a  chemical  nature,  and 
the  increased  flow  which  occurs  soon  after  the  arrival  of  the  chyme 
in  the  intestine  is  chiefly  due  to  the  action  of  secretin,  for  this 
material  stimulates  the  liver  as  well  as  the  pancreas. 

The  chemical  process  by  which  the  constituents  of  the  bile  are 
formed  is  obscure.  We,  however,  know  that  the  biliary  pigment  is 
produced  by  the  decomposition  of  haemoglobin.  Bilirubin  is,  in  fact, 
identical  with  the  iron-free  derivative  of  haemoglobin  called  haema- 
toidin,  which  is  found  in  the  form  of  crystals  in  old  blood-clots  such 
as  occur  in  the  brain  after  cerebral  haemorrhage  (see  p.  464). 

An  injection  of  haemoglobin  into  the  portal  vein  or  of  substances 
such  as  water  which  liberate  haemoglobin  from  the  red  blood-corpuscles 
produces  an  increase  of  bile  pigment.  If  the  spleen  takes  any  part 
in  the  elaboration  of  bile  pigment,  it  does  not  proceed  so  far  as  to 
liberate  haemoglobin  from  the  corpuscles.  No  free  haemoglobin  is 
discoverable  in  the  blood  plasma  in  the  splenic  vein. 

The  amount  of  bile  secreted  is  differently  estimated  by  different 
observers ;  the  amount  secreted  daily  in  man  varies  from  500  c.c.  to 
a  litre  (1000  c.c.). 


532 


THE  UVEK 


[CH.  XXXV. 


The  constituents  of  the  bile  are  the  bile  salts  proper  (tauro- 
cholate  and  glycocholate  of  soda),  the  bile  pigments  (bilirubin, 
biliverdin),  a  mucinoid  substance,  small  quantities  of  fats,  soaps, 
cholesterin,  lecithin,  urea,  and  mineral  salts,  of  which  sodium 
chloride  and  phosphates  of  calcium  and  iron  are  the  most  important. 

Bile  is  a  yellowish,  reddish-brown,  or  green  fluid,  according  to  the 
relative  preponderance  of  its  two  chief  pigments.  It  has  a  musk-lik@ 
odour,  a  bitter-sweet  taste,  and  an  alkaline  reaction. 

The  specific  gravity  of  human  bile  from  the  gall-bladder  is  1026 
to  1032;  that  from  a  fistula,  1010  to  1011.  The  greater  concentra- 
tion of  gall-bladder  bile  is  partly  explained  by  the  addition  to  it 
from  the  walls  of  that  cavity  of  the  mucinoid  material  it  secretes. 

The  amount  of  solids  in  gall-bladder  bile  is  from  9  to  14  per 
cent.,  in  fistula  bile  from  1/5  to  3  per  cent.  The  following  table  shows 
that  this  low  percentage  of  solids  is  almost  entirely  due  to  want  of  bile 
salts.  This  can  be  accounted  for  in  the  way  first  suggested  by  Schiff 
—that  there  is  normally  a  bile  circulation  going  on  in  the  body,  a 
large  quantity  of  the  bile  salts  that  pass  into  the  intestine  being  first 
split  up,  then  reabsorbed  and  again  secreted.  Such  a  circulation 
would  obviously  be  impossible  in  cases  where  all  the  bile  is  dis- 
charged to  the  exterior. 

The  following  table  gives  some  analyses  of  human  bile : — 


Constituents. 

Fistula  bile 
(healthy  woman. 
Copeman  and 
Winston). 

Fistula  bile  (case 
of  cancer.     Yeo 
and  Herroun). 

Normal  bile 
(Frerichs). 

Sodium  glycocholate 
Sodium  taurocholate 

}        0-6280     | 

0-165 
0*055 

|        9-14 

Cholesterin,  lecithin,  fat  . 
Mucinoid  material    . 
Pigment  .... 

0-0990 
0-1725 
0-0725 

0-038 
|         0-148 

1-18 
2-98 

Inorganic  salts 

0-4510 

0-878 

0-78 

Total  solids       . 
Water  (by  difference) 

1-4230 
98-5570 

1-284 
98-716 

14-08 
85-92 

Bile  Mucin. — There  has  been  considerable  diversity  of  opinion 
as  to  whether  bile  mucin  is  really  mucin.  The  most  recent  work  in 
Hammarsten's  laboratory  shows  that  differences  occur  in  different 
animals.  Thus  in  the  ox  there  is  very  little  true  mucin,  but  a  great 
amount  of  nucleo-protein ;  in  human  bile,  on  the  other  hand,  there 
is  very  little  if  any  nucleo-protein;  the  mucinoid  material  present 
there  is  really  mucin. 

The  Bile  Salts. — The  bile  contains  the  sodium  salts  of  complex 


CH.  XXXV.]  BILE   SALTS   AND   PIGMENTS  533 

amino-acids  called  the  bile  acids.  The  two  acids  most  frequently 
found  are  glycocholic  and  taurocholic  acids.  The  former  is  the  more 
abundant  in  the  bile  of  man  and  herbivora ;  the  latter  in  carnivorous 
animals,  such  as  the  dog.  An  important  difference  between  the  two  is 
that  taurocholic  acid  contains  sulphur,  and  glycocholic  acid  does  not. 
Glycocholic  acid  (C26H43N06)  is  by  the  action  of  dilute  acids  and 
alkalis,  and  also  in  the  intestine,  hydrolysed  and  split  into  glycine  or 
amino-acetic  acid  and  cholalic  acid. 

C26H43N06   +    H20   -   CH2.NH2.COOH   +   C24H40O5. 

[Glycocholic  acid.]  [Glycine.]  [Cholalic  acid.] 

The  glycocholate  of  soda  has  the  formula  C26H42NaN06. 
Taurocholic  acid  (C20H45N07S)  similarly  splits  into  taurine  or 
amino-isethionic  acid  and  cholalic  acid. 

C26H45N07S   +    H20   =   (CH2),.NH2.S02.OH    +   C24H40O6 

[Taurocholic  acid.]  [Taurine.]  [Cholalic  acid.] 

The  taurocholate  of  soda  has  the  formula  C26H44NaN07S. 

The  colour  reaction  called  Pettenkofer's  reaction  is  due  to  the 
presence  of  cholalic  acid.  Small  quantities  of  cane  sugar  and  strong 
sulphuric  acid  are  added  to  the  bile.  The  sulphuric  acid  acting  on 
sugar  forms  a  small  quantity  of  a  substance  called  furfuraldehyde,  in 
addition  to  other  products.  The  furfuraldehyde  gives  a  brilliant 
purple  colour  with  cholalic  acid. 

The  Bile  Pigments. — The  two  chief  bile  pigments  are  bilirubin 
and  biliverdin.  Bile  which  contains  chiefly  the  former  (such  as  dog's 
bile)  is  of  a  golden  or  orange-yellow  colour,  while  the  bile  of  many 
herbivora,  which  contains  chiefly  biliverdin,  is  either  green  or  bluish- 
green.  Human  bile  is  generally  described  as  containing  chiefly 
bilirubin ;  but  this  is  by  no  means  always  so.  The  bile  pigments 
show  no  absorption  bands  with  the  spectroscope. 

Bilirubin  has  the  formula  C32H36N406:  it  is  thus  an  iron-free 
derivative  of  haemoglobin.  The  iron  is  apparently  stored  up  in  the 
liver  cells,  perhaps  for  future  use  in  the  manufacture  of  new  haemo- 
globin. The  bile  contains  only  a  trace  of  iron. 

Biliverdin  has  the  formula  (C16H18K204)^;  the  value  of  x 
is  uncertain:  it  may  occur  as  such  in  bile;  it  may  be  formed  by 
simply  exposing  red  bile  to  the  oxidising  action  of  the  atmosphere ; 
or  it  may  be  formed  as  in  Gmelin's  test  by  the  more  vigorous 
oxidation  produced  by  fuming  nitric  acid. 

Gmelin's  test  consists  in  a  play  of  colours — green,  blue,  red,  and 
finally  yellow,  produced  by  the  oxidising  action  of  fuming  nitric  acid 
(that  is,  nitric  acid  containing  nitrous  acid  in  solution).  The  end  or 
yellow  product  is  called  choletelin,  C3.2H3CN4012. 

Hydrobilirubin. — If  a  solution  of  bilirubin  or  biliverdin  in  dilute 


534  THE  LIVES  [CIL  XXXV. 

alkali  is  treated  with  sodium  amalgam  or  allowed  to  putrefy,  a 
brownish  pigment,  which  is  a  reduction  product,  is  formed  called 
hydrobilirubin,  C32H40]Sr407.  It  shows  a  dark  absorption  band 
between  I  and  F,  and  a  fainter  band  in  the  region  of  the  D  line. 

This  substance  is  interesting  because  a  similar  substance  is  formed 
from  the  bile  pigment  by  reduction  processes  in  the  intestine,  and 
constitutes  stercobilin,  the  pigment  of  the  faeces.  Some  of  this  is 
absorbed  and  ultimately  leaves  the  body  in  the  urine  as  one  of  its 
pigments  called  urobilin.  A  small  quantity  of  urobilin  is  sometimes 
found  preformed  in  the  bile.  The  identity  of  urobilin  and  stercobilin 
has  been  frequently  disputed,  but  the  recent  work  of  Garrod  and 
Hopkins  has  confirmed  the  old  statement  that  they  are  the  same 
substance  with  different  names.  Hydrobilirubin  differs  from  urobilin 
in  containing  more  nitrogen  (9*2  instead  of  4*1  per  cent.). 

Cholesterin. — Small  quantities  of  this  substance  are  found  in 
normal  bile.  It  may  occur  in  excess,  and  form  the  concretions 
known  as  gall-stones,  which  are  usually  more  or  less  tinged  with 
bilirubin.  Its  properties  and  reactions  are  described  on  p.  435. 

The  Uses  of  Bile. — Bile  is  doubtless,  to  a  certain  extent, 
excretory.  Some  state  that  it  has  a  slight  action  on  fats  and  carbo- 
hydrates, but  its  principal  action  is  as  a  coadjutor  to  the  pancreatic 
juice  (especially  in  the  digestion  of  fat).  In  some  animals  it  has  a 
feeble  diastatic  power. 

Bile  is  said  to  be  a  natural  antiseptic,  lessening  the  putrefactive 
processes  in  the  intestine.  This  is  very  doubtful.  Though  the  bile 
salts  are  weak  antiseptics,  the  bile  itself  is  readily  putrescible,  and 
the  power  it  has  of  diminishing  putrescence  in  the  intestine  is  due 
chiefly  to  the  fact  that  by  increasing  absorption  it  lessens  the  amount 
of  putrescible  matter  in  the  bowel. 

When  the  bile  meets  the  chyme  the  turbidity  of  the  latter  is 
increased  owing  to  the  precipitation  of  unpeptonised  protein.  This 
is  an  action  due  to  the  bile  salts,  and  it  has  been  surmised  that  this 
conversion  of  the  chyme  into  a  more  viscid  mass  is  to  hinder  some- 
what its  progress  through  the  intestines ;  it  clings  to  the  intestinal  wall, 
thus  allowing  absorption  to  take  place.  Bile  stimulates  peristalsis 
in  the  large  intestine. 

Bile  is  alkaline;  it  therefore  assists  the  pancreatic  juice  in 
neutralising  the  chyme  that  leaves  the  stomach.  It  assists  the 
absorption  of  fats  (see  p.  548).  It  is  also  a  solvent  of  fatty  acids. 

We  have  seen  that  fistula  bile  is  poor  in  solids  as  compared  with 
normal  bile,  and  that  this  is  explained  on  the  supposition  that  the 
normal  bile  circulation  is  not  occurring — the  liver  cannot  excrete 
what  it  does  not  receive  back  from  the  intestine.  Schiff  was  the  first 
to  show  that  if  the  bile  is  led  back  into  the  duodenum,  or  even  if  the 
animal  is  fed  on  bile,  the  percentage  of  solids  in  the  bile  excreted  is 


CH.  XXXV.]  THE   BILE   CIRCULATION  535 

at  once  raised.  It  is  on  these  experiments  that  the  theory  of  a  bile 
circulation  is  mainly  founded.  The  bile  circulation  relates,  however, 
chiefly,  if  not  entirely,  to  the  bile  salts :  they  are  found  but  sparingly 
in  the  faeces ;  they  are  only  represented  to  a  slight  extent  in  the  urine : 
hence  it  is  calculated  that  seven-eighths  of  them  are  reabsorbed  from 
the  intestine.  Small  quantities  of  cholalic  acid,  taurine,  and  glycine 
are  found  in  the  faeces;  the  greater  part  of  these  products  of  the 
decomposition  of  the  bile  salts  is  taken  by  the  portal  vein  to  the 
liver,  where  they  are  once  more  synthesised  into  the  bile  salts.  Some 
of  the  taurine  is  absorbed  and  excreted  as  tauro-carbamic  acid  in  the 
urine.  Some  of  the  absorbed  glycine  may  be  excreted  as  urea.  The 
pigment  is  changed  into  stercobilin  and  leaves  the  body  partly  in 
the  faeces,  but  some  is  absorbed  and  is  finally  excreted  as  urobilin 
in  the  urine.  The  cholesterin  in  the  faeces  was  formerly  supposed 
to  be  a  bile-residue;  but  in  some  animals,  especially  those  which 
feed  on  grass,  the  source  of  the  faecal  cholesterin  is  the  phytosterin 
(vegetable  cholesterin)  in  the  food.  In  some  cases  it  is  reduced  and 
forms  a  derivative  termed  coprosterin  (Austin  Flint's  stercorin). 

The  bile-expelling  mechanism  must  be  carefully  distinguished 
from  the  bile-secreting  action  of  the  liver-cells.  The  bile  is  forced 
into  the  ducts,  and  ultimately  into  the  duodenum,  by  the  pressure  of 
newly-formed  bile  pressing  on  that  previously  in  the  ducts,  and  this 
is  assisted  by  the  contraction  of  the  plain  muscular  fibres  of  the 
larger  ducts  and  gall-bladder,  which  occurs  when  the  food  enters  the 
duodenum.  In  cases  of  obstruction,  as  by  a  gall-stone,  in  the  ducts, 
this  action  becomes  excessive,  and  gives  rise  to  the  intense  pain 
known  as  hepatic  colic. 

Many  cholagogues  (bile-drivers),  such  as  calomel,  act  on  the  bile- 
expelling  mechanism  and  increase  the  peristalsis  of  the  muscular 
tissue ;  they  do  not  really  cause  an  increased  formation  of  bile. 

Jaundice. — The  commonest  form  of  jaundice  is  produced  by 
obstruction  in  the  bile-ducts  preventing  the  bile  entering  the 
intestine.  A  very  small  amount  of  obstruction,  for  instance,  a 
plug  of  mucus  produced  in  excess  owing  to  inflammatory  processes, 
will  often  be  sufficient,  as  the  bile  is  secreted  at  comparatively  low 
pressure.  Under  these  circumstances,  the  faeces  are  whitish  or  clay 
coloured,  and  the  bile  passing  backwards  into  the  lymph,*  enters 
the  blood  and  is  thus  distributed  over  the  body,  causing  a  yellow 
tint  in  the  skin  and  mucous  membranes,  and  colouring  the  urine. 

In  some  cases  of  jaundice,  however  (e.g.,  produced  by  various 
poisons),  there  is  no  obvious  obstruction;  the  causes  of  non- 
obstructive,  or  blood-jaundice,  form  a  pathological  problem  of  some 
interest.  Some  years  ago  it  was  believed  that  the  bile  pigment  was 

*  The  absorption  is  by  the  lymph,  because  if  jaundice  is  produced  in  an 
animal  by  ligature  of  the  bile  duct,  it  will  cease  when  the  thoracic  duct  is  tied, 


536  THE  LIYEK  [CH.  XXXV. 

actually  produced  in  the  blood.  But  all  recent  work  shows  that  the 
liver  is  the  only  place  where  production  of  bile  occurs,  and  that  in  all 
cases  of  so-called  non-obstructive  jaundice,  the  bile  is  absorbed  from 
the  liver.  There  may  be  obstruction  present  in  the  smaller  ducts,  or 
the  functions  of  the  liver  may  be  so  upset  that  the  bile  passes  into 
the  lymph  even  when  there  is  no  obstruction. 

The  Glycogenic  Function  of  the  Liver. 

The  important  fact  that  the  liver  normally  forms  sugar,  or  a 
substance  readily  convertible  into  it,  was  discovered  by  Claude 
Bernard  in  the  following  way:  He  fed  a  dog  for  seven  days  with  food 
containing  a  large  quantity  of  sugar  and  starch;  and,  as  might  be 
expected,  found  sugar  in  both  the  portal  and  hepatic  blood.  But 
when  this  dog  was  fed  with  meat  only,  to  his  surprise,  sugar  was  still 
found  in  the  blood  of  the  hepatic  veins.  Eepeated  experiments  gave 
invariably  the  same  result ;  no  sugar  was  found,  under  a  meat  diet, 
in  the  portal  vein,  if  care  were  taken,  by  applying  a  ligature  on  it  at 
the  transverse  fissure,  to  prevent  reflux  of  blood  from  the  hepatic 
venous  system.  Bernard  found  sugar  also  in  the  substance  of  the 
liver.  It  thus  seemed  certain  that  the  liver  formed  sugar,  even  when, 
from  the  absence  of  carbohydrates  in  the  food,  none  could  have  been 
brought  directly  to  it  from  the  stomach  or  intestines. 

Bernard  found,  subsequently,  that  a  liver,  removed  from  the 
body,  and  from  which  all  sugar  had  been  completely  washed  away  by 
injecting  a  stream  of  water  through  its  blood-vessels,  contained  sugar 
in  abundance  after  the  lapse  of  a  few  hours.  This  post-mortem  pro- 
duction of  sugar  was  a  fact  which  could  only  be  explained  on  the 
supposition  that  the  liver  contained  a  substance  readily  convertible 
into  sugar;  and  this  theory  was  proved  to  be  correct  by  the  dis- 
covery of  a  substance  in  the  liver  allied  to  starch,  and  now  termed 
glycogen  or  animal  starc'h.  We  are  thus  led  to  the  conclusion  that 
glycogen  is  formed  first  and  stored  in  the  liver  cells,  and  that  the 
sugar,  when  present,  is  the  result  of  its  transformation. 

Source  of  G-lycogen. — Although  the  greatest  amount  of  glycogen 
is  produced  by  the  liver  upon  a  diet  of  starch  or  sugar,  a  certain 
quantity  is  produced  upon  a  protein  diet.  It  must,  then,  be  produced 
by  protoplasmic  activity  within  the  cells.  The  glycogen  when  stored 
in  the  liver  cells  may  readily  be  demonstrated  in  sections  of  liver 
containing  it  by  its  reaction  (red  colour)  with  iodine,  and  moreover, 
when  the  hardened  sections  are  soaked  in  water  to  dissolve  out 
the  glycogen,  the  protoplasm  of  the  cell  may  be  so  vacuolated  as  to 
appear  little  more  than  a  framework.  In  the  liver  of  a  hibernating 
frog  the  amount  of  glycogen  stored  up  in  the  liver  cells  is  very 
considerable. 


CH.  XXXV.]  GLYCOGBNIC   FUNCTION  537 

Average  Amount  of  Glycogen  in  the  Liver  of  Dogs  under  various  Diets  (Pavy). 

Amount  of 
Diet.  Glycogen  in  Liver. 

Animal  food 7 '19  per  cent. 

Animal  food  with  sugar  (about  |-lb.  of  sugar  daily)    .     14*5          ,, 
Vegetable  diet  (potatoes,  with  bread  or  barley-meal)  .     17 -23        „ 

The  dependence  of  the  formation  of  glycogen  on  the  kind  of  food 
taken  is  also  well  shown  by  the  following  results,  obtained  by  the 
same  experimenter : — 

Average  Quantity  of  Glycogen  found  in  the  Liver  of  Rabbits  after  Fasting,  and 
after  a  Diet  of  Starch  and  Sugar  respectively. 

Average  amount  of 
Glycogen  in  Liver. 

After  fasting  for  three  days Practically  absent. 

„     diet  of  starch  and  grape-sugar      .        .        .     15 '4  per  cent. 
„          „      cane  sugar 16'9        „ 

The  diet  most  favourable  to  the  production  of  a  large  amount  of 
glycogen  is  a  mixed  diet  containing  a  large  amount  of  carbohydrate, 
but  with  some  protein.  It  is  also  possible  that  fats  may  form  a 
source  of  glycogen,  in  virtue  of  the  glycerin  they  contain. 

Destination  of  Glycogen. — There  are  two  chief  theories  as  to  the 
destination  of  the  hepatic  glycogen.  (1)  That  the  glycogen  is  con- 
verted into  sugar  during  life  by  the  agency  of  an  enzyme  (liver 
diastase  or  glycogenase)  found  in  the  liver;  and  that  the  sugar  is 
conveyed  away  by  the  blood  of  the  hepatic  veins,  to  undergo  com- 
bustion in  the  tissues.  (2)  That  the  conversion  into  sugar  only  occurs 
after  death,  and  that  during  life  glycogen  is  transformed  into  fat. 

The  first  view  is  that  of  Claude  Bernard,  and  has  been  adopted  by 
the  majority  of  physiologists.  The  second  view  is  that  of  Pavy: 
he  denies  that  the  liver  is  a  sugar-forming  organ,  he  regards  it  as  a 
sugar-destroying  organ;  the  sugar  is  stored  as  animal  starch,  but 
never  again  leaves  the  liver  as  sugar  during  life.  He  has  been  unable 
to  find  more  sugar  in  the  hepatic  blood  than  in  the  portal  blood. 
Other  observers  have  found  an  increase  in  the  sugar  of  the  blood 
leaving  the  liver,  but  the  accurate  estimation  of  sugar  in  a  fluid  rich 
in  proteins  is  a  matter  of  great  difficulty.  Even  if  the  increase  is  so 
small  as  hardly  to  be  detected,  it  must  be  remembered  that  the 
whole  blood  of  the  body  passes  through  the  liver  about  once  a 
minute,  so  that  a  very  small  increase  each  time  would  mount  up  to 
a  large  total. 

Pavy  further  denies  that  the  post-mortem  formation  of  sugar  from 
glycogen  that  occurs  in  an  excised  liver  is  a  true  picture  of  what 
occurs  during  life,  but  is  due  to  an  enzyme  which  is  only  formed  after 
death.  During  life,  he  regards  the  glycogen  as  a  source  of  other  sub- 
stances, such  as  fat  and  protein.  It  is  certainly  a  fact  that  increase 


538  THE  LIVER  [en.  xxxv. 

of  carbohydrate  food  leads  to  the  formation  of  fat  in  the  body  and  in 
the  liver-cells.  In  support  of  the  theory  that  glycogen  may  also  con- 
tribute to  the  formation  of  proteins,  he  has  shown  that  many  proteins 
contain  a  carbohydrate  radical. 

The  prevalent  opinion  is  that  the  liver-cells  may  be  able  to  con- 
vert part  of  the  store  of  glycogen  into  fat ;  part  also  of  the  sugar 
formed  from  glycogen  may  unite  with  protein  to  form  a  gluco- 
protein;  but  most  of  the  glycogen  leaves  the  liver  as  sugar 
(dextrose),  so  justifying  the  name  (literally,  mother-substance  of 
sugar)  given  to  it  by  Bernard. 

Diabetes. — In  certain  disorders  of  metabolism,  excess  of  sugar 
occurs  in  the  blood,  and  leaves  the  body  by  the  urine  (glycosurid). 
Under  normal  circumstances,  the  transformation  of  the  hepatic 
glycogen  into  sugar  is  a  sufficiently  slow  process  to  keep  the  sugar 
in  the  blood  at  such  a  low  percentage  that  glycosuria  does  not  occur. 
Glycosuria  takes  place  when  the  transformation  of  glycogen  into 
sugar  is  excessive,  as  in  puncture  diabetes,  described  below. 

"Alimentary  glycosuria"  is  usually  a  temporary  condition,  in 
which  either  the  diet  contains  too  much  carbohydrate  for  the  liver  to 
store  as  glycogen,  or  else  the  liver  is  comparatively  inactive  and 
incapable  of  dealing  with  the  usual  carbohydrate  supply.  This  state 
of  things  may  be  remedied  by  reducing  the  amount  of  carbohydrate 
ingested,  or  by  improving  the  condition  of  the  liver.  The  normal 
"  assimilation  limit "  for  dextrose  in  man  given  in  one  dose  by  the 
mouth  is  about  200  grammes. 

We  must,  however,  remember  that  sugar  is  not  poured  into  the 
blood  to  accumulate  there,  but  is  removed  by  the  muscular  and  other 
tissues  which  the  blood  traverses,  and  is  there  burnt  to  serve  as  a 
source  of  energy ;  if  the  tissues  are  unable  to  utilise  the  sugar  in 
this  way,  it  accumulates  in  the  blood  and  overflows  into  the  urine ; 
this  is  the  usual  condition  in  the  disease  called  diabetes  mellitus  in 
man;  and  a  similar  condition  may  be  produced  in  animals  by 
removal  of  the  pancreas.  Many  cases  of  diabetes  mellitus  in  man 
are  due  to  disease  of  the  pancreas.  In  many  cases  the  diabetic 
condition  may  be  removed  by  rigid  abstention  from  starchy  and 
saccharine  food.  In  other  cases  diet  makes  little  or  no  difference; 
in  this  condition  the  sugar  must  come  from  the  metabolism  of  the 
protein  constituents  of  protoplasm ;  40  per  cent,  or  more  of  the  kata- 
bolised  protein  may  leave  the  body  as  sugar,  certain  of  its  cleavage 
products  (for  instance,  alanine,  see  p.  615)  acting  as  intermediate 
substances  in  sugar  formation.  This  serious  condition  is  analogous  to 
what  can  be  produced  artificially  by  the  poison  known  as  phloridzin, 
and  is  possibly  produced  in  man  by  some  poison  acting  in  a  similar  way. 

The  principal  ways  in  which  diabetes  may  be  produced  are : — 

(1)  By  diabetic  puncture. — Claude  Bernard  was  the  first  to  show 


CH.  XXXV.]  DIABETES  539 

that  injury  to  the  floor  of  the  fourth  ventricle  in  the  region  of  the  vaso- 
motor  centre  leads  to  glycosuria.  In  man,  also,  disease  of  the  bulb  is 
frequently  associated  with  glycosuria.  These  observations  led  to  the 
erroneous  conclusion  that  diabetes  is  always  of  nervous  origin.  The 
diabetes  produced  in  this  way  cannot  be  the  result  of  vaso-motor 
disturbances,  but  is  due  to  an  influence  on  the  glycogenolytic  nervous 
mechanism  (see  p.  541),  and  the  glycosuria  only  occurs  when  the 
liver  has  within  it  a  store  of  glycogen. 

(2)  By  extirpation  of  the  pancreas. — Minkowski  and  v.  Mering 
in  1889  showed,  that  complete  extirpation  of  the  pancreas  produces 
in  animals  a  diabetic  condition,  even  if  no  carbohydrate  food  is 
contained  in  the  diet.  The  disease  terminates  fatally  within  a  few 
weeks.  If  the  removal  is  not  complete,  the  intensity  of  the  glyco- 
suria depends  upon  the  amount  of  pancreatic  tissue  left  behind. 
One-fourth  to  a  fifth  of  the  gland  is  usually  sufficient  to  prevent  the 
occurrence  of  the  diabetic  state.  It  does  not  depend  on  the  connec- 
tion of  the  pancreas  with  the  intestine,  and  this  proves  that  the 
suppression  of  pancreatic  juice  is  not  the  cause  of  the  diabetes.  The 
same  conclusion  was  reached  in  other  experiments  in  which  the 
gland  ducts  were  occluded  by  paraffin  wax ;  no  glycosuria  resulted. 
Moreover,  the  effect  of  pancreatic  extirpation,  so  far  as  diabetes  is 
concerned,  can  be  prevented  by  grafting  a  portion  of  the  pancreas 
into  the  abdominal  wall,  or  even  under  the  skin.  It  is  therefore 
believed  that  the  pancreas  forms  an  internal  secretion,  in  addition  to 
its  external  secretion  or  pancreatic  juice.  The  former  passes  into 
the  blood  and  plays  an  essential  part  in  carbohydrate  metabolism. 

The  islets  of  Langerhans  have  by  many  been  held  responsible  for 
this  portion  of  the  duties  of  the  pancreas.  The  evidence  in  favour  of 
this  view  is  that  in  human  diabetes  the  islets  are  frequently 
degenerated,  atrophied,  or  even  absent ;  in  animals,  ligature  of  the 
pancreatic  ducts  leads  to  atrophy  of  the  pancreatic  acini,  but  not  of 
the  islets,  and  under  those  conditions  no  glycosuria  occurs. 

This  view  may  be  accepted  with  considerable  confidence,  for  the 
observations  of  certain  investigators  that  the  islets  merely  represent 
a  stage  in  the  development  of  the  ordinary  acini,  have  been 
disproved  or  at  any  rate  discredited. 

We  have  seen  that  in  diabetes,  the  power  of  the  tissue  cells  to 
burn  sugar  is  lessened;  nevertheless,  other  diseases  in  which 
diminished  oxidation  occurs  are  not  necessarily  accompanied  with 
glycosuria.  The  difficulty  in  diabetes  probably  lies  in  an  impair- 
ment of  the  capacity  of  the  cells  of  the  body  to  prepare  the  sugar 
for  oxidation.  In  this  process  the  sugar  or  its  derivative  glycuronic 
acid  is  split  into  smaller  molecules,  and  ultimately  into  water  and 
carbon  dioxide.  If  two  hydrogen  atoms  in  the  CH2OH  group  of 
dextrose  are  replaced_by  one  of  oxygen,  we  obtain  glycuronic  acid. 


540  THE  LIVER  [CH.  XXXV. 

This  oxidation  is  readily  brought  about  in  the  body,  and  glycuronic 
acid  is  usually  found  in  diabetic  urine  ;  but  the  further  oxidation  into 
water  and  carbon  dioxide  is  a  more  difficult  task,  because  it  involves 
the  disruption  of  the  linkage  of  the  carbon  atoms.  Possibly  it  is 
here  that  the  internal  secretion  of  the  pancreas  comes  in. 

Cohnheim  discovered  that  muscle  by  itself  and  that  an  extract  of 
pancreas  by  itself  have  very  little  effect  in  destroying  sugar  at  body 
temperature;  but  if  a  mixture  is  made  of  surviving  muscle,  pan- 
creatic extract,  and  sugar,  the  last-named  substance  rapidly  dis- 
appears. Several  observers  have  confirmed  this  observation,  but 
others  attribute  it  to  bacterial  action ;  according  to  this  view,  the 
pancreas  forms  a  substance  which  activates  the  glycolytic  (sugar- 
destroying)  enzyme  of  muscular  tissue.  The  activating  substance 
is  not  an  enzyme,  because  the  pancreatic  extract  does  not  lose  this 
property  when  it  is  boiled. 

Levene,  like  others,  finds  that  sugar  disappears  when  mixed  with  muscle  and 
pancreatic  extract,  but  he  does  not  regard  this  as  glycolysis  in  the  usual  accepta- 
tion of  the  word,  namely,  combustion  into  carbonic  acid  and  water.  He  considers 
that  the  sugar  disappears  because  its  molecules  are  condensed  into  a  heavier 
carbohydrate,  and  states  that  the  sugar  can  once  more  be  recovered  from  the 
mixture  after  hydrolysis  with  acid.  If  this  is  confirmed  the  view  above  advanced 
will  need  revision,  and  the  action  of  the  pancreatic  hormone  is  best  explained,  as 
suggested  on  the  next  page,  as  antagonistic  to  that  of  adrenaline.  Of  all  the  tissue 
cells  examined  by  Levene,  the  leucocytes  alone  were  found  to  possess  real 
glycolytic  power,  lactic  acid  being  an  intermediate  stage  before  the  final  products 
(carbonic  acid  and  water)  are  reached. 

(3)  By  administration  of  phloridzin.  —  Many  drugs  produce 
temporary  glycosuria;  some,  such  as  morphine,  may  act  on  the 
diabetic  nerve-centre;  others,  such  as  anaesthetics  and  carbon 
monoxide,  may  upset  the  balance  between  the  blood-gases,  and  thus 
affect  tissue  respiration  and  lead  to  an  accumulation  of  sugar  in  the 
blood.  The  most  potent  poison  in  producing  a  diabetic  state  is, 
however,  phloridzin,  which  is  a  glucoside,  but  the  sugar  passed  in  the 
urine  is  far  too  great  to  be  accounted  for  by  the  small  amount  of 
sugar  derivable  from  the  drug.  Besides  that,  phloretin,  a  derivative 
of  phloridzin,  free  from  sugar,  produces  the  same  results. 

Phloridzin  produces  diabetes  in  starved  animals,  or  in  those  in 
which  any  carbohydrate  store  must  have  been  got  rid  of  by  the 
previous  administration  of  the  same  drug.  Phloridzin-diabetes  is 
therefore  analogous  to  those  intense  forms  of  diabetes  in  man  in  which 
the  sugar  must  be  derived  from  protein  metabolism.  The  increase  in 
protein  metabolism  is  signalised  by  the  rise  in  the  output  of  nitrogen ; 
in  these  cases  the  ratio  of  dextrose  to  nitrogen  in  the  urine  is  3'6  : 1. 
If  such  a  ratio  occurs  in  man  on  a  diet  free  from  carbohydrates,  a 
serious  condition  is  revealed ;  Graham  Lusk  calls  it  the  "  fatal  ratio." 

A  puzzling  feature  is  the  absence  of  an  increase  of  free  sugar  in 


CH.  XXXV.]  THE   LIVER  AND   FAT  METABOLISM  541 

the  blood ;  if  the  phloridzin  is  directly  injected  into  one  renal  artery, 
sugar  rapidly  appears  in  the  secretion  of  that  kidney ;  some  explain 
this  by  supposing  that  the  sugar  is  formed  within  the  kidney  cells 
from  some  substance  in  the  blood,  possibly  protein ;  whereas  others 
consider  that  the  kidney  is  rendered  so  permeable  to  sugar,  that  the 
percentage  in  the  blood  is  kept  at  a  low  figure.  This  view  is  sup- 
ported by  Underbill's  recent  work :  he  has  shown  that  in  dogs  and 
rabbits,  if  the  renal  structures  are  ligatured,  or  the  kidney  injured 
by  sodium  tartrate,  the  secretion  of  urine  ceases,  and  after  the 
administration  of  phloridzin,  the  sugar  in  the  blood  rises  consider- 
ably over  the  normal. 

(4)  By  administration  of  adrenaline. — This  drug  also  produces  a 
diabetic  condition,  but  in  this  case  there  is  excess  of  sugar  in  the 
blood  also.  Recent  research  indicates  that  adrenaline  produces  an 
increased  discharge  of  sugar  from  the  liver,  and  that  under  normal 
conditions  this  is  regulated  by  an  antagonistic  hormone  present 
in  the  internal  secretion  of  the  pancreas. 

Glycogenolytic  Nerves. — The  disappearance  of  glycogen  from 
the  liver  cells  after  the  stimulation  of  the  splanchnic  nerves  can 
be  seen  histologically.  This  is  due  to  a  direct  influence  of  the  nerves 
on  the  liver  cells,  for  the  effect  is  obtained  after  the  circulation  is 
stopped  by  ligature  of  the  aorta  and  portal  vein. 

The  most  complete  work  on  this  subject  is  that  by  J.  J.  R  Macleod, 
who  finds  that  the  glycogenolytic  fibres  (the  action  of  which  is  to 
increase  the  sugar  in  the  blood  at  the  expense  of  the  hepatic  glycogen) 
are  demonstrable  with  certainty  only  in  the  case  of  the  greater 
splanchnic  nerves.  If  it  occurs  as  the  result  of  vagus  stimulation 
(as  Bernard  stated),  it  is  due  to  the  asphyxia  which  is  produced ;  if 
precautions  are  taken  to  prevent  asphyxia,  no  increase  of  the 
blood  sugar  is  found.  In  asphyxia  it  is  increase  of  carbonic  acid, 
and  not  loss  of  oxygen,  which  produces  the  glycosuric  condition,  and 
the  former  gas  probably  acts  directly  on  the  liver  cells  themselves. 

The  Liver  and  Fat  Metabolism. 

The  work  of  Leathes,  Hartley,  and  others  has  shown 
that  the  liver  has  an  important  use  in  the  preparation  of  fats  for 
their  final  disintegration  into  carbonic  acid  and  water.  The  fat 
stored  in  adipose  tissue  must  first  be  transported  into  the  blood- 
stream ;  the  lipase  found  in  connective  tissue  liberates  the  glycerin 
and  fatty  acids,  and  thus  renders  such  transportation  possible.  It 
is  first  taken  to  the  liver,  where  it  can  be  easily  detected,  but  not  in 
other  organs,  and  the  rupture  of  the  long  carbon  chains  of  the  fatty 
acid  begins:  it  is  first  desaturated  and  then  broken  up  into  lower 
fatty  acids  such  as  caproic  and  butyric.  The  unsaturated  products 


542  THE  LIVER  [CH.  XXXV. 

which  are  next  found  in  the  cells  of  other  organs  throughout  the 
body  disintegrate,  probably  where  the  un saturated  links  have  been 
introduced,  and  the  lower  acids  so  formed  by  successive  oxidations 
break  down  to  molecules  of  the  size  of  acetic  acid,  and  are  lastly 
completely  burnt  to  carbonic  acid  and  water. 

Acidosis. — This  condition  is  seen  in  diabetes;  poisonous  acids 
in  the  blood  produce  a  state  of  coma,  or  deep  unconsciousness,  which 
may  finally  cause  death.  For  a  diabetic  is  not  only  unable  to  burn 
and  so  utilise  carbohydrate,  but  he  fails  in  a  similar  way  in  his 
utilisation  of  fat.  Butyric  acid  and  /3-hydroxybutyric  acid  are  prob- 
ably normal  intermediate  products  in  fat  katabolism,  but  a  healthy 
man  on  a  normal  diet  is  able  still  further  to  oxidise  them  into 
carbonic  acid  and  water.  But  on  an  abnormal  diet,  for  instance, 
when  carbohydrate  food  is  absent,  fat-cleavage  largely  stops  short 
at  the  hydroxybutyric  acid  stage;  consequently  this  and  possibly 
other  related  fatty  acids  accumulate  and  cause  acidosis ;  this  condi- 
tion is  increased  the  more  fat  is  given  in  the  food,  and  the  acidosis 
of  diabetes  is  similarly  increased  by  fatty  food.  These  poisonous 
acids  were  once  believed  to  originate  from  proteins;  if  that  weie 
so  there  ought  to  be  an  increase  of  other  protein  katabolites  in 
the  urine,  which  there  is  not.  The  acids  decrease  the  alkalinity  and 
carbonic  acid  of  the  blood,  and  the  ammonia  of  the  urine  is  increased  ; 
this  indicates  an  attempt  of  the  body  to  neutralise  the  acids. 

The  hydroxybutyric  acid  does  not  pass  entirely  unchanged  into 
the  urine.  /3-Hydroxybutyric  acid  is  CH3.  CHOH.  CH2.  COOH. 
By  oxidation,  the  two  hydrogen  atoms  in  thick  type  are  removed 
to  form  water,  and  this  leaves  CH3 .  CO  .  CH2 .  COOH,  which  is  aceto- 
acetic  acid :  when  the  COO  in  thick  type  is  removed  we  get 
acetone  (CH3 .  CO .  CH3),  which  gives  the  breath  and  urine  of  such 
patients  an  apple-like  smell. 

In  these  changes  the  liver  plays  an  important  part  by  means 
of  certain  enzymes  which  Dakin  has  proved  to  exist.  One  enzyme, 
called  fi-hydroxy'butyrase,  is  an  oxidase;  it  oxidises  the  /3-hydroxy- 
butyric  into  aceto-acetic  acid,  and  its  action  is  increased  by  the 
addition  of  blood  or  oxyhaemoglobin,  which  furnishes  the  necessary 
oxygen.  It  probably  is  active  in  health  as  well  as  in  disease,  the 
aceto-acetic  acid  being  finally  burnt  into  carbonic  acid  and  water. 
The  other  enzyme  which  forms  acetone  is  not  an  oxidative  one,  and 
acetone  formation  probably  never  occurs  in  the  healthy  state. 

Pat  Synthesis. — So  much  for  the  relationship  of  the  liver  to  fat 
katabolism;  but  it  appears  that  the  liver  is  also  important  in  the 
building  up  of  fats,  especially  of  those  complex  fats  called  phospha- 
tides.  It  is,  however,  possible  that  this  is  not  exclusively  the  property 
of  liver  cells :  when  once  the  desaturated  acids  are  supplied  by  the 
liver,  each  organ  can  make  its  own  phosphatides  for  itself. 


CHAPTEK  XXXVI 

THE   ABSORPTION    OF   FOOD 

is  digested  in  order  that  it  may  be  absorbed.  It  is  absorbed  in 
order  that  it  may  be  assimilated,  that  is,  become  an  integral  part  of 
the  living  material  of  the  body.  The  digested  food  thus  diminishes 
in  quantity  as  it  passes  along  the  alimentary  canal,  and  the  faeces 
contain  the  undigested  or  indigestible  residue. 

In  the  mouth  and  oesophagus  the  thickness  of  the  epithelium  and 
the  quick  passage  of  the  food  through  these  parts  reduce  absorption 
to  a  minimum.  Absorption  takes  place  very  slightly  in  the  stomach. 
The  most  recent  observations  show  that  water  is  not  absorbed 
in  the  stomach,  but  alcohol  is  absorbed  to  some  extent.  Salts 
also  do  not  seem  to  be  absorbed  unless  present  in  great  concentra- 
tions, such  as  do  not  occur  in  normal  diets ;  sugar  is  absorbed  with 
difficulty.  The  small  intestine,  with  its  folds  and  villi  to  increase  its 
surface,  is  the  great  place  for  absorption.*  Absorption  begins  in  the 
duodenum,  and  the  products  of  digestion  have  largely  disappeared  by 
the  time  the  intestinal  contents  reach  the  ileo-caecal  valve  at  the 
commencement  of  the  large  intestine ;  in  the  large  intestine,  absorp- 
tion (mainly  of  water)  occurs  also,  but  to  a  less  extent. 

Foods  such  as  water  and  soluble  salts  like  sodium  chloride  are 
absorbed  unchanged.  The  organic  foods  are,  however,  considerably 
changed,  colloid  materials  such  as  starch  and  protein  being  converted 
respectively  into  the  diffusible  materials  sugar  and  ammo-acids. 

There  are  two  channels  of  absorption,  the  blood-vessels  (portal 
tributaries)  and  the  lymphatic  vessels  or  lacteals.  In  general  terms, 
the  proteins  and  carbohydrates  are  absorbed  by  the  blood-vessels, 
and  the  fats  by  the  lacteals. 

Diffusion  and  osmosis  do  occur  in  the  intestine,  for  if  a  strong 
solution  of  salt  is  introduced  into  a  loop  of  intestine,  there  is  a  flow 
of  water  into  the  loop,  owing  to  the  high  osmotic  pressure  of  the  salt ; 
at  the  same  time  some  of  the  salt  diffuses  into  the  blood  in  accordance 
with  the  laws  of  diffusion.  But  if  some  of  the  animal's  own  serum 
is  introduced  into  the  loop,  it  also  is  absorbed,  although  it  has  the 

*  The  superficial  area  of  the  small  intestine,  if  it  was  flat,  is  about  To  square 
metres.     This  by  the  presence  of  the  villi  is  increased  to  about  42  square  metres. 

643 


544  THE   ABSORPTION   OF   FOOD  [CH.  XXXVI. 

same  osmotic  pressure  and  concentration  as  the  animal's  blood.  This 
experiment  alone  shows  us  that  known  physical  laws  will  not  com- 
pletely explain  absorption.  In  fact,  absorption  is  a  subject  upon 
which  we  can  speak  with  little  certainty ;  the  energy  that  controls 
it  is  doubtless  some  form  of  imbibition,  and  resides  in  the  living 
epithelium ;  for  if  the  epithelium  is  injured  or  destroyed  by  the 
action  of  such  a  poison  as  sodium  fluoride,  absorption  almost  ceases, 
and  what  does  occur  follows  the  laws  of  osmosis  and  diffusion. 

A  marked  feature  during  absorption  is  the  increased  activity  of 
the  lymphocytes  which  lie  beneath  the  epithelium ;  the  number  of 
these  cells  in  the  blood  increases  markedly ;  it  may  be  even  doubled. 
It  has,  therefore,  been  surmised  that  these  cells  share  in  the  work  of 
transporting  absorbed  materials. 

Absorption  of  Carbohydrates. — Though  the  sugar  formed  from 
starch  by  ptyalin  and  amylopsin  is  maltose,  that  found  in  the  blood 
is  glucose.  Under  normal  circumstances  little,  if  any,  is  absorbed  by 
the  lacteals.  The  glucose  is  formed  from  the  maltose  by  the  succus 
entericus,  aided  by  the  action  of  the  epithelial  cells  through  which  it 
passes.  Cane  sugar  and  milk  sugar  are  also  converted  into  mono- 
saccharides  before  absorption. 

The  carbohydrate  food  which  enters  the  blood  as  glucose  is  taken 
to  the  liver,  and  there  stored  up  in  the  form  of  glycogen — a  reserve 
store  of  carbohydrate  material  for  the  future  needs  of  the  body. 
Glycogen,  however,  is  found  in  animals  who  take  no  carbohydrate 
food.  It  must,  then,  be  formed  by  the  protoplasmic  activity  of  the 
liver  cells  from  their  protein  constituents  (see  preceding  chapter). 
Monosaccharides  (and  especially  glucose)  are  the  only  sugars  from  which 
the  liver  is  capable  of  forming  glycogen.  If  other  carbohydrates  such 
as  cane  sugar  or  lactose  are  injected  into  the  blood-stream  direct,  they 
are  unaltered  by  the  liver,  and  finally  leave  the  body  by  the  urine. 

Absorption  of  Proteins. — It  is  possible  for  the  alimentary  canal 
to  absorb  soluble  protein  in  an  unchanged  condition.  Thus,  after 
taking  a  large  number  of  eggs,  egg-albumin  is  found  in  the  urine. 
Patients  fed  per  rectum  derive  some  nourishment  from  protein  food, 
although  proteolytic  enzymes  are  absent  from  that  part  of  the 
intestine.  But  such  occurrences  are.  exceptional ;  they  are  merely 
illustrations  of  the  fact  that  under  unusual  conditions  certain  parts 
of  the  body  can  rise  to  the  occasion  and  perform  unusual  feats. 

The  normal  course  of  events  is  that  the  food  proteins  are  broken 
up  into  their  constituent  amino-acids,  and  it  is  in  this  form  that 
they  are  absorbed.  If  an  animal  receives,  instead  of  protein  the 
final  cleavage  ^  products  of  pancreatic  digestion,  it  continues  to 
maintain  its  nitrogenous  equilibrium;  that  is  to  say,  the  cells  of 
the  body  are  able  to  synthesise  tissue-proteins  from  the  fragments  of 
the  food  proteins. 


CII.  XXXVI.]  ABSORPTION  545 

It  is  somewhat  difficult  to  find  the  ammo-acids  iu  the  blood 
during  absorption,  for  several  reasons:  (1)  the  absorption  during 
any  given  time  is  slow,  and  the  products  are  diluted  with  the  whole 
volume  of  the  blood ;  (2)  the  presence  of  coagulable  proteins  in  the 
blood  in  large  quantity  renders  a  search  for  the  amino-acids  difficult ; 
and  (3)  when  the  amino-acids  get  into  the  blood  they  do  not 
accumulate  there,  but  are  rapidly  removed  by  the  cells  of  the 
tissues.  In  spite  of  these  difficulties,  Leathes,  Howell,  and,  later, 
Folin  have  succeeded  in  demonstrating  that  during  absorption  the 
non-protein  (that  is,  the  ammo-acid)  nitrogen  of  the  blood  increases. 
The  hypothesis  that  proteins  are  synthesised  during  absorption  in 
the  intestinal  wall  from  amino-acids  was  for  long  held  by  Abder- 
halden,  but  in  view  of  these  researches,  he  has  finally  aban- 
doned it. 

"We  have  now  a  rational  explanation  of  why  it  is  that  the 
organism  can  construct  the  proteins  peculiar  to  itself  and  maintain 
its  chemical  individuality,  although  the  food  taken  varies  so  widely 
in  composition. 

If  a  man  wants  to  build  a  house  from  the  bricks  of  another 
previously  built  house,  he  naturally  takes  the  latter  to  pieces  first, 
and  uses  the  bricks  most  suitable  for  his  purpose,  and  arranges  them 
in  a  different  way  to  their  previous  arrangement.  The  Germans 
have  recently  coined  the  expression  Bausteine  (or  building  stones) 
for  the  final  products  of  proteolysis  with  the  same  underlying  idea ; 
these  fragments  are  rearranged  by  the  tissue  cells  into  tissue- 
protein,  which  is  different  architecturally  from  the  food-protein. 

Abderhalden  has  published  a  very  striking  experiment  in  confirmation  of  this 
view.  He  collected  the  blood  of  a  horse,  separated  out  the  various  proteins  of  the 
plasma,  and  estimated  in  each  the  yield  of  certain  cleavage  products  (glutamic  acid 
and  tyrosine)  which  resulted  from  hydrolysis.  He  then  fed  the  horse  so  that  it 
formed  new  blood,  but  the  only  protein  given  was  gliadin,  a  vegetable  protein, 
which  is  remarkable  for  its  high  percentage  yield  (37-3)  of  glutamic  acid.  But  in 
the  regenerated  blood  proteins  the  percentage  yield  of  glutamic  acid  was  not 
increased  at  all ;  they  exactly  resembled  the  proteins  previously  present. 

It  is  a  far  cry  from  the  highly  specialised  organism  of  the  horse  to  the  proto- 
plasm of  the  simple  mould  known  as  Aspergillus  niger ;  nevertheless,  the  same 
general  rule  holds ;  the  protein  matter  present  yields  on  hydrolysis,  glycine, 
alanine,  leucine,  glutamic  and  aspartic  acids,  but  aromatic  products,  such  as 
tyrosine  and  phenylalanine,  were  not  discovered.  The  mould  was  then  cultivated 
on  media  of  widely  varying  composition,  but  the  protein  formed  in  the  living 
protoplasm  remained  constant  in  composition,  and  is  thus  independent  of  the 
composition  of  the  nutritive  medium. 

What,  then,  if  this  is  the  case,  would  be  the  fate  of  food  proteins  introduced 
directly  into  the  blood-stream  without  the  intervention  of  the  alimentary  digestive 
processes?  If  the  preliminary  cleavage  in  the  gastro-intestinal  tract  is  absol- 
utely necessary,  one  would  anticipate  that  a  foreign  food  protein  (such  as 
edestin  from  hemp  seed,  or  excelsin  from  Brazil  nuts)  administered  by  intravenous 
or  intraperitoneal  injection  would  not  be  assimilated,  but  would  be  cast  out  of  the 
body  in  one  or  more  of  the  excretions.  But  Mendel  and  Rockwood  found  that 
they  were  not  eliminated  in  either  urine  or  bile.  In  some  cases,  a  proteose 

2   M 


546  THE   ABSORPTION   OF   FOOD  [CH.  XXX VI. 

was  found  in  small  quantities  in  the  urine,  but  the  greater  part  of  the  protein 
administered  was  retained  in  the  body,  especially  if  the  injection  was  slowly 
performed. 

The  fact  that  proteins  are  retained  after  this  method  of  administration  and 
apparently  used  in  the  body  does  not  really  militate  against  the  theory  that 
proteins  under  normal  conditions  are  more  or  less  completely  broken  down  in  the 
alimentary  tract.  It  is  more  than  probable  that  cleavage  is  absolutely  necessary 
for  assimilation,  and  here  the  enzymes  present  in  the  tissue-cells  step  in  ;  they  are 
capable  of  taking  the  place  of  the  pancreatic  trypsin  and  intestinal  erepsin  and 
doing  their  work.  The  presence  of  a  proteose  in  urine  in  some  of  Mendel  and 
Rockwood's  experiments  points  in  this  direction,  and  this  view  is  supported  also 
by  Vernon's  discovery  that  every  tissue  of  the  body  has  an  ereptic  action, 
and  that  in  some  tissues  this  power  is  even  greater  than  in  the  intestinal  mucous 
membrane. 

It  must  not,  however,  be  supposed  that  all  the  building  stones  of 
the  food-protein  are  utilised  in  this  way.  The  body  is  remarkable 
for  its  economical  use  of  the  tissue-proteins,  and  quite  a  small 
quantity  relatively  is  used  up  in  our  daily  activities,  and  so  repair 
is  only  necessary  to  the  same  small  extent.  We  may  again  get 
some  assistance  from  our  example  of  the  man  building  a  house. 
When  he  takes  the  first  house  to  pieces,  there  will  be  a  lot  of 
useless  bricks  and  other  rubbish,  and  if  the  house  he  wants  to  build 
is  a  smaller  one  than  the  one  he  has  destroyed,  he  will  have  to  dis- 
card also  many  bricks  which  are  not  rubbish.  So  it  is  with  the 
fragments  of  the  food-protein,  which,  on  usual  diets,  are  more  abun- 
dant than  is  necessary  for  the  building  of  tissue-protein.  The  excess 
is  carried  to  the  liver,  where  the  amino-group  is  removed ;  this  is 
termed  dea  initiation :  the  nitrogenous  moiety  of  the  amino-acid  is 
then  converted  into  urea,  which  is  finally  discharged  from  the  body 
by  the  kidneys. 

It  should  be  further  noted  that  the  nitrogen  of  the  protein  is 
split  off  from  it  by  hydrolysis,  not  by  oxidation,  so  that  the  products 
of  breakdown  retain  almost  intact  the  previous  energy  of  the 
protein,  and  the  non-nitrogenous  residue  is  then  available  for  calorific 
processes  in  the  same  way  that  the  non-nitrogenous  foods  (carbo- 
hydrates and  fat)  are. 

To  continue  our  analogy  of  the  house-builder,  it  is  generally 
found  that  in  addition  to  the  building  stones  provided  from  the 
destruction  of  the  previous  house,  he  may  want  some  new  bricks 
altogether.  Is  this  a  possibility  in  the  body  ?  Again  recent  research 
answers  this  question  in  the  affirmative,  and  has  shown  that  the 
body-cells  possess  a  previously  unsuspected  power  of  synthesising 
amino-acids  for  themselves.  We  shall  return  to  this  in  the 
chapter  on  metabolism. 

Absorption  of  Pats.— The  fats  undergo  in  the  intestine  two 
changes :  one  a  physical  change  (emulsification),  the  other  a  chemical 
change  (saponification).  The  lymphatic  vessels  are  the  great  channels 


CH.  XXXVI.] 


ABSORPTION   OF   FATS 


547 


for  fat  absorption,  and  their  name  lacteals  is  derived  from  the  milk- 
like  appearance  of  their  contents  (chyle)  during  the  absorption  of  fat. 

The  course  which  the 
minute  fat  -  globules  take 
may  be  studied  by  killing 
animals  at  varying  periods 
after  a  meal  of  fat,  and 
making  osmic  acid  micro- 
scopic preparations  of  -the 
villi.  Figs.  366  and  367 
illustrate  the  appearances 
observed. 

The  columnar  epithelium 
cells  become  first  filled  with 
fatty  globules  of  varying 
size,  which  are  generally 
larger  near  the  free  border. 
The  globules  pass  down  the 
cells,  the  larger  ones  break- 
ing up  into  smaller  ones 
during  the  journey;  they 
are  then  transferred  to  the 
amosboid  cells  of  the  lym- 
phoid  tissue  beneath :  these 
ultimately  penetrate  into 
the  central  lacteal,  where 
they  either  disintegrate  or 
discharge  their  cargo  into  the  lymph-stream.  The  globules  are  by  this 
time  divided  into  immeasurably  small  ones,  the  molecular  basis  of  chyle. 
The  chyle  enters  the  blood-stream  by 
the  thoracic  duct,  and  after  an  abun- 
dant fatty  meal  the  blood-plasma  is 
quite  milky;  the  fat  droplets  are  so 
small  that  they  circulate  without  hind- 
rance through  the  capillaries.  The  fat 
in  the  blood  after  a  meal  is  eventu- 
ally stored  up  especially  in  the  cells 
of  adipose  tissue.  It  must,  however, 
be  borne  in  mind  that  the  fat  of  the 
body  is  not  exclusively  derived  from 
the  fat  of  the  food,  but  it  may  origin- 
ate from  carbohydrate,  and  according 
to  some  observers  from  protein  also. 

The  great  difficulty  in  fat  absorption  was  to  explain  how  the  fat 
first  gets  into  the  columnar  epithelium :  these  cells  will  not  take  up 


FIG.  366. — Section  of  the  villus  of  a  rat  killed  during  fat 
absorption,  cp,  Epithelium;  sir,  striated  border; 
c,  lymph-cells ;  c',  lymph-cells  in  the  epithelium ; 
I,  central  lacteal  containing  disintegrating  lymph- 
corpuscles.  (E.  A.  Schiifer.) 


FIG.  367.— Mucous  membrane  of  frog's  intes- 
tine during  fat  absorption,  ep,  Epithe- 
lium ;  str,  striated  border;  C,  lymph 
corpuscles  ;  I,  lacteal.  (E.  A.  Schiifer.) 


548  THE    ABSORPTION   OF   FOOD  [CH.  XXXVI. 

other  particles,  and  it  is  certain  that  the  epithelial  cells  do  not 
protrude  pseudopodia  from  their  borders  (this,  however,  does  occur 
in  the  endoderm  of  some  of  the  lower  invertebrates) ;  moreover,  fat 
particles  have  never  been  seen  in  the  striated  border  of  the  cells. 

The  difficulty  has  now  been  solved.  Munk  and,  later,  Moore  and 
Eockwood,  showed  quite  conclusively  that  in  the  intestine  fat  is 
completely  broken  down  into  glycerin  and  fatty  acids ;  preliminary 
emulsification  is  advantageous  for  the  formation  of  these  substances, 
but  is  not  essential.  Fat,  therefore,  is  entirely  absorbed  as  glycerin 
and  fatty  acids;  the  latter,  however,  in  great  measure  are  first 
converted  into  soaps,  that  is,  compounds  of  the  fatty  acids  and 
alkalis.  These  soluble  cleavage  products  pass  readily  through  the 
striated  borders  of  the  intestinal  epithelial  cells;  and  these  cells 
perform  the  synthetic  act  of  building  them  into  fat  once  more,  the 
fat  so  formed  appearing  in  the  form  of  small  globules,  surrounding 
or  becoming  mixed  with  the  protoplasmic  granules  that  are  ordi- 
narily present.  Another  remarkable  fact  which  Munk  made  out  is 
that  after  feeding  an  animal  on  fatty  acids  the  chyle  contains  fat. 
The  necessary  glycerin  must  have  been  formed  by  protoplasmic 
activity  during  absorption. 

Bile  aids  the  digestion  of  fat,  the  bile  salts  acting  in  the  same  way 
as  the  co-enzyme  of  pancreatic  lipase ;  bile  also  is  a  solvent  of  fatty 
acids,  and  it  probably  assists  fat  absorption  by  reducing  the  surface 
tension  of  the  intestinal  contents;  membranes  moistened  with  bile 
allow  fatty  materials  to  pass  through  them  more  readily  than  would 
otherwise  be  the  case.  In  cases  of  disease  in  which  bile  is  absent 
from  the  intestines,  a  large  proportion  of  the  fat  in  the  food  passes 
into  the  faeces. 

The  faeces  on  an  ordinary  mixed  diet  contain  comparatively 
little  food  residues,  and  a  small  quantity  is  excreted  even  during 
starvation.  Voit  and  Hermann  showed  independently  that  an 
intestinal  loop  which  had  been  emptied  and  separated  from  the 
rest  of  the  bowel  contained  a  few  days  later,  material  identical  with 
faeces,  and  consisting  of  intestinal  juice,  desquamated  epithelium 
cells,  and  bacteria.  The  increase  in  the  amount  of  fasces  which 
occurs  when  food  is  taken,  even  when  the  food  is  free  from  cellulose, 
is  due  to  the  mechanical  and  chemical  stimulation  which  leads  to 
an  increase  in  the  succus  entericus,  and  in  the  shedding  of  epithelial 
cells.  The  faeces  contain  about  1  per  cent,  of  nitrogen,  but  this 
is  chiefly  contained  in  the  bodies  of  bacteria,  and  the  disintegrated 
epithelial  cells.  Addition  of  protein  to  the  diet  makes  practically 
no  difference  to  the  nitrogen  in  the  faeces  under  normal  conditions. 

The  addition  of  cellulose  to  the  diet  increases  the  bulk  of  the 
faeces,  partly  because  much  of  the  cellulose  is  excreted  unchanged, 
partly  because  it  stimulates  the  mucous  membrane  to  secrete  more 


CH.  XXXVI.]  THE  MCES  549 

succus  entericus,  and  finally  because  the  larger  food  residue  favours 
the  development  of  bacteria.  On  an  average,  from  one-third  to 
one-fifth  (varying  with  the  diet)  of  the  weight  of  dried  faeces 
consists  of  bacteria.  The  average  weight  of  dried  bacteria  excreted 
daily  is  8  grammes ;  this  contains  0-8  gramme  of  nitrogen,  or  about 
half  the  nitrogen  of  the  faeces.  Strasburger  estimated  that  about 
128,000,000,000,000  bacteria  are  evacuated  in  the  fasces  of  a  man 
every  day.  The  vast  majority  of  these  are  dead. 

When  cellulose  is  absent  from  the  diet,  the  faeces  contain  from 
65-75  per  cent,  of  water;  the  dry  residue  contains  about  7  per  cent, 
of  nitrogen,  and  the  non-nitrogenous  material  consists  of  about 
equal  quantities  of  ash  and  substances  soluble  in  ether,  with  small 
quantities  of  stercobilin  and  other  bile  residues.  The  ash  contains 
mainly  calcium  phosphate,  with  small  amounts  of  iron  and 
magnesium.  The  ethereal  extract  contains  cholesterin,  lecithin,  fatty 
acids,  soaps,  and  a  very  small  amount  of  neutral  fat.  The  proteins 
are  chiefly  mucin  and  nucleo-protein,  and  are  derived  not  from  the 
food,  but  from  the  intestinal  wall,  or  are  contained  in  the  bacteria ; 
no  doubt  a  large  part  of  the  ethereal  extract  is  also  supplied  by 
the  bacteria. 

Cellulose  is  thus  the  only  important  constituent  of  the  food 
which  is  unaffected  by  the  digestive  juices,  although  a  variable 
amount,  which  is  largest  in  herbivorous  animals,  undergoes  bacterial 
decomposition.  The  presence  of  cellulose  also  interferes  with  the 
absorption  of  proteins,  for  the  digestive  juices  have  difficulty  in 
penetrating  the  cellulose  membranes  of  vegetable  cells.  Thus  Voit 
found  that  42  per  cent,  of  the  nitrogen  in  the  food  were  lost  in  the 
faeces  of  a  vegetarian.  This  is  due  solely  to  the  cellulose  and  not 
to  any  difference  in  the  digestibility  of  animal  and  vegetable  proteins, 
for  if  vegetable  food  is  finely  subdivided,  and  then  thoroughly  cooked 
and  softened,  this  loss  is  lessened,  and  if  vegetable  protein  is 
entirely  freed  from  cellulose,  it  is  as  thoroughly  absorbed  as  animal 
protein.  Fifteen  per  cent,  of  the  dry  substance  of  green  vegetables 
and  brown  bread,  20  per  cent,  of  carrots  and  turnips,  and  a  still 
larger  amount  of  beans  are  lost  in  the  faecal  residue. 

The  intestinal  contents  travel  more  rapidly  when  vegetables  are 
present,  for  the  indigestible  cellulose  stimulates  peristalsis,  and  there- 
fore a  large  quantity  of  water  escapes  absorption  in  the  colon.  Thus 
on  an  ordinary  mixed  diet  35  grammes  of  dry  substance  and  100 
grammes  of  water  are  daily  excreted  in  the  faeces,  whereas  on  a 
vegetable  diet  the  quantities  are  75  and  260  grammes  respectively. 


CHAPTER   XXXVII 

THE   MECHANICAL   PROCESSES   OF   DIGESTION 

UNDER  this  head  we  shall  study  the  neuro-muscular  mechanism  of  the 
alimentary  canal,  which  has  for  its  object  the  onward  movement  of 
the  food,  and  its  thorough  admixture  with  the  digestive  juices.  We 
shall  therefore  have  to  consider  mastication,  deglutition,  the  move- 
ments of  the  stomach  and  intestines,  defsecation,  and  vomiting. 

MASTICATION. 

The  act  of  mastication  is  performed  by  the  biting  and  grinding 
movement  of  the  lower  range  of  teeth  against  the  upper.  The 
simultaneous  movements  of  the  tongue  and  cheeks  assist  partly  by 
crushing  the  softer  portions  of  the  food  against  the  hard  palate  and 
gums,  and  thus  supplement  the  action  of  the  teeth,  and  partly  by 
returning  the  morsels  of  food  to  the  teeth  again  and  again,  as 
they  are  squeezed  out  from  between  them,  until  they  have  been 
sufficiently  chewed. 

The  act  of  mastication  is  much  assisted  by  the  saliva,  and  the 
intimate  incorporation  of  this  secretion  with  the  food  is  called 
insalivation. 

Mastication  is  much  more  thoroughly  performed  by  some  animals 
than  by  others.  Thus,  dogs  hardly  chew  their  food  at  all,  but  the 
oesophagus  is  protected  from  abrasion  by  a  thick  coating  of  very 
viscid  saliva  which  lubricates  the  pieces  of  rough  food. 

In  vegetable  feeders,  on  the  other  hand,  insalivation  is  a  much 
more  important  process.  This  is  especially  so  in  the  ruminants ;  in 
these  animals,  the  grass,  etc.,  taken,  is  hurriedly  swallowed,  and  passes 
into  the  first  compartment  of  their  four-chambered  stomach.  Later 
on,  it  is  returned  to  the  mouth  in  small  instalments  for  thorough 
mastication  and  insalivation ;  this  is  the  act  of  rumination,  or 
"  chewing  the  cud " ;  the  food  is  then  once  more  swallowed,  and 
passes  on  to  the  digestive  regions  of  the  stomach. 

650 


CH.  XXXVII.]  DEGLUTITION  551 

In  man,  mastication  is  also  an  important  process,  and  in  people 
who  have  lost  their  teeth  severe  dyspepsia  is  often  produced,  which 
can  be  cured  by  a  new  set  of  teeth. 

DEGLUTITION. 

When  properly  masticated,  the  food  is  transmitted  in  successive 
portions  to  the  stomach  by  the  act  of  deglutition  or  swallowing. 
This,  for  the  purpose  of  description,  may  be  divided  into  three  acts. 
In  the  first,  particles  of  food  collected  as  a  bolus  are  made  to  glide 
between  the  surface  of  the  tongue  and  the  palatine  arch,  till  they 
have  passed  the  anterior  arch  of  the  fauces ;  in  the  second,  the  morsel 
is  carried  through  the  pharynx;  and  in  the  third,  it  reaches  the 
stomach  through  the  oesophagus.  These  three  acts  follow  each  other 
rapidly.  (1)  The  first  act  is  voluntary,  although  it  is  usually  per- 
formed unconsciously;  the  morsel  of  food  when  sufficiently  masti- 
cated, is  pressed  between  the  tongue  and  palate,  by  the  agency  of  the 
muscles  of  the  former,  in  such  a  manner  as  to  force  it  back  to  the 
entrance  of  the  pharynx.  (2)  The  second  act  is  the  most  complicated, 
because  the  food  must  go  past  the  posterior  orifice  of  the  nose  and 
the  upper  opening  of  the  larynx  without  entering  them.  When  it 
has  been  brought,  by  the  first  act,  between  the  anterior  arches  of  the 
palate,  it  is  moved  onwards  by  the  movement  of  the  tongue  backwards, 
and  by  the  muscles  of  the  anterior  arches  contracting  on  it  and  then 
behind  it.  The  root  of  the  tongue  being  retracted,  and  the  larynx 
being  raised  with  the  pharynx  and  carried  forwards  under  the  base 
of  the  tongue,  the  epiglottis  is  pressed  over  the  upper  opening  of  the 
larynx,  and  the  morsel  glides  past  it;  the  closure  of  the  glottis  is 
additionally  secured  by  the  simultaneous  contraction  of  its  own 
muscles :  so  that,  even  when  the  epiglottis  is  destroyed,  there  is  little 
danger  of  food  passing  into  the  larynx  so  long  as  its  muscles  can  act 
freely.  In  man,  and  some  other  animals,  the  epiglottis  is  not  drawn 
as  a  lid  over  the  larynx  during  swallowing.  At  the  same  time,  the 
raising  of  the  soft  palate,  so  that  its  posterior  edge  touches  the  back 
part  of  the  pharynx,  and  the  approximation  of  the  sides  of  the 
posterior  palatine  arch,  which  move  quickly  inwards  like  side  curtains, 
close  the  passage  into  the  upper  part  of  the  pharynx  and  the  posterior 
nares,  and  form  an  inclined  plane,  along  the  under  surface  of  which 
the  morsel  descends ;  then  the  pharynx,  raised  up  to  receive  it,  in  its 
turn  contracts,  and  forces  it  onwards  into  the  oesophagus.  The  passage 
of  the  bolus  of  food  through  the  three  constrictors  of  the  pharynx  is 
the  last  step  in  this  stage.  (3)  In  the  third  act,  in  which  the  food 
passes  through  the  oesophagus,  every  part  of  that  tube,  as  it  receives 
the  morsel  and  is  dilated  by  it,  is  stimulated  to  contract :  hence  an 
undulatory  or  peristaltic  contraction  of  the  oesophagus  occurs.  If  we 
suppose  the  bolus  to  be  at  one  particular  place  in  the  tube,  it  acts 


552  THE  MECHANICAL  PROCESSES   OF   DIGESTION    [CH.  XXXYII. 

stimulatingly  on  the  circular  muscular  fibres  behind  it,  and  inhibit- 
ingly  on  those  in  front ;  the  contraction  therefore  squeezes  it  into  the 
dilated  portion  of  the  tube  in  front,  where  the  same  process  is 
repeated,  and  this  travels  along  the  whole  length  of  the  tube.  The 
second  and  third  parts  of  the  act  of  deglutition  are  involuntary.  The 
action  of  these  parts  is  more  rapid  than  peristalsis  usually  is.  This 
is  due  to  the  large  amount  of  striated  muscular  tissue  present.  It 
serves  the  useful  purpose  of  getting  the  bolus  as  quickly  as  possible 
past  the  opening  of  the  respiratory  tract. 

The  swallowing  both  of  solids  and  liquids  is  a  muscular  act,  and 
can,  therefore,  take  place  in  opposition  to  the  force  of  gravity. 
Thus,  horses  and  many  other  animals  habitually  drink  uphill,  and 
the  same  feat  can  be  performed  by  jugglers. 

In  swallowing  liquids  the  two  mylo-hyoid  muscles  form  a 
diaphragm  below  the  anterior  part  of  the  mouth.  The  stylo-glossi 
draw  the  tongue  backwards  and  elevate  its  base ;  the  two  hyo-glossi 
act  with  these,  pulling  the  tongue  backwards  and  downwards.  The 
action  of  these  muscles  resembles  that  of  a  force-pump  projecting  the 
mass  of  fluid  down  into  the  oesophagus ;  it  reaches  the  cardiac  orifice 
with  great  speed,  and  the  pharyngeal  and  cesophageal  muscles  do  not 
contract  on  it  at  all,  but  are  inhibited  during  the  passage  of  the  fluid 
through  them  (Kronecker). 

This  is  proved  in  a  striking  way  in  cases  of  poisoning  by  corro- 
sive substances,  such  as  oil  of  vitriol;  the  mouth  and  tongue  are 
scarred  and  burnt,  but  the  pharynx  and  oesophagus  escape  serious 
injury,  so  rapidly  does  the  fluid  pass  along  them;  the  cardiac 
orifice  of  the  stomach  is  the  next  place  to  show  the  effects  of  the 
corrosive.  Kronecker's  view  has  also  been  confirmed  in  man  by 
the  X-ray  method. 

There  is,  however,  no  hard-and-fast  line  between  the  swallowing 
of  solids  and  fluids :  the  more  liquid  the  food  is,  the  more  does  the 
force-pump  action  just  described  manifest  itself. 

Nervous  Mechanism. — The  nerves  engaged  in  the  reflex  act  of 
deglutition  are  -.—sensory,  branches  of  the  fifth  cranial  nerve  supplying 
the  soft  palate  and  tongue;  glosso-pharyngeal,  supplying  the  tongue 
and  pharynx ;  the  superior  laryngeal  branch  of  the  vagus,  supplying 
the  epiglottis  and  the  glottis ;  while  the  motor  fibres  concerned  are : — 
branches  of  the  fifth,  supplying  part  of  the  digastric  and  mylo-hyoid 
muscles,  and  the  muscles  of  mastication;  the  bulbar  part  of  the 
spinal  accessory  through  the  pharyngeal  plexus,  supplying  the  levator 
palati,  probably  by  rootlets  which  are  glosso-pharyngeal  in  origin  ;  the 
glosso-pharyngeal  and  vagus,  and  possibly  the  bulbar  part  of  the  spinal 
accessory,  supplying  the  muscles  of  the  pharynx  through  the  phar- 
yngeal ^  plexus;  the  vagus,  in  virtue  of  its  spinal  accessory  roots, 
supplying  the  muscles  of  the  larynx  through  the  inferior  laryngeal 


CH.  XXXVII.]  MOVEMENTS    OF  THE   STOMACH  553 

branch;  and  the  hypo-glossal,  the  muscles  of  the  tongue.  The 
nerre-centres  by  which  the  muscles  are  harmonised  in  their  action, 
are  situated  in  the  medulla  oblongata. 

Stimulation  of  the  vagi  gives  rise  to  peristalsis  of  the  oesophagus. 
The  cell-stations  of  these  fibres  are  in  the  ganglion  trunci  vagi. 
Division  of  both  pneumogastric  nerves  produces  paralysis  of  the 
oesophagus  and  stomach,  and  firm  contraction  of  the  cardiac  orifice. 
These  nerves  therefore  normally  supply  the  oesophagus  with  motor, 
and  the  cardiac  sphincter  with  inhibitory  fibres.  If  food  is  swallowed 
after  these  nerves  are  divided,  it  accumulates  in  the  gullet  and  never 
reaches  the  stomach. 

In  discussing  peristalsis  on  a  previous  occasion  (p.  141),  we 
arrived  at  the  conclusion  that  it  is  an  inherent  property  of  muscle 
rather  than  of  nerve;  though  normally  it  is  controlled  and  influenced 
by  nervous  agency.  This  nervous  control  is  especially  marked  in  the 
oesophagus;  for  if  that  tube  is  divided  across,  leaving  the  nerve 
branches  intact,  a  wave  of  contraction  will  travel  from  one  end  to  the 
other  across  the  cut. 


MOVEMENTS  OF  THE  STOMACH. 

The  gastric  fluid  is  assisted  in  accomplishing  its  share  in  digestion 
by  the  movements  of  the  stomach.  In  graminivorous  birds,  for 
example,  the  contraction  of  the  strong  muscular  gizzard  affords  a 
necessary  aid  to  digestion,  by  grinding  and  triturating  the  hard 
seeds  which  constitute  their  food.  But  in  the  stomach  of  man  and 
other  Mammalia  the  movements  of  the  muscular  coat  are  too  feeble 
to  exercise  any  such  mechanical  force  on  the  food;  neither  are 
they  needed,  for  mastication  has  already  done  the  mechanical  work 
of  a  gizzard ;  and  it  has  been  demonstrated  that  substances  are 
digested  even  when  enclosed  in  perforated  tubes,  and  consequently 
protected  from  mechanical  influence. 

When  digestion  is  not  going  on,  the  stomach  is  uniformly  con- 
tracted, its  orifices  not  more  firmly  than  the  rest  of  its  walls ;  but, 
if  examined  shortly  after  the  introduction  of  food,  it  is  found  closely 
encircling  its  contents,  and  its  orifices  are  firmly  closed  by  sphincters. 
The  cardiac  orifice,  every  time  food  is  swallowed,  opens  to  admit  its 
passage  into  the  stomach,  and  immediately  again  closes.  The  pyloric 
orifice,  during  the  first  part  of  gastric  digestion,  is  usually  so  com- 
pletely closed,  that  even  when  the  stomach  is  separated  from  the 
intestines,  none  of  its  contents  escape.  But  later  the  pylorus  offers 
less  resistance  to  the  passage  of  substances  from  the  stomach ;  first 
it  yields  to  allow  the  successively  digested  portions  to  go  through 
it ;  and  then  it  allows  the  transit  even  of  undigested  substances. 
The  peristaltic  action  of  the  muscular  coat,  whereby  the  digested 


554  THE   MECHANICAL   PROCESSES    OF   DIGESTION     [CH.  XXXV1L 

portions  are  gradually  moved  towards  the  pylorus,  also  ensures 
thorough  admixture  with  the  gastric  juice. 

The  contraction  of  the  fibres  situated  towards  the  pyloric  end  of 
the  stomach  is  more  energetic  and  more  decidedly  peristaltic 
than  those  of  the  cardiac  portion.  Thus,  it  was  found  in  the  case  of 
St  Martin,  that  when  the  bulb  of  a  thermometer  was  placed  about 
three  inches  from  the  pylorus,  through  the  gastric  fistula,  it  was 
tightly  embraced  from  time  to  time,  and  drawn  towards  the  pyloric 
orifice  for  a  distance  of  three  or  four  inches.  In  certain  patho- 
logical conditions,  by  a  predominant  action  of  strong  circular 
fibres  placed  between  the  cardia  and  pylorus,  the  two  portions,  or 
ends,  as  they  are  called,  of  the  stomach,  are  partially  separated  from 
each  other  by  a  kind  of  hour-glass  contraction. 

A  few  years  ago  the  subject  was  taken  up  by  Cannon.  He  gave 
an  animal  food  mixed  with  bismuth  subnitrate,  and  obtained  by  the 
Kontgen  rays  shadow  photographs  of  the  stomach,  because  the 
bismuth  salt  renders  its  contents  opaque.  His  results  confirm  those 
of  the  earlier  investigators;  the  principal  peristalsis  occurs  in  the 
pyloric  portion  of  the  stomach.  The  cardiac  portion  (including  the 
fundus)  presses  steadily  on  its  contents,  and  as  they  become  chymified, 
urges  them  onwards  towards  the  pyloric  portion ;  the  latter  empties 
itself  gradually  through  the  pylorus  into  the  duodenum,  and  in  the 
later  stages  of  digestion  the  cardiac  part  also  is  constricted  into  a  tube. 

After  an  ordinary  mixed  meal  it  is  usually  stated  that  the 
pylorus  usually  opens  for  the  first  time  about  half  an  hour  after 
digestion  begins,  and  some  of  the  acid  chyme  passes  into  the 
duodenum.  This,  however,  is  incorrect,  as  food  can  be  seen  by  the 
X-ray  method  in  the  duodenum  within  a  few  minutes  after  a  meal. 
The  action  of  this  muscular  ring  is  intermittent,  and  the  explanation 
of  its  alternate  openings  and  closings  may  be  briefly  summed  up  in 
the  phrase  used  by  Cannon  :  "  the  acid  control  of  the  pylorus."  It  is 
necessary  that  the  food  should  be  retained  in  the  stomach  until  it  is 
acid ;  otherwise  it  would  not,  on  reaching  the  duodenum,  give  rise 
to  the  formation  of  secretin,  the  chemical  stimulus  for  the  flow  of 
pancreatic  juice,  and  bile.  He  has  found  that  acid  on  the  gastric  side 
of  the  pyloric  sphincter  opens  it,  and  acid  in  the  duodenum  closes  it. 
As  soon  therefore  as  the  chyme  is  neutralised  by  the  alkaline  juices 
of  the  duodenum,  there  is  no  longer  any  hindrance  to  the  action  of 
the  acid  chyme  in  the  pyloric  end  of  the  stomach  in  opening  the 
door  which  was  temporarily  closed  by  acid  on  its  duodenal  side. 
This  action  does  not  occur  if  a  ring  is  cut  through  the  muscular 
coat  immediately  beyond  the  pylorus,  and  so  the  effect  from  the 
duodenum  is  a  local  reflex  action  mediated  like  the  movements  of 
the  small  intestine  by  the  plexus  of  Auerbach. 

The  time  taken   for  the  complete  emptying  of  the  stomach  is 


CH.  XXXVII.] 


MOVEMENTS   OF  THE   STOMACH 


555 


variable;  the  size  of  the  meal,  its  digestibility,  the  general  state  of 
the  body  and  mind  of  the  individual,  are  all  factors  that  influence  the 
rate  of  the  act.  The  average  time,  however,  is  probably  somewhere 
about  three  hours. 

Dr  Hertz  and  his  colleagues  at  Guy's  Hospital  have  recently 
applied  the  Bdntgen  ray  method  to  man  with  very  instructive 
results.  Large  doses  of  bismuth  oxychloride  (or  barium  sulphate) 
can  be  given  to  human  beings  without  harm,  and  by  the  X-rays  the 
shadow  of  the  opaque  food  can  then  be  followed,  from  swallowing 
onwards  to  defecation.  The  old  ideas  of  the  shape  and  position  of 
the  stomach  during  life,  which  were  derived  from  examining  it  in 
the  post-mortem  room,  are  wholly  incorrect.  In  the  upright  position 
the  pyloric  portion  is  lowermost,  and  when  food  is  taken  it  sinks 
into  this  lower  portion ;  and  above  the  ordinary  semi-fluid  contents 
there  is  a  horizontal  upper  limit  above  which  is  air.  In  the  erect 
position  the  stomach,  however,  is  not  quite  vertical,  but  is  usually 
slightly  inclined  towards  the  right;  and  in  the  recumbent  position 
this  obliquity  is  increased.  The  following  three  figures  illustrate 
the  shape  and  position  of  the  stomach  when  the  man  is  erect : — 
(a)  when  the  organ  is  empty;  (6)  when  it  is  partly  filled;  and  (c) 
when  it  is  full. 


FIG.  368.— (a)  View  of  the  empty  stomach  in  vertical  position ;  (b)  stomach  as  seen  soon  after  a 
bismuth  meal ;  note  the  peristaltic  waves  at  the  pyloric  end  ;  (c)  view  of  filled  stomach  in  vertical 
position.  (After  Hertz  ) 


Peristalsis,  as  in  animals,  is,  during  the  early  stages  of  gastric 
digestion,  limited  to  the  pyloric  portion.  But  the  view  that  the 
stomach  is  separated  into  two  divisions  in  one  of  which  (the  fundus) 
salivary  digestion  is  in  progress,  and  in  other  of  which  gastric 
digestion  proper  is  progressing,  is  quite  untenable  in  view  of  these 
observations,  especially  if  changes  of  posture  are  occurring  also. 

The  fluidity  of  the  food  is  another  factor  which  is  important; 
the  more  fluid  the  food,  the  more  rapidly  does  it  leave  the  stomach. 
If  water  is  given  to  a  dog  with  a  duodenal  fistula,  it  flows  out  of  the 


556  THE   MECHANICAL  PROCESSES   OF  DIGESTION     [CH.  XXXTII. 

opening  almost  as  rapidly  as  it  is  swallowed.  It  is  impossible  in 
man  to  follow  the  behaviour  of  water  by  X-ray  shadows,  but  Hertz 
finds  that  the  more  fluid  his  bismuth  mixture  is,  the  more  rapidly 
does  it  issue  into  the  intestine.  The  rapid  relief  of  thirst  which 
follows  the  drinking  of  water,  and  the  superiority  of  fluid  food  for 
the  restoration  of  persons  who  are  faint  for  want  of  nourishment,  are 
further  facts  which  point  to  the  rapid  arrival  of  liquids  at  the 
absorbing  surface  of  the  intestine. 

Nervous  Mechanism. — The  stomach  has  a  double  nerve  supply, 
and  the  fibres  terminate  in  the  plexus  situated  between  its  muscular 
coats.  The  two  sets  of  nerves  are  : — 

(1)  The  vagus.     The  cell-stations  for  these  fibres  appear  to  be 
in  the  terminal  ganglia  of  the  plexus,  though  possibly  some  may 
occur  in  the  ganglion  trunci  vagi.     These  nerves  are  accelerator ; 
when  stimulated,  the  result  is  increase  of  peristalsis. 

(2)  The  sympathetic.     These  leave  the  spinal  cord  by  the  anterior 
roots  of  the  spinal  nerves  from  the  fifth  to   the  eighth  thoracic ; 
their  cell-stations  are  in  the  coeliac  ganglion,  and  the  post-ganglionic 
fibres  which  arise  there   pass  to  the  stomach  by  branches  of  the 
splanchnic  nerves.     The   sympathetic   fibres  are   inhibitory;   when 
they  are  stimulated,  peristalsis  ceases. 

The  secretory  nerves  of  the  gastric  glands  are  discussed  on  p.  512. 

VOMITING. 

The  act  of  vomiting  is  preceded  by  a  feeling  of  nausea,  and  the 
swallowing  of  a  large  quantity  of  saliva.  The  expulsion  of  the  con- 
tents of  the  stomach,  like  that  of  mucus  or  other  matter  from  the 
lungs  in  coughing,  is  preceded  by  an  inspiration  ;  the  glottis  is  then 
closed,  and  immediately  afterwards  the  abdominal  muscles  strongly 
act ;  but  here  occurs  the  difference  in  the  two  actions.  Instead  of 
the  vocal  cords  yielding  to  the  action  of  the  abdominal  muscles,  they 
remain  tightly  closed.  Thus  the  diaphragm,  being  unable  to  go  up, 
forms  an  unyielding  surface  against  which  the  stomach  can  be 
pressed.  At  the  same  time  the  cardiac  sphincter  being  relaxed,  and 
the  orifice  which  it  naturally  guards  being  dilated,  while  the  pylorus 
is  closed,  and  the  stomach  itself  also  contracting,  the  action  of  the 
abdominal  muscles  expels  the  contents  of  the  organ  through  the 
oesophagus,  pharynx,  and  mouth. 

It  has  been  frequently  stated  that  the  stomach  itself  is  quite 
passive  during  vomiting,  and  that  the  expulsion  of  its  contents  is 
effected  solely  by  the  pressure  exerted  upon  it  when  the  capacity  of 
the  abdomen  is  diminished  by  the  contraction  of  the  diaphragm,  and 
subsequently  of  the  abdominal  muscles.  The  experiments  and 
observations,  however,  which  are  supposed  to  confirm  this  statement, 


CH.  XXXVII.]  INTESTINAL   MOVEMENTS  557 

only  show  that  the  contraction  of  the  abdominal  muscles  alone  is 
sufficient  to  expel  matters  from  an  unresisting  bag  through  the 
oesophagus;  and  that,  under  certain  circumstances,  the  stomach, 
by  itself,  cannot  expel  its  contents.  They  by  no  means  show  that  in 
ordinary  vomiting  the  stomach  is  passive,  for  there  are  good  reasons 
for  believing  the  contrary.  In  some  cases  of  violent  vomiting  the 
contents  of  the  duodenum  are  passed  by  anti-peristalsis  into  the 
stomach,  and  are  then  vomited.  Where  there  is  obstruction  to  the 
intestine,  as  in  strangulated  hernia,  the  total  contents  of  the  small 
intestine  may  be  vomited. 

Nervous  Mechanism. — Some  few  persons  possess  the  power  of 
vomiting  at  will,  or  the  power  may  be  acquired  by  effort  and  practice. 
But  normally  the  action  is  a  reflex  one. 

The  afferent  nerves  are  principally  the  fifth,  and  glosso-pharyngeal 
(as  in  vomiting  produced  by  tickling  the  fauces),  and  the  vagus  (as 
in  vomiting  produced  by  gastric  irritants) ;  but  vomiting  may  occur 
from  stimulation  of  other  sensory  nerves,  e.g.,  those  from  the  kidney, 
uterus,  testicle,  etc.  The  medullary  centres  may  also  be  stimulated 
by  impressions  from  the  cerebrum  and  cerebellum,  producing  so-called 
central  vomiting  occurring  in  diseases  of  those  parts. 

The  efferent  (motor)  impulses  are  carried  by  the  vagi  to  the 
stomach,  by  the  phrenics  to  the  diaphragm,  and  by  various  other 
spinal  nerves  to  the  abdominal  muscles. 

It  is  very  doubtful  whether  there  is  any  separate  centre  for 
vomiting ;  the  centre  for  the  reflex  coincides  with  those  of  the  nerves 
mentioned  in  the  medulla  oblongata. 

Emetics. — Some  emetics  produce  vomiting  by  irritating  the 
stomach ;  others,  such  as  tartar  emetic,  apomorphine,  etc.,  by  stimu- 
lating the  medullary  centres. 

MOVEMENTS  OF  THE  SMALL  INTESTINE. 

The  intestinal  movements,  like  those  of  the  stomach,  take  place 
independently  of  our  volition  or  consciousness.  When,  however, 
they  become  excessive,  as  they  do  under  the  influence  of  irritants  or 
the  presence  of  obstruction,  they  produce  pain  which  is  usually  intense. 

The  object  of  these  movements  is  to  force  the  contents  along  the 
tube,  and  to  thoroughly  mix  them  with  the  digestive  juices.  But 
the  peristalsis  which  drives  the  intestinal  contents  along  does  so 
more  slowly  than  that  which  occurs  in  the  oesophagus;  otherwise 
the  mechanism  is  much  the  same.  There  may  occur  in  the  small 
intestine  peristaltic  waves  in  the  opposite  direction  (retro-peristalsis) 
and  this  probably  never  occurs  in  the  oesophagus.  .Retro -peristalsis 
is  most  marked  when  obstruction  is  present,  as  in  the  cases  of 
violent  vomiting  just  referred  to. 


558  THE   MECHANICAL   PROCESSES    OF   DIGESTION     [CH.  XXXVII. 

Our  knowledge  of  the  intestinal  movements  rests,  first,  on 
observations  made  on  the  exposed  intestines  when  the  abdomen  is 
opened;  secondly,  they  may  be  studied  under  more  artificial 
conditions  by  taking  a  length  of  intestine  from  a  freshly  killed 
animal  and  placing  it  in  a  warm  bath  of  oxygenated  Kinger's 
solution;  and  thirdly,  the  most  valuable  method  of  all  is  to  study 
the  movements  in  the  intact  animal  by  the  X-ray  method,  as  in  the 
work  of  Cannon  and  of  Hertz. 

Ludwig  was  the  first  to  call  attention  to  the  fact  that  peristaltic 
waves  are  not  the  only  sort  of  movements  which  occur.  There  is  in 
addition  what  he  termed  pendulum  or  swaying  movements.  In  the 
exposed  intestine  the  propagation  of  the  peristaltic  wave  is  slow 
but  variable;  it  may  be  as  small  as  1  cm.  per  minute.  In  man, 
as  shown  by  X-ray  work,  it  is  more  rapid,  averaging  about  an  inch 
per  minute.  The  pendulum  movements  consist  of  slight  waves  of 
contraction  affecting  both  muscular  coats,  and  these  are  rapidly 
propagated  at  the  rate  of  2  to  5  cms.  per  second.  They  cause  a 
movement  of  the  intestine  from  side  to  side,  and  occur  at  regular 
intervals  of  five  or  six  seconds.  They  are  not  efficacious  in  moving 
the  contents  onwards,  but  they  bring  about  a  mixing  of  the  contents 
very  thoroughly. 

Cannon  observed  by  the  X-ray  method  in  dogs  and  cats  that 
these  pendulum  movements  produce  what  he  calls  "  segmentation." 
A  dark  shadow,  due  to  the  bismuth  in  the  food  administered,  is  at 
one  moment  of  a  certain  length  like  a  short  sausage;  it  then 
constricts  in  the  centre,  and  divides  into  two;  each  half  divides 
again ;  then  the  two  central  segments  join  together,  and  this  repeats 
itself  every  few  seconds.  In  man,  where  the  same  phenomenon  can 
be  seen,  Hertz  timed  the  rate,  and  found  it  occurred  about  ten  times 
in  a  minute  and  a  half.  This  frequent  division  and  subdivision  not 
only  ensures  admixture  with  the  juices,  but  brings  every  portion  in 
turn  in  contact  with  the  absorbing  mucous  membrane,  and  favours 
the  flow  of  chyle  and  blood  in  their  respective  vessels. 

After  a  bismuth  meal,  the  shadow  appears  in  the  caecum  three 
and  a  half  to  five  hours  after  the  food  is  taken.  The  average  time  is 
four  and  a  half  hours.  Assuming  that  it  begins  to  leave  the  stomach 
half  an  hour  after  a  meal,  the  total  journey  along  the  small  intestine 
in  man  occupies  about  four  hours;  the  small  intestine  is  22  J  feet 
long,  so  the  rate  works  out  at  about  an  inch  (a  little  more  than 
2  cms.)  per  minute. 

Nervous  Mechanism. — The  small  intestine,  like  the  stomach,  has  a 
double  nerve  supply. 

(1)  The  Vagus.^  As  in  the  case  of  the  stomach,  these  fibres  are 
accelerator,  and  stimulation  induces  peristaltic  movements.  If  the 
intestine  is  contracting  peristaltically  before  the  stimulus  is  applied, 


CH.  XXXVII.]  INTESTINAL   MOVEMENTS  559 

the  movements  are  inhibited  for  a  brief  period,  after  which  they  are 
greatly  augmented. 

(2)  The  Sympathetic.  These  fibres  leave  the  spinal  cord  by  the 
anterior  roots  from  the  sixth  thoracic  to  the  first  lumbar,  pass 
through  the  lateral  chain,  but  do  not  reach  their  cell-stations  until 
they  arrive  at  the  superior  mesenteric  ganglia :  thence  they  pass  as 
non  -  medullated,  post  -  ganglionic  fibres  to  the  muscular  coats. 
Stimulation  of  these  nerves  causes  inhibition  of  any  peristaltic 
movements  that  may  be  present.  They  also  contain  vaso-motor 
fibres,  and  section  of  these  leads  to  vaso-dilatation  and  a  great 
increase  of  very  watery  succus  entericus. 

These  two  sets  of  nerves  (vagus  and  sympathetic)  terminate  in 
the  ganglionated  plexus  of  Auerbach,  situated  between  the  two 
muscular  layers  of  the  intestinal  wall. 

Under  normal  circumstances,  the  intestinal  movements  are 
regulated  from  the  central  nervous  system  ma  these  two  channels. 
Nevertheless,  after  all  the  nerves  are  cut,  the  movements  continue, 
and  may  remain  normal  for  months.  This  independence  of  control 
from  the  central  nervous  system  justifies  the  use  of  the  term 
autonomic  (see  Chapter  XVIL).  The  true  peristaltic  waves  are, 
however,  coordinated  reflex  actions,  the  centres  for  the  reflex  being 
situated  in  the  ganglion  cells  of  Auerbach's  plexus.  The  movements 
entirely  cease  if  the  intestine  is  painted  with  cocaine,  or  if  nicotine 
is  injected,  for  under  the  influence  of  these  drugs  the  sy  nap  tic  junc- 
tions of  the  ganglion  cells  are  paralysed.  The  importance  of  the 
integrity  of  the  plexus  was  also  shown  by  Magnus  in  his  experiments 
with  strips  of  intestinal  muscle ;  such  strips  are  incapable  of 
spontaneous  rhythm  if  the  nerve  plexus  is  not  removed  with  them. 
Yanasi  found  that  the  intestinal  muscle  of  the  embryo  guinea-pig 
will  contract  when  directly  stimulated,  but  it  is  only  capable  of 
spontaneous  peristalsis  after  the  development  of  Auerbach's 
plexus. 

In  order  that  peristalsis  may  attain  its  object  in  driving  the 
intestinal  contents  onwards,  it  is  necessary  not  only  that  a  wave  of 
contraction  should  travel  along,  but  a  wave  of  relaxation  must  also 
take  place  in  the  front  of  the  mass  which  is  urged  forwards.  This 
does  take  place  on  stimulation ;  the  normal  stimulus  is  the  presence 
of  material  within  the  intestine ;  the  intestine  is  usually  quiescent 
when  empty.  But,  as  Starling  showed,  a  pinch  applied  to  any 
particular  spot  will  cause  a  wave  of  contraction  behind  the  point 
pinched,  and  a  wave  of  relaxation  or  inhibition  in  front  of  it,  which 
travels  downwards. 

Peristalsis  may  be  stimulated  in  many  ways,  and  inhibited  in 
many  ways : — 

(1)  The  usual  stimulus  is  doubtless  the  mechanical  one  of  the 


560  THE   MECHANICAL   PROCESSES   OF   DIGESTION     [CH.  XXXVII. 

presence  of   food-material  in  the  intestine,  and  especially  of  indi- 
gestible food  such  as  cellulose. 

(2)  It  may  be  influenced  by  impulses  from  the  upper  part  of  the 
alimentary  canal ;  the  mere  taking  of  food  will  stimulate  peristalsis 
even  in  the  large  intestine  also.    This  is  most  marked  after  abstinence 
from  food,  and'  the  usual  effect  of  breakfast  as  a  stimulus  for  defeca- 
tion is  a  familiar  example.     The  mere  taking  of  a  glass  of  water 
on  rising  will  in  many  people  have  a  similar  effect. 

(3)  It   may   be   influenced   by   sensations   and   emotions;    thus 
movements  are  inhibited  by  pain,  by  the  exposure  of  the  peritoneum 
to  the  air,  or  by  handling  the  gut  as  in  operations.     Some  emotions, 
such  as  anger,  will  inhibit  peristalsis ;  others  of  a  more  pleasurable 
kind,  leading  to  what  is  popularly  termed  excitement,  will  increase  it 
and  may  even  lead  to  diarrhoea.     It  is  increased  by  muscular  exercise, 
though  here  no  doubt  the  influence  is  partly  the  mechanical  one  of 
the  abdominal  walls  pressing  about  the  intestinal  loops. 

(4)  It  may  be  influenced  by  temperature,  but  here  again  we  have 
most  knowledge  in  regard  to  the  large  intestine;  a  cold  enema  is 
more  efficacious  than  a  warm  one ;  the  latter  is  mainly  sedative. 

(5)  It  may  be  influenced  chemically.     Drugs  given  for  the  relief 
of  diarrhoea  or  constipation  act  in  various  ways;  some  affect  the 
amount  of  secretion,  and  thus  increase  or  decrease  the  fluidity  of  the 
intestinal  contents ;  others  act  on  the  muscular  tissue  or  its  nerves, 
and  so  influence  the  amount  of  peristalsis.     Organic  acids,  including 
the  amino-acids,  produced  during  digestion,  will  increase  peristalsis. 
The  bile  has  a  similar  action,  but  only  on  the  large  intestine ;  various 
oils  act  in  the  same  way ;  certain  gases  do  so  also,  but  here  again  the 
mechanical  effect  of  distension  is  a  factor  to  be  reckoned  with.     A 
vegetable  diet  stimulates  peristalsis,  partly  for  mechanical  reasons — 
the  presence  of  indigestible  cellulose  and  formation  of  gas — partly  for 
a  chemical  reason,  namely,  the  production  of  organic  acids. 

The  pendulum  movements  differ  from  true  peristalsis  in  being 
myogenic ;  that  is,  they  are  due  to  the  rhy thmicality  of  the  muscular 
fibres  themselves,  and  are  propagated  from  one  muscular  fibre  to 
another.  They  are  not  abolished  by  cocaine  or  nicotine.  (Starling.) 

MOVEMENTS  OF  THE  LARGE  INTESTINE. 

We  have  seen  that  in  man  the  food  begins  to  arrive  in  the 
coecuin  four  and  a  half  hours  after  it  reaches  the  stomach ;  when  it 
arrives  in  the  caecum  it  contains  90  per  cent,  of  water,  together  with 
a  small  amount  of  the  unabsorbed  products  of  digestion  of  proteins, 
fats,  and  carbohydrates.  During  its  passage  along  the  large  intestine 
these  are  absorbed,  and  most  absorption  appears  to  occur  in  the 
caecum;  the  normal  firm  consistency  of  the  faeces,  which  contain 


GIL  XXXVII.] 


INTESTINAL   MOVEMENTS 


561 


75  per  cent,  of  water,  is  not  finally  attained  until  they  arrive  in  the 
pelvic  colon,  where  they  are  retained  until  defaecation  takes  place. 

Peristalsis  in  the  colon  occurs  much  more  slowly  than  in  the 
small  intestine,  and  the  accompanying  diagram  gives  the  time  in 
hours  after  the  taking  of  a  bismuth  meal  that  the  shadow  appears  at 
various  points  in  man.  It  reaches  the  hepatic  flexure  of  the  colon 
about  two  hours  after  it  appears  in  the  caecum ;  another  two  hours 
approximately  brings  it  to  the  splenic  flexure  (nine  hours  after  the 
meal).  The  distance  from  the  caecum  to  the  splenic  flexure  is  2 
feet;  the  contents  take  as  long  to  travel  this  distance  as  the 
contents  of  the  small  intestine  take  to  travel  22 J  feet,  that  is,  from 


Hepatic  flexure  - 

Ascending  colon  - 

Cuecum  - 

Pelvic  colon  - 

Pelvis  - 


Splenic  flexure. 


Descending 
colon. 


Umbilicus. 


-\  -  -  Iliac  colon. 


Rectum. 


FIG.  369.— Semi-diagrammatic  view  of  the  large  intestine;  the  figures  give  in  hours  the  average  times 
after  taking  a  meal  that  its  debris  reaches  the  various  parts.  (Hertz.)  This  diagram  shows  the 
transverse  colon  in  a  higher  position  than  it  occupies  when  the  man  is  erect,  and  rather  higher 
than  the  average  even  in  the  horizontal  position. 

the  pylorus  to  the  caecum.  A  further  two  hours  is  occupied  in  the 
journey  along  the  descending  colon,  and  six  hours  more  brings  it  to 
the  end  of  the  pelvic  colon  which  leads  at  an  angle  into  the  rectum. 
The  total  journey  from  the  caecum  to  this  point  occupies  thirteen  and 
a  half  hours.  These  times  were  confirmed  by  auscultation  or  listening 
over  various  parts  of  the  abdomen;  the  gurgling  and  splashing 
sounds  made  by  the  arrival  of  food-material  are  distinctly  audible. 
These  observations  were  made  in  the  daytime ;  during  sleep  the  rate 
of  progress  may  be  slower. 

Some  observers  have  stated  that  retro-peristalsis  occurs  in  the 
colon,  especially  in  its  ascending  portion.     Waves  of  this  kind  would 

2  N 


562  •   Tilt   MECHANICAL  PROCESSES   OF  DIGESTION     [CH.  XXXVII. 

certainly  mix  up  the  csecal  contents  very  thoroughly.  They  have, 
however,  only  been  seen  in  the  exposed  intestine  of  animals,  and 
therefore  may  be  artificially  produced.  A  study  of  X-ray  shadows 
does  not  reveal  their  existence  in  man.  If  retro-peristalsis  does 
occur,  regurgitation  is  effectually  prevented  into  the  small  intestine 
partly  by  the  ileo- csecal  valve,  and  mainly  by  a  strong  band  of 
circular  muscular  fibres  called  the  ileo-caecal  sphincter;  this  is 
normally  kept  in  a  state  of  tonic  contraction  by  impulses  carried  by 
the  splanchnic  nerve ;  it  is  relaxed  when  this  nerve  is  cut,  and  then 
the  contents  of  the  two  intestines  mix  freely.  (T.  E.  Elliott.) 

Defcecation. — The  rectum  is  a  short  tube  about  4  or  5  inches  long 
in  man,  which  is  normally  empty  until  immediately  before  defaeca- 
tion.  In  a  person  of  regular  habits,  a  glass  of  cold  water  on  rising, 
the  stimulus  of  a  cold  bath,  the  taking  of  breakfast,  and  the  after- 
breakfast  pipe  or  cigarette  combine  to  produce  peristalsis  of  the 
colon,  so  that  a  small  quantity  of  faeces  enters  the  rectum,  and  then 
arises  the  desire  to  defaecate.  At  the  end  of  the  rectum  is  the  anal 
canal,  closed  by  a  strong  internal  sphincter  (a  thickening  of  the 
involuntary  circular  fibres  of  the  muscular  coat),  and  by  the  external 
sphincter,  which  is  a  voluntary  muscle  made  of  transversely  striated 
fibres. 

The  "call  to  defecation"  having  been  thus  produced,  the  act 
itself  is  started  by  the  increase  in  intra-abdominal  pressure  brought 
about  by  the  voluntary  contraction  of  the  abdominal  wall,  the 
diaphragm  and  the  levator  ani.  The  diaphragm  is  kept  down  by  deep 
inspirations,  followed  by  closure  of  the  glottis;  this  depresses  the 
colon,  so  that  the  shadow  of  its  transverse  portion  arid  the  flexures 
may  be  lowered  as  much  as  2  inches.  The  transverse  colon  may 
not  rise  to  its  normal  position  until  even  an  hour  has  elapsed 
from  the  act  of  straining  during  defaecation.  Accompanying  the 
action  of  these  voluntary  muscles,  the  whole  colon  from  the  caecum 
onwards  enters  into  powerful  peristalsis;  the  contents  of  the 
transverse  colon  are  thus  forced  into  the  descending  colon,  from 
which  they  are  evacuated  together  with  the  faeces  already  present 
between  the  splenic  flexure  and  the  anus.  The  entrance  of  more 
faeces  into  the  rectum  until  they  reach  the  anal  canal  irritates  afferent 
nerves  in  the  wall  of  the  rectum ;  the  nerve  impulses  so  generated 
pass  to  a  centre  or  centres  in  the  lumbo-sacral  region  of  the  spinal 
cord,  where  efferent  impulses  are  set  in  action  upon  which  depend 
the  reflex  acts  required  to  complete  the  process ;  these  are  :— 

1.  Strong  peristalsis  of  the  whole  colon. 

2.  Continued  contraction  of  the  abdominal  muscles. 

3.  Eelaxation  of  both  the  anal  sphincters  and  of  the  levator  ani. 
The  last  traces  of  faeces  are  expelled  by  voluntary  contractions  of 

the  levator  ani. 


CH.  XXXVII.]      NERVOUS   MECHANISM   OF  LARGE   INTESTINE  563 

If  the  bowels  are  opened  once  a  day,  the  interval  between  a 
meal  and  the  evacuation  of  its  residue  varies  between  nine  and  thirty- 
two  hours,  the  time  depending  on  the  hours  of  meals  and  that  of 
defaecation.  Food  taken  less  than  nine  hours  previously  would  not 
have  reached  far  enough. 

If  the  call  to  defaecation  is  resisted,  the  desire  soon  passes  away, 
and  may  not  recur  until  the  next  regular  period  arrives  for  the 
opening  of  the  bowels,  twenty-four  hours  later.  During  this  time 
the  rectum  contains  faeces,  there  being  no  retro-peristalsis  to  carry 
them  back  into  the  colon.  This  is  one  of  the  commonest  causes  of 
constipation,  for  the  retained  faeces  continue  to  lose  water,  and  get 
harder,  and  more  difficult  to  expel. 

Nervous  Mechanism. — The  large  intestine  resembles  the  rest  of 
the  alimentary  canal  in  having  a  double  nerve  supply. 

(1)  The  sympathetic.     These  fibres  leave  the  cord  by  the  lower 
lumbar  anterior  roots;   these   pass  through  the  lateral   chain,  and 
reach  their  cell-stations  in  the  inferior  mesenteric  ganglion ;  the  post- 
ganglionic  fibres  arising  there,  pass  by   the  colonic  nerves  to   the 
colon,  and  by  the  hypogastric  nerve  to  the  rectum  and  internal  anal 
sphincter. 

(2)  The   nervus   erigens.     This   takes   the   place  of   the  vagus, 
which  forms  the  second  source  of  nerve  supply  to  the  stomach  and 
small  intestine.      This   nerve  is   excitatory   to   both   coats   of  the 
muscular  wall,  whereas  the  sympathetic  is  inhibitory  to  the  internal 
sphincter. 

The  fibres  which  pass  to  the  rectum  by  the  pelvic  nerves  or  nervi 
erigentes  arise  from  the  third  sacral  nerve,  and  have  their  cell- 
stations  in  the  haemorrhoidal  nerve  plexus,  which  is  the  name  given 
to  this  portion  of  the  plexus  of  Auerbach. 

The  voluntary  muscles,  namely,  the  external  anal  sphincter  and 
the  levator  ani,  are  supplied  by  the  fourth  sacral  nerve,  which  arises 
from  nerve-cells  in  the  conus  terminalis  of  the  spinal  cord. 

If  Starling's  experiment  of  pinching  a  spot  in  the  large  intestine 
is  performed,  much  the  same  result  follows  as  in  the  small  intestine ; 
the  wave  of  inhibition  which  travels  downwards  is  well  seen,  but  the 
upward  wave  of  contraction  is  not  so  marked  as  in  the  small  intestine. 
Stimulation  of  the  sympathetic  (hypogastric)  nerve-fibres  produces 
movements  of  the  colon  and  rectum,  and  inhibition  of  the  internal 
sphincter ;  that  is  the  main  phenomenon  in  the  act  of  defaecation.  If 
the  lower  part  of  the  spinal  cord  is  destroyed,  defaecation  still  occurs, 
but  it  is  an  unconscious  act,  and  the  reflex  is  imperfectly  executed ; 
the  hypogastric  part  of  the  mechanism  is  intact,  and  probably  the 
reflex  centre  concerned  is,  as  in  the  small  intestine,  in  the  peripheral 
ganglia  of  Auerbach's  plexus ;  but  the  destruction  of  the  conus 
terminalis  prevents  the  normal  reflexes  taking  place  in  which  the 


564  THE  MECHANICAL  PROCESSES   OF  DIGESTION    [CH.  XXXVII. 

levator  ani  and  external  sphincter  are  concerned,  and  the  paralysis 
of  these  voluntary  muscles  may  lead  to  incontinence  of  faeces. 

We  thus  see  that  the  lowermost  portion  of  the  alimentary  canal 
resembles  its  uppermost  portion  (pharynx  and  oesophagus)  in  being 
more  under  external  nervous  control  than  is  the  small  intestine. 
Autonomy  at  the  rectal  and  anal  portion  is  for  obvious  reasons  unde- 
sirable. 


CHAPTEE   XXXVIII 


THE   URINARY  APPARATUS 

THIS  consists  of  the  kidneys ;  from  each  a  tube  called  the  ureter  leads 
to  the  bladder,  in  which  the  urine  is  temporarily  stored ;  from  the 
bladder  a  duct  called  the  urethra 
leads  to  the  exterior. 

The  Kidneys  are  situated  in  the 
lumbar  region  of  the  abdomen  on 
either  side  of  the  spinal  column 
behind  the  peritoneum.  In  man  each 
is  about  4  inches  long,  and  weighs 
about  4J  oz. 

Structure. — The  kidney  is  covered 
by  a  fibrous  capsule,  which  is  slightly 
attached  at  its  inner  surface  to  the 
proper  substance  of  the  organ  by 
means  of  very  fine  bundles  of  areolar 
tissue  and  minute  blood  -  vessels. 
At  the  hilus  of  the  kidney  it  becomes 
continuous  with  the  external  coat  of 
the  upper  and  dilated  part  of  the 
ureter  (fig.  370). 

On  dividing  the  kidney  into  two 
equal  parts  by  a  section  carried 
through  its  long  convex  border,  it  is 
seen  to  be  composed  of  two  portions, 
called  respectively  cortical  and  medul- 
lary ;  the  latter  is  composed  of  about 
a  dozen  conical  bundles  of  urinary 
tubules,  each  bundle  forming  what  is  called  a  pyramid.  The  upper 
part  of  the  ureter  is  dilated  into  the  pelvis ;  and  this,  again,  after 
separating  into  two  or  three  principal  divisions,  is  finally  subdivided 
into  still  smaller  portions,  varying  in  number  from  about  8  to  12, 
called  calyces.  Each  of  these  little  calyces  or  cups  receives  the 
pointed  extremity  or  papilla  of  a  pyramid.  The  number  of  pyramids 
varies  in  different  animals ;  in  some  there  is  only  one. 

The  kidney  is  a  compound  tubular  gland,  and  both  its  cortical 
and  medullary  portions  are  composed  of  tubes,  the  tubuli  uriniferi, 
which,  by  one  extremity,  in  the  cortical  portion,  commence  around 

565 


FIG.  370.— Kan  of  a  longitudinal  section 
through  the  pelvis  and  substance  of  the 
right  kidney,  §  :  a,  the  cortical  sub- 
stance ;  I,  b,  broad  part  of  the  pyramids 
of  Malpighi ;  c,  c,  the  divisions  of  the 
pelvis  named  calyces,  laid  open  ;  c\  one 
of  those  unopened ;  d,  summit  of  the 
pyramid  projecting  into  calyces ;  c,  e, 
section  of  the  narrow  part  of  two 
pyramids  near  the  calyces ;  p,  pelvis 
or  enlarged  portion  of  the  ureter 
within  the  kidney ;  u,  the  ureter  ;  s,  the 
sinus  ;  h,  the  hilus. 


566  THE  URINARY  APPARATUS  [CH.  XXXVIII. 

tufts  of  capillary  blood-vessels,  called  Malpighian  bodies,  and,  by  the 
other,  open  through  the  papillae  into  the  pelvis  of  the  ureter,  and 


Pro.  3d.— A  diagram  of  the  uriniferous  tubes.  A,  cortex  limited  externally  by  the  capsule; 
o,  subcapsular  layer  not  containing  Malpighian  corpuscles ;  a',  inner  stratum  of  cortex,  also  without 
Malpighian  capsules  ;  B,  boundary  layer;  C,  medullary  part  next  the  boundary  layer;  1,  Bowman's 
capsule  of  Malpighian  corpuscle ;  2,  neck  of  capsule;  3,  first  convoluted  tubule;  4,  spiral  tubule; 
5,  descending  limb  of  Henle's  loop  ;  6,  the  loop  proper ;  7,  thick  part  of  the  ascending  limb  ;  8,  spiral 
part  of  ascending  limb  ;  9,  narrow  ascending  limb  in  the  medullary  ray ;  10,  the  zigzag  tubule  ;  11, 
the  second  convoluted  tubule ;  12,  the  junctional  tubule  ;  13,  the  collecting  tubule  of  the  medullary 
ray  ;  14,  the  collecting  tube  of  the  boundary  layer ;  15,  duct  of  Bellini.  (Klein.) 

thus  discharge  the  urine  which  flows  through  them.     They  are  bound 
together  by  connective  tissue. 


CH.  XXXVIII.]  THE   KIDNEY   TUBULES  567 

In  the  pyramids  the  tubes  are  straight — uniting  to  form  larger 
tubes  as  they  descend  through  these  from  the  cortical  portion;, 
while  in  the  latter  region  they  are  convoluted.  But  in  the  boundary 
zone  between  cortex  and  medulla,  small  collections  of  straight  tubes 
called  medullary  rays  project  into  the  cortical  region. 

Each  begins  in  the  cortex  as  a  dilatation,  called  the  Capsule  of 
Bowman  ;  this  encloses  a  tuft  or  glomerulus  of  capillaries,  called  a 
Malpighian  corpuscle.  The  tubule  leaves  the  capsule  by  a  neck,  and 


FIG.  372. — Malpighian  corpuscle,  injected  through  the  renal  artery  with  coloured  gelatin  ;  a,  glomerular 
vessels ;  b,  c,  capsule  of  Bowman ;  (/,  afferent  vessel  of  glomerulus ;  e,  efferent  vessels ; 
/,  epithelium  of  tubes.  (Cadiat.) 

then  becomes  convoluted  (first  convoluted  tubule),  but  soon  after 
becomes  nearly  straight  or  slightly  spiral  (spiral  tubule) ;  then  rapidly 
narrowing,  it  passes  down  into  the  medulla  as  the  descending  tubule  of 
Henle ;  this  turns  round,  forming  a  loop  (loop  of  Henle),  and  passes 
up  to  the  cortex  again  as  the  ascending  tubule  of  Henle.  It  then 
becomes  larger  and  irregularly  zigzag  (zigzag  tubule)  and  again  con- 
voluted (second  convoluted  tubule).  Eventually  it  narrows  into  a 
junctional  tubule,  which  joins  a  straight  or  collecting  tubule.  This 
passes  straight  through  the  medulla,  where  it  joins  with  others  to 
form  one  of  the  ducts  of  Bellini  that  open  at  the  apex  of  the  pyramid. 
These  parts  are  all  shown  in  fig.  371. 

In  the  capsule,  the  epithelium  is  flattened  and  reflected  over  the 
glomerulus, 


568 


THE    URINARY   APPARATUS 


[CH.  XXXVI TI. 


In  the  neck  the  epithelium  is  still  flattened,  but  in  some  animals, 
such  as  frogs,  where  the  neck  is  longer,  the  epithelium  is  ciliated. 

In  the  first  convoluted  and  spiral  tubules,  it  is  thick,  and  the  cells 
show  a  fibrillated  structure,  except  around  the  nucleus,  where  the 
protoplasm  is  granular.  The  cells  interlock  laterally  and  are  difficult 
to  isolate.  In  the  narrow  descending  tubule  of  Henle  and  in  the 
loop  itself,  the  cells  are  clear  and  flattened  and  leave  a  considerable 
lumen;  in  the  ascending  limb  they  again  become  striated  and 
nearly  fill  the  tubule.  In  the  zigzag  and  second  convoluted  tubules 
the  fibrillations  become  even  more  marked.  The  functional  tubule 
has  a  large  lumen,  and  is  lined  by  clear  flattened  cells;  the  col- 
lecting tubules  and  ducts'  of  Bellini  are  lined  by  clear  cubical  or 
columnar  cells  (see  fig.  373). 


a 


nn  ?h7  •  T?  a  VemLcal  secj;lon  through  the  kidney  of  a  dog-the  capsule  of  which  is  supposed  to  be 
on  we  right,  a,  The  capillaries  of  the  Malpighian  corpuscle,  which  are  arranged  in  lobules  ;  n,  neck 
of  capsule  ;  c,  convoluted  tubes  cut  in  various  directions;  6,  zigzag  tubule;  d,  e,  and/,  are  straight 
?m  ^SdlawJ'^)80*1^  tUbe;  e'sP»^  tube; /.narrow  section  of  ascending  limb. 

The  extent  of  the  zone  of  clear  cells  in  the  loop  of  Henle  varies 
a  good  deal  in  different  animals ;  a  diminution  of  this  part  of  the 
tubule  lessens  the  length  of  the  total  loop ;  in  most  animals  there 
is  an  admixture  of  long  and  short  loops,  though  the  proportion  of  the 
two  varies  greatly  in  different  parts  of  the  animal  kingdom. 


CH.  XXXVIII.] 


THE   KIDNEY   TUBULES 


569 


Blood-vessels  of  Kidney. — The  renal  artery  enters  the  kidney 
at  the  hilus,  and  divides  into  branches  that  pass  towards  the  cortex, 

then  turn  over  and  form  in- 
complete  arches  in  the  region 
between  cortex  and  medulla. 
From  these  arches  vessels  pass 

to  the  surface  which  are  called 
the  interldbular  arteries;  they 

give  off  vessels  at  right  angles, 


FIG.  375.—  Diagram  showing  the  relation 
of  the  Malpighian  body  to  the  urin- 
iferous  ducts  and  blood-vessels. 
«,  One  of  the  interlobular  arteries  ; 
a',  afferent  artery  passing  into  the 
glomerulus  ;  c,  capsule  of  the  Mal- 
pighian body,  forming  the  com- 
mencement of  and  continuous  with 
the  uriniferous  tube;  e','.e',  -efferent 
vessels  which  subdivide  and  form  a 
plexus,  p,  surrounding  the  tube,  and 
finally  terminate  in  the  branch  of 
the  renal  vein  e.  (After  Bowman.) 

which  are  the  afferent  vessels  of 
the  glomeruli  ;  a  glomerulus  is 
made  up  of  capillaries  as  pre- 
viously stated.  From  each  a 
smaller  vessel  (the  efferent  vessel 
of  the  glomerulus)  passes  out,  and 

like    a    portal    V6SSel   On    a    Small 

i       v        i  • 

Scale,  DreaKS   Up    OnC6    more  into 

capillaries  which  ramify  between 
the  convoluted  tubules.  These 
unite  to  form  veins  (interldbular 
veins)  which  accompany  the  interlobular  arteries  ;  they  pass  to  venous 
arches,  parallel  to,  but  more  complete  than,  the  corresponding  arterial 
arches  ;  they  ultimately  unite  to  form  the  renal  vein  that  leaves  the 
hilus.  These  veins  receive  also  others  which  have  a  stellate  arrange- 
ment near  the  capsule  (vence  stellulce). 


Pin.  374.  -Vascular  supply  of  kidney,  a,  Part  of 
arterial  arch  ;  b,  interlobular  artery  ;  c,  glo- 
merulus;  d,  efferent  vessel  passing  to  the 


inter- 


570  THE   URINARY   APPARATUS  [CH.  XXXVIII. 

The  medulla  is  supplied  by  pencils  of  fine  straight  arterioles 
which  arise  from  the  arterial  arches.  They  are  called  arterice  rectce. 
The  efferent  vessels  of  the  glomeruli  nearest  the  medulla  may 
also  break  up  into  similar  vessels  which  are  called  false  arterice 
rectce.  The  veins  (pence  rectce)  take  a  similar  course  and  empty  them- 
selves into  the  venous  arches.  In  the  boundary  zone  groups  of  vasa 
recta  alternate  with  groups  of  tubules,  and  give  it  a  striated 
appearance. 

The  Ureters. — The  duct  of  each  kidney,  or  ureter,  is  a  .Jmbe 
about  the  size  of  a  goose-quill,  and  from  twelve  to  sixteen  inches 
in  length,  which,  continuous  above  with  the  pelvis,  ends  below  by 
perforating  obliquely  the  walls  of  the  bladder,  and  opening  on  its 
internal  surface. 

It  is  constructed  of  three  coats :  (a)  an  outer  fibrous  coat ;  (b)  a 
middle  muscular  coat;  and  (c)  a  mucous  membrane  continuous  with 
that  of  the  pelvis  above,  and  of  the  urinary  bladder  below ;  it  is 
composed  of  areolar  tissue  lined  by  transitional  epithelium. 

The  Urinary  Bladder  is  pyriform;  its  widest  part,  which  is 
situate  above  and  behind,  is  termed  the  fundus ;  and  the  narrow 
constricted  portion,  by  which  it  becomes  continuous  with  the  urethra, 
is  called  its  cervix  or  neck. 

It  is  constructed  of  four  coats, — serous,  muscular,  areolar  or 
submucous,  and  mucous.  The  circular  muscular  fibres  are  especially 
developed  around  the  cervix  of  the  organ  and  form  the  sphincter 
vesicce.  The  mucous  membrane  is  like  that  of  the  ureters.  It  is 
provided  with  mucous  glands,  which  are  most  numerous  near  the 
neck  of  the  bladder. 

The  bladder  is  well  provided  with  blood-  and  lymph-vessels,  and 
with  nerves.  The  latter  consist  of  branches  from  the  sacral  and 
hypogastric  plexuses.  Ganglion  cells  are  found,  here  and  there,  on 
the  course  of  the  nerve-fibres. 

The  Urethra. — This  occupies  the  centre  of  the  corpus  spongiosum 
in  the  male.  As  it  passes  through  the  prostate  it  is  lined  by  transi- 
tional, but  elsewhere  by  columnar  epithelium,  except  near  the  orifice, 
where  the  epithelium  is  stratified  like  the  epidermis,  with  which  it 
becomes  continuous.  The  female  urethra  has  stratified  epithelium 
throughout.  The  epithelium  rests  on  a  vascular  corium,  and  this  is 
severed  by  submucous  tissue  containing  an  inner  longitudinal  and 
an  outer  circular  muscular  layer.  Outside  this  a  plexus  of  veins 
passes  insensibly  into  the  surrounding  erectile  tissue. 

Into  the  urethra  open  a  number  of  oblique  recesses  or  lacunce,  a 
number  of  small  mucous  glands  (glands  of  Littre"),  two  compound 
racemose  glands  (Cowper's  glands),  the  glands  of  the  prostate,  and 
the  vas  deferens.  The  prostate,  which  surrounds  the  commencement 
of  the  male  urethra,  is  a  muscular  and  glandular  mass.  Its  glands 


CH.  XXXVIII.]  THE   KIDNEY  ONCOMETER  571 

are  tubular  and  lined  by  columnar  epithelium;  their  secretion 
dilutes  the  semen.  Very  little  is  known  of  the  function  of  the 
prostate;  it  often  enlarges  and  becomes  calcareous  in  old  age,  and 
gives  rise  to  discomfort  and  difficulty  in  micturition.  Its  removal 
under  these  circumstances  is  a  most  beneficial  operation. 

The  Nerves  of  the  Kidney. 

These  are  derived  from  the  renal  plexus  of  each  side.  The  renal 
plexus  consists  of  both  medullated  and  non-medullated  nerve-fibres, 
with  collections  of  ganglion  cells.  Fibres  from  the  anterior  roots  of 
the  eleventh,  twelfth,  and  thirteenth  dorsal  nerves  (in  the  dog)  pass 
into  this  plexus.  They  are  both  vaso-constrictor  and  vaso-dilator  in 
function.  The  nerve- cells  on  the  course  of  the  constrictor  fibres  are 
situated  in  the  coeliac,  mesenteric,  and  renal  ganglia;  the  nerve-cells 
on  the  course  of  the  dilator  fibres  are  placed  in  the  solar  plexus  and 
renal  ganglia.  We  have,  at  present,  no  knowledge  of  true  secretory 
nerves  to  the  kidney,  and  the  amount  of  urine  is  influenced,  to  a 
certain  extent  at  any  rate,  by  the  blood-pressure  in  its  capillaries. 
We  shall,  a  few  pages  hence,  however,  see  that  the  amount  of  urine 
does  not  depend  wholly  on  the  height  of  the  blood-pressure ;  and  one 
very  striking  fact  in  this  relation  may  be  mentioned  now, — namely, 
that  if  the  blood-pressure  is  increased  without  allowing  the  blood  to 
flow,  the  amount  of  urine  formed  is  not  increased ;  this  can  be  done 
by  ligaturing  the  renal  vein ;  the  blood-pressure  within  the  kidney 
then  rises  enormously,  but  the  flow  of  urine  stops. 

The  Kidney  Oncometer. 

This  is  an  instrument  constructed  on  plethysmographic  principles, 
by  means  of  which  the  volume  of  the  kidney  is  registered.  The 
general  characters  of  this  instrument  are  described  in  the  diagrams 
on  p.  310.  The  special  form  introduced  by  Eoy  for  the  kidney  is 
shown  in  fig.  376.  Eoy's  instrument,  however,  is  but  seldom  used  at 
the  present  day.  An  air  oncometer,  connected  with  a  Marey's 
tambour  or  a  bellows  recorder  (like  that  figured  for  the  spleen  on 
p.  311),  is  much  less  complicated,  and  gives  better  results. 

It  is  found  that  the  effect  on  the  volume  of  the  organ  of  dividing 
or  stimulating  nerves  corresponds  to  blood-pressure.  If  a  rise  of 
pressure  in  the  renal  artery  is  produced  by  constriction  of  the  renal 
arterioles,  this  is  accompanied  by  a  fall  of  pressure  in  the  renal 
capillaries  and  a  shrinkage  of  the  kidney.  Increase  in  the  volume 
of  the  kidney  is  produced  by  the  opposite  circumstances. 

The  accompanying  tracing  (fig.  377)  shows  that  in  a  normal 
oncometric  curve  from  the  kidney  there  is  a  rise  of  volume,  due  to 


572 


THE   URINARY  APPARATUS 


[CH.  XXXYI1I. 


each  heart-beat,  and  larger  waves,  which  accompany  respiration.     In 
some  cases  larger  sweeping  waves  (Mayer  curves)  are  seen  as  well, 


FIG.  37(3. — Oncometers  for 


but   they   are    absent   in    the   tracing    reproduced :    if,   in   such   a 
tracing,  the  kidney  curve  is  compared  with  the  tracing  of  arterial 


FIG.  377.-  -Curve  taken  by  renal  oncometer  compared  with  that  of  ordinary  blood-pressure,    cr,  Blood- 
pressure  curve ;  b,  kidney  curve.    (Roy.) 

pressure,  it  will  be  seen  that  the  rise  of  pressure  is  simultaneous  with 
the  fall  in  kidney  volume  due  to  constriction  of  the  renal  vessels. 


The  Functions  of  the  Kidney. 

The  function  of  the  kidneys  is  to  separate  the  urinary  con- 
stituents from  the  blood,  and  by  this  means  the  blood  is  maintained 
of  constant  composition.  The  kidrfey  cells  are  remarkably  sensitive, 
so  that  alterations  in  the  composition  of  the  Blood  which  are  too 
slight  to  be  detected  by  chemical  analysis  (such  as  an  increase  of 
water  or  of  chlorides  after  a  meal)  are  felt  by  the  kidney,  and 
increased  secretion  (diuresis)  occurs.  In  the  case  of  some  urinary 
constituents,  they  are  practically  entirely  removed  by  the  kidney ; 
urea  is  an  example  of  this  class.  In  other  cases  excess  beyond  a 


CH.  XXXVin.]  FUNCTIONS   OF  THE   KIDNEY  573 

certain  percentage  is  removed  from  the  blood ;  sodium  chloride  is  an 
instance  of  these. 

Although  the  glandular  epithelium  of  the  convoluted  tubes  is 
par  excellence  the  secreting  mechanism  of  the  kidney,  much  difference 
of  opinion  exists  as  to  the  part  played  by  each  of  the  several  units  in 
the  histological  complex  we  have  already  described,  and  this  is 
especially  the  case  in  relation  to  that  unique  structure,  the  glomerulus. 
We  have  seen  that  the  efferent  vessel  of  each  glomerulus  has  a 
smaller  calibre  than  the  afferent  vessel,  and  this  produces  high 
pressure  in  the  glomerular  capillaries.  The  efferent  vessel,  more- 
over, resembles  an  arteriole  in  its  abundance  of  muscular  tissue,  and 
this  maintains  the  high  in tra- glomerular  blood  -  pressure.  This 
arrangement  led  Ludwig  to  the  conception  that  the  glomerulus  is  a 
filter,  and  the  filter  theory  has  formed  the  basis  of  much  subsequent 
work,  and  numerous  theories. 

It  is  impossible  in  a  question  upon  which  physiologists  are  so 
divided,  to  make  a  complete  statement  of  the  case  which  will  meet 
with  universal  acceptance,  and  still  more  difficult  is  it  to  build  any 
sure  system  of  medical  treatment  upon  so  insecure  a  foundation; 
and  before  we  attempt  to  consider  the  function  of  this  or  that  type 
of  cell  in  the  kidney,  let  us  see  what  can  be  laid  down  in  relation  to 
the  physiology  of  the  kidney  as  a  whole. 

We  may  sum  up  the  process  of  urinary  secretion  as  follows : — 
One  fluid,  the  arterial  blood,  enters  the  kidney ;  two  fluids,  the 
venous  blood  and  the  urine,  leave  it.  Both  of  these  fluids  are 
different  in  composition  from  the  arterial  blood.  The  following 
table  gives  the  approximate  values  of  the  principal  constituents  in 
the  plasma  of  the  arterial  blood,  and  in  the  urine : — 

Arterial  Blood-plasma.  Urine. 

Total  solids       .  .  10  per  cent.  4      per  cent. 

Proteins   .  .  7 '5  to  8    „       „  0 

Sodium  chloride  .  0'8      ,,       ,,  1'2 

Urea         .         .  .  0'03    „       „  2*0 

Sugar        .  .  0-15    „„  0 

Uric  acid .         .  .  traces  0  '05 


Hippuric  acid 


0         „       „  0'07 


We  know  that  it  is  not  possible  to  convert  any  fluid  into  two 
others,  each  of  different  composition  from  itself,  without  an  ex- 
penditure of  energy  which  must  come  from  somewhere  outside  the 
fluids  themselves.  In  the  case  of  the  kidney,  as  in  other  secreting 
glands,  this  energy  comes  from  the  cells  of  the  organ. 

The  secretion  of  urine  is  therefore  the  result  of  work  done  by  the 
kidney.  The  quantity  of  this  work  may  be  measured  within  certain 
limits,  and  the  energy  transformed  by  the  kidney  may  be  estimated  in 
more  than  one  way.  The  urine  is  much  more  concentrated,  as  regards 


574  THE  URINAKY  APPARATUS  [CH.  XXXVIII. 

crystalline  constituents,  than  the  plasma  from  which  it  was  produced. 
Thus,  urine  contains  about  2  per  cent,  of  urea  on  an  average,  plasma 
0'03  per  cent.,  and  ths  same  is  true  in  different  degrees  for  other  sub- 
stances. It  follows  that  if  urine  were  placed  inside  an  osmometer  and 
an  unlimited  supply  of  plasma  outside,  water  would  be  sucked  into 
the  osmometer  until  a  column  of  fluid  of  great  height  had  been 
established  and  much  work  had  been  performed  in  raising  it.  In  a 
specific  instance,  the  blood-plasma  had  an  osmotic  pressure  equivalent 
to  a  0'92  per  cent,  solution,  and  the  urine  to  a  4  per  cent,  solution,  of 
sodium  chloride.  From  these  data,  and  from  the  amount  of  urine 
secreted,  it  is  possible  to  make  a  calculation  of  the  work  performed 
by  the  kidney.  In  other  words,  the  energy  used  by  the  kidney  in 
secreting  the  urine  cannot  be  less  than  what  is  given  by  this  purely 
physical  consideration. 

The  maximum  energy  used  up  by  the  kidney  may  be  calculated 
in  quite  another  way.  Estimations  have  been  made  of  the  amount 
of  oxygen  used  by  the  kidney  in  secreting  urines  of  known  concen- 
tration ;  this  oxygen  may  be  taken  as  a  measure  of  the  amount  of 
kidney  material  used  up.  If  the  amount  of  metabolism  be  thus 
determined,  we  can  arrive  at  the  amount  of  energy  used  up  by  a 
knowledge  of  the  heat  produced  by  the  decomposition  of  this  amount 
of  kidney  material. 

The  kidney  cannot  be  doing  more  work  than  its  metabolism  accounts  for.  If 
we  suppose  the  kidney  living  on  protein  (and  the  figures  would  not  differ  greatly  if 
we  supposed  it  to  be  living  on  carbohydrate),  we  may  start  with  the  following 
constants:  1  c.c.  of  oxygen  oxidises  1  milligramme  of  protein,  and  forms  water, 
carbon  dioxide,  urea,  etc.  In  doing  so,  it  gives  out  4000  small  calories  (see 
Chapter  XLIL),  and  this  is  equivalent  to  170,000  gramme-centimetres  of  work.  In 
a  typical  experiment  during  diuresis,  the  kidney  used  4  c.c.  of  oxygen  per  minute  ; 
this  was,  therefore,  equivalent  to  680,000  gramme-centimetres  of  work,  and  the 
energy  transformed  from  potential  to  kinetic  energy  by  the  kidney  cannot  have 
been  less  than  this.  Let  us  consider  what  evidence  there  is  of  mechanical  work 
which  the  organ  does  as  an  offset  against  this;  one  way  in  which  the  work 
manifests  itself  is  in  the  concentration  of  the  urine ;  this  fluid  is  many  times  more 
concentrated  than  the  blood-plasma.  The  degree  of  concentration  can  be  calcu- 
lated from  a  knowledge  of  the  freezing-points  of  the  blood  and  urine ;  the  greater 
the  concentration  of  a  solution  of  a  crystalline  substance,  the  lower  is  its  freezing- 
point  (see  p.  326).  In  this  way,  it  was  calculated  that  14,700  gramme-centimetres  of 
work  was  done  in  the  case  just  referred  to.  If  the  calculation  is  made  for  each 
salt  separately,  a  much  higher  figure  than  this  would,  however,  be  obtained. 

The  practical  importance  of  these  considerations  to  the  physician 
lies  in  the  fact  that  the  expenditure  of  energy  involves  combustion, 
and  combustion  demands  oxygen.  For  this  reason,  if  for  no  other, 
an  efficient  supply  of  oxygen,  that  is,  an  efficient  circulation  of  blood, 
is  the  first  condition  necessary  to  a  healthy  kidney.  Eenal  trouble 
is  often  secondary  to  cardiac  trouble,  and  may  be  the  result  of 
accumulation  of  blood  in  the  great  veins ;  in  such  cases  it  is  obvious 
that  the  renal  trouble  cannot  be  overcome  by  treating  the  kidney, 


CTT.  XXXVIII.]       URINARY   SECRETION   AND   BLOOD-PRESSURE 


575 


but  the  cardiac  difficulty  must  be  dealt  with.  Again,  the  physician 
may  endeavour,  with  a  certain  measure  of  success,  to  decrease  the 
work  which  falls  upon  the  kidney,  by  transferring  the  excretory 
function  as  far  as  possible  to  the  skin.  This  may  be  accomplished 
by  stimulating  the  skin  to  action  by  hot  air  baths,  or  even  more 
successfully  by  ordering  the  patient  to  a  hot  dry  climate. 

The  importance  of  changes  in  the  circulation  is  still  further 
accentuated  by  the  fact  that  the  arterial  pressure  appears  to  exercise 
a  direct  effect  upon  the  volume  of  urine  secreted  by  the  kidney.  In 
a  general  sense,  those  forms  of  experimental  procedure  which  increase 
the  volume  of  the  kidney,  as  measured  by  the  oncometer,  increase 
also  the  flow  of  urine.  This  is  illustrated  by  the  data  given  in  the 
following  table :— 


Procedure. 

General  blood- 
pressure. 

ll^ual  vessels. 

Kidney  volume. 

Urinary  lluw. 

Division  of  spinal  cord  in 
neck 

Falls  to 
40  mm. 

Relaxed 

Shrinks 

Ceases 

Stimulation  of  cord  . 

Rises 

Constricted 

Shrinks 

Diminished 

Stimulation  of  cord  after 
section  of  renal  nerves 

Rises 

Passively 
dilated 

Swells 

Increased 

Stimulation       of       renal 

Unaffected 

Constricted 

Shrinks 

Diminished 

nerves 

Stimulation  of  splanchnic 
nerve 

Rises 

Constricted 

Shrinks 

Diminished 

Plethora    .... 

Rises 

Dilated 

Swells 

Increased 

Haemorrhage    . 

Falls 

Constricted 

Shrinks 

Diminished 

Kesults  obtained  by  the  oncometer  are  less  easy  to  interpret  in 
tlfe  kidney  than  in  other  organs,  because  of  the  complexity  of  its 
vascular  mechanism.  For  example,  constriction  of  the  efferent 
vessels  of  the  glomeruli  might  raise  the  pressure  in  the  glomerular 
capillaries,  and  simultaneously  lower  the  pressure  in  other  parts  of 
the  kidney,  and  the  net  result  would  be  no  material  alteration  in  the 
volume  of  the  whole  kidney.  The  oncometric  record  is  also  com- 
plicated by  the  consideration  that  when  diuresis  is  established  an 
increase  in  the  volume  of  the  kidney  may  not  be  wholly  of  vascular 
origin,  but  may  be  partly  due  to  accumulation  of  urine. 

In  spite  of  these  difficulties,  we  are  nevertheless  justified  in 
concluding  that  pronounced  changes  in  the  size  of  the  kidney  are  of 


576  THE   URINARY  APPARATUS  [CH.  XXXVIII. 

vascular  origin,  and  they  furnish  the  best  index  we  have  of  the 
pressure  of  the  blood  in  the  capillaries.  They  give  no  indication  of 
the  rate  of  blood-flow  through  the  organ,  which  is  an  altogether 
different  thing. 

Finally,  from  the  medical  point  of  view,  the  activity  of  the 
kidney  may  be  invoked  by  the  administration  of  drugs.  Such  drugs 
are  called  diuretics.  They  act  in  different  ways,  some  locally  on  the 
kidney,  such  as  caffeine,  and  certain  saline  diuretics ;  others,  such 
as  digitalis,  act  upon  the  general  blood-pressure.  It  is  important,  in 
prescribing  these  drugs,  not  to  lose  sight  of  the  fact  that  whilst  the 
greatest  benefit  may  attend  their  action,  it  is  doubtful  whether  any 
of  those  commonly  administered  through  the  alimentary  canal  (the 
digitalis  group  excepted)  can  be  regarded  as  doing  their  work  without 
throwing  a  greater  or  less  strain  upon  some  portion  of  the  renal 
epithelium. 

Having  in  this  way  considered  the  kidney  as  a  whole,  we  must 
next  consider  the  function  of  the  different  types  of  cell  found  in  the 
kidney  tubule,  including  the  capsule  of  Bowman  in  that  expression. 

A  complete  statement  of  the  case  would  involve  for  each  type  a 
description  of  (1)  which  of  the  urinary  constituents  traverses  its 
protoplasm;  (2)  the  mechanism,  whether  secretory  or  physical 
diffusion  or  filtration,  by  which  the  constituent  is  propelled ;  and 
(3)  the  direction  in  which  it  goes,  whether  from  the  blood  to  the 
urine,  or  from  the  urine  to  the  blood. 

Fortunately,  however,  it  is  not  necessary  to  discuss  the  matter  quite 
so  exhaustively,  for  certain  possibilities  have  never  been  advanced, 
and  so  can  be  put  upon  one  side.  For  instance,  no  one  has  ever 
suggested  that  the  thick  glandular  cells  of  the  tubules  allow  materials 
to  pass  through  them  by  physical  diffusion;  here,  undoubtedly,  we 
have  to  deal  with  secretory  action  alone.  Again,  the  direction  of 
flow  through  the  capsule  of  Bowman  is  undoubtedly  from  the  blood 
to  the  urine,  and  the  passage  of  water  in  the  opposite  direction,  if  it 
does  occur  at  all,  is  limited  to  certain  regions  of  the  tubule  itself. 

Our  problem,  therefore,  is  simplified,  and  the  questions  remaining 
are  (1)  whether  the  flow  in  the  glomeruli  is  due  to  physical  or  to 
physiological  (secretory)  processes;  (2)  the  evidence  of  secretory 
action  in  the  tubules ;  and  (3)  the  question  whether  reabsorption  of 
fluid  occurs  in  the  tubules.  In  relation  to  the  first  of  these  points 
we  may  ask  the  preliminary  question.  Is  there  any  evidence  of 
physical  diffusion  or  filtration  in  the  kidney  ?  or,  to  put  it  another 
way,  is  there  any  evidence  of  a  urinary  flow  without  the  performance 
of  work  on  the  part  of  the  kidney  cells  ? 

The  answer  to  this  is  as  follows :  such  a  flow  cannot  take  place 
as  the  result  of  any  agency  which  alters  the  composition  of  the 
fluid ;  nevertheless,  the  appropriate  injection  into  the  circulation  of 


en.  xxxviu.]  LUDWIG'S  THEORY  577 

Ringer's  fluid  causes  a  copious  flow  of  urine  which  is  in  its  composi- 
tion virtually  Ringer's  fluid.  On  physico-chemical  grounds  such  a 
flow  would  not  necessarily  demand  work  on  the  part  of  the  kidney 
cells,  and  as  a  matter  of  fact,  estimation  of  the  oxygen  used  during 
such  excretion  reveals  no  measurable  rise  in  the  amount  of  work 
performed.  The  general  relationship  shown  in  the  table  on  p.  575, 
between  the  pressure  of  blood  in  the  kidney  capillaries  and  the 
volume  of  urine  secreted,  points  also  to  the  possibility  that  under 
normal  conditions  filtration  is  a  factor  in  urine  formation.  The  cells 
of  Bowman's  capsule,  thin  though  they  are,  can,  however,  exercise 
selective  action.  The  simplest  phase  of  this  is  that  massive 
molecules  (protein)  do  not  pass  through  them  in  health ;  this,  however, 
is  also  true  for  films  of  gelatin.  In  addition  to  this,  these  living 
cells  may  exercise  a  more  active  selection,  as  is  seen  in  the  type  of 
urine  excreted  by  kidneys  in  which  the  tubules  have  undergone 
necrosis  as  the  result  of  injection  of  uranium  salts. 

We  may  take  next  the  point  mentioned  last,  namely,  that  of 
reabsorption.  Carl  Ludwig  imagined  that  the  urine  filtered  off  at 
the  glomerulus  becomes  more  concentrated  as  it  descends  the 
tubule,  and  that  the  work  of  the  cells  in  the  tubule  is  to  reabsorb 
the  water  and  pass  it  back  into  the  blood.  There  is  in  our 
opinion  no  satisfactory  evidence  that  this  occurs ;  still  it  is  not 
possible  to  categorically  deny  its  existence ;  if  it  does  occur  it  does 
not  take  place  on  the  massive  scale  *  which  Lud wig's  views  involve, 
and  is  limited  to  the  clear  epithelium  of  the  descending  limb  of 
Henle's  loop.  The  majority  of  physiologists  do  not  admit  even  this, 
and  one  piece  of  evidence  which  we  owe  to  Brodie  appears  to  me 
to  be  quite  conclusive ;  it  is  this :  if  the  pressure  of  urine  in  the 
ureter  is  artificially  raised  by  partially  blocking  it,  absorption  of 
water  back  into  the  blood  ought  to  be  increased ;  but  as  a  matter 
of  fact  this  does  not  take  place,  but  the  exact  contrary,  for  the  flow 
of  urine  provoked  by  the  injection  of  sodium  sulphate  is  more 
abundant  from  the  kidney  with  the  partially  blocked  ureter,  than 
in  the  other  kidney  which  serves  as  a  control. 

This  brings  us  then  to  our  main  conclusion  concerning  the 
function  of  the  epithelium  of  the  tubular  part  of  the  apparatus. 
Here  undoubtedly  the  main  function  is  secretion,  and  the  obviously 
secreting  nature  of  the  cells  is  revealed  by  microscopic  examination. 
The  following  experiments,  among  others,  support  this  view : — 
(a)  In  frogs  the  glomeruli  can  be  cut  out  of  action  by  ligaturing  the 
renal  artery ;  the  kidney  is  then  supplied  only  by  the  renal  portal 
vein,  a  vessel  which  goes  to  the  tubules  only.  If  urea  is  then 
injected  under  the  skin,  a  secretion  of  urine  occurs,  which  though 

*  Ludwig's  theory  would  involve  the  reabsorption  of  nearly  70  litres  of  water 
in  the  day  ! 

2  O 


578  THE  URINARY  APPARATUS         [CH. 

scanty  in.  amount,  is  peculiarly  rich  in  urea.  Urea,  therefore,  in  the 
frog  is  secreted  by  the  epithelium  of  the  tubules.  In  order  to 
obtain  this  result,  the  kidney  must  receive  also  sufficient  oxygen  for 
the  maintenance  of  the  functional  activity  of  its  cells;  as  the 
arterial  supply  is  cut  off  by  ligature  of  the  renal  artery,  this  must 
be  accomplished  in  some  other  way,  for  instance,  by  keeping  the  frog 
during  the  experiment  in  an  atmosphere  of  pure  oxygen. 

(&)  The  same  result  is  reached  in  the  frog  in  another  way. 
The  renal  portal  system  of  the  frog's  kidney  may  be  artificially 
perfused  with  oxygenated  Kinger's  solution,  the  renal  arteries  as 
before  being  ligatured ;  if  certain  diuretics  are  added  to  the  solution 
(caffeine,  urea,  phloridzin,  sodium  sulphate,  etc.),  these  induce 
secretion  which  is  accompanied  by  a  marked  increase  in  the  oxygen 
consumption  of  the  kidney. 

(c)  In  mammals  the  arrangement  of  the  blood-vessels  is  different, 
and    it   is   not   possible   to   isolate   the    tubules    as    in   the   frog. 
Nevertheless,  the  same  diuretics  cause  a  copious  flow  of  urine,  which 
is  accompanied  in  all  cases  by  the  evidence  of  increased  work  on  the 
part  of   the  kidney  cells,  namely,  a  large  rise  in  the  amount  of 
oxygen  used  up.     In  all  these  cases  the  urine  secreted  is  unlike  the 
plasma  in   composition,   and    varies   somewhat   with    the   diuretic 
employed ;  for  instance,  injection  of  sodium  sulphate  produces  a  urine 
almost  devoid  of  chlorides. 

(d)  In  mammals  also  it  is  possible  to  trace  certain  substances 
with  the  eye.     A  research  of  great  importance  was  performed  along 
this  line  by  Heidenhain.     By  cutting  the  spinal  cord  he  removed 
the  arterial  tone  from  the  whole  visceral  area,  and  consequently 
produced  a  blood-pressure   so  low  that   no   fluid  came   down  the 
tubules.     Sulphindigotate  of  soda  is  a  nitrogenous  substance,  and 
it  can  easily  be  recognised  by  its  blue  colour.     If  it  is  injected  into 
the  blood-stream  it  is   excreted  by  the  liver  and  kidney,  and  on 
post-mortem  examination  of  the  kidney,  it  is  found  in  those  cells  of 
the  tubules  which  bear  the  impress  of  secreting  cells,  whereas  it  is 
absent  from  the  cells  of  Bowman's  capsule. 

Numerous  hypotheses  have  been  put  forward  to  explain  all 
these  results,  and  the  two  great  historic  theories  are  those  of 
Ludwig  and  of  Bowman.  The  gist  of  Lud wig's  views  will  have 
been  gathered  from  what  has  just  been  said ;  he  supposed  that 
the  urine  filtered  through  at  the  glomeruli  is  a  fluid  of  the 
same  general  composition  as  the  blood-plasma,  so  far  as  its 
crystalline  constituents  are  concerned,  and  that  this  fluid  is  gradu- 
ally turned  into  urine  as  it  travels  along  the  tubules  by  the 
absorption  from  it  into  the  blood  of  water  and  certain  salts. 
That  fluid  isotomic  with  blood-plasma  can  or  does  filter  through 
the  flat  epithelium  cells  of  Bowman's  capsule  appears  to  be  true,  but 


CH.  XXXYIII.]  EXTIKPATION   OF  THE  KIDNEYS  579 

the  part  of  the  theory  which  deals  with  reabsorption  we  have  seen 
reasons  for  not  accepting. 

The  general  appearance  of  the  capsular  epithelium  resembles 
that  lining  a  lymph  space,  and  some  morphologists  hold  the  view 
that  each  capsule  is  in  development  part  of  the  peritoneum,  whilst 
others  regard  it  as  part  of  the  kidney  tubule.  It  is  possible 
that  the  glomerulus  has  other  functions  besides  that  of  a  filter. 
Brodie,  for  instance,  has  suggested  that  its  main,  if  not  its 
only  use  is  that  of  a  driving  force  to  propel  the  secreted  urine 
along  the  tubule,  the  resistance  of  which  is  very  great;  he  has 
invented  models  which  demonstrate  that  pulsations  of  the  kind 
alleged  to  occur  in  the  glomeruli  will  drive  fluid  along  a  tube ; 
he  further  supports  his  theory  by  the  observation  that  the  maximum 
pressure  in  the  ureter  as  measured  by  a  manometer  is  usually  at 
least  30  to  44  mm.  of  mercury  less  than  the  arterial  blood-pressure, 
and  is  probably  equal  to  the  pressure  in  the  glomerular  capillaries. 
But  these  views  have  not  at  present  been  fully  accepted  by  the 
majority  of  physiologists. 

Bowman's  classical  theory  was  formulated  more  than  seventy 
years  ago,  that  is,  long  before  many  of  the  experiments  just  described 
were  performed.  It  accords  much  more  nearly  with  modern  views 
than  that  of  Ludwig,  and  was  founded  mainly  as  a  deduction  from 
anatomical  structure,  namely,  the  histological  appearances  of  the 
epithelial  cells  which  line  the  tubules,  and  the  double  vascular 
supply  which  in  the  frog  indicates  that  the  work  of  the  tubule  is 
distinct  from  that  of  the  glomerulus.  He  considered  that  the  cells 
lining  the  capsule  have  much  the  same  function  as  those  lining  a 
lymph  space,  and  that  it  is  the  glandular  epithelium  of  the  tubules 
which  secretes  the  nitrogenous  constituents  of  the  urine.  We  may 
accept  the  last  part  of  the  theory  as  now  definitely  proven.  But 
whether  the  glomerular  flow  is  conditioned  by  physical  or  by 
physiological  factors  is  the  main  point  at  issue  between  investigators 
at  present.  In  the  minds  of  both  Ludwig  and  Bowman  the  physical 
factor  was  uppermost.  Heidenhain,  and  more  recently  Brodie,  regard 
the  flat  glomerular  cells  as  true  secreting  cells.  Our  own  view  is 
that  although  active  secretion  on  the  part  of  these  cells  has  not 
been  proved  to  exist,  the  possibility  cannot  be  altogether  denied, 
and  as  will  be  gathered  from  what  has  preceded  this,  our  bias  is 
distinctly  in  favour  of  the  physical  or  filtration  hypothesis. 

Extirpation  of  the  Kidneys. 

Extirpation  of  one  kidney  for  stone,  etc.,  is  a  common  operation. 
It  is  not  followed  by  any  untoward  result.  The  remaining  kidney 
enlarges  and  does  the  work  previously  shared  between  the  two. 


580  THE   URINARY   APPARATUS  [CH.  XXXVIII. 

Extirpation  of  loth  kidneys  is  fatal ;  the  urea,  etc.,  accumulate  in 
the  blood,  and  the  animal  dies  in  a  few  days;  urseinic  convulsions 
do  not  usually  occur  in  such  experiments. 

Ligature  of  loth  renal  arteries  amounts  to  the  same  thing 
as  extirpation  of  the  kidneys,  and  leads  to  the  same  result.  If  the 
ligature  is  released  the  kidney  after  a  time  again  sets  to  work,  but  the 
urine  secreted  at  first  is  albuminous,  owing  to  the  epithelium  having 
been  impaired  by  being  deprived  for  a  time  of  its  blood  supply. 

The  Passage  of  Urine  into  the  Bladder. 

As  each  portion  of  urine  is  secreted  it  propels  that  which  is 
already  in  the  uriniferous  tubes  onwards  into  the  pelvis  of  the 
kidney.  Thence  through  the  ureter  the  urine  passes  into  the  bladder, 
into  which  its  rate  and  mode  of  entrance  has  been  watched  in  cases 
of  ectopia  vesicce,  i.e.  of  such  fissures  in  the  anterior  and  lower  part  of 
the  walls  of  the  abdomen,  and  of  the  front  wall  of  the  bladder,  as 
expose  to  view  its  hinder  wall  together  with  the  orifices  of  the  ureters. 
The  urine  does  not  enter  the  bladder  at  any  regular  rate,  nor  is  there 
a  synchronism  in  its  movement  through  the  two  ureters.  During  fast- 
ing, two  or  three  drops  enter  the*  bladder  every  minute ;  each  drop  a's 
it  enters  first  raises  up  the  little  papilla  through  which  the  ureter 
opens,  and  then  passes  slowly  through  its  orifice,  which  at  once  again 
closes  like  a  sphincter.  Its  flow  is  aided  by  the  peristaltic 
contractions  of  the  ureters,  and  is  increased  in  deep  inspira- 
tion, or  by  straining,  and  in  active  exercise,  and  in  fifteen 
or  twenty  minutes  after  a  meal.  The  urine  is  prevented  from 
regurgitation  into  the  ureters  by  the  mode  in  which  these  pass 
through  the  walls  of  the  bladder,  namely,  by  their  lying  for  between 
half  and  three-quarters  of  an  inch  between  the  muscular  and  mucous 
coats  before  they  turn  rather  abruptly  forwards,  and  open  through 
the  latter  into  the  interior  of  the  bladder. 

Micturition. 

The  desire  to  void  the  urine  arises  from  a  sense  of  fullness  of 
the  bladder,  and  the  increase  of  pressure  in  this  viscus,  which  results 
from  its  distension,  is  probably  the  most  important  factor  in  the 
causation  of  the  reflex.  Mosso  states  that  in  the  dog's  bladder  a 
pressure  of  20  cms.  of  water  sets  the  reflex  in  action. 

The  afferent  impulse  so  produced  finds  its  way  to  the  sacral 
region  of  the  cord  chiefly  through  the  second  and  third  sacral  nerves, 
and  stimulates  the  so-called  vesical  centre,  which  is  situated  in  the 
grey  matter  there ;  the  reflex  takes  place  perfectly  well  in  an  animal 
whose  spinal  cord  has  been  cut  across  as  low  as  the  lower  part  of  the 
lumbar  region.  It  has  therefore  been  proved  that  the  reflex  centre 


CH.  XXXVIII.]  MICTURITION  581 

must  be  situated  below  this  point.  In  such  animals  there  is  no 
consciousness  of  the  afferent  impulse,  and  the  same  is  true  for  the 
human  subject  with  corresponding  injuries  to  the  spinal  cord. 
Such  animals  or  men  have  also  no  voluntary  control  over  the  act;  it 
occurs  in  them  purely  reflexly. 

The  efferent  nerves  to  the  bladder  fall  into  two  sets :—  (1)  The 
nervus  erigens ;  this  is  undoubtedly  the  more  important  of  the  two. 
Stimulation  of  this  nerve  causes  contraction  of  the  bladder,  and 
relaxation  of  its  sphincter,  the  two  necessary  acts  by  which  the 
urine  is  expelled.  (2)  The  hypoyastric  nerves;  pre-ganglionic  fibres 
leave  the  cord  in  the  lumbar  region,  pass  thence  to  the  inferior 
mesenteric  ganglion,  from  the  cells  of  which  the  post-ganglionic  fibres 
ultimately  reach  the  bladder  by  the  hypogastric  nerves.  Much 
difference  of  opinion  has  been  expressed  regarding  the  action  of  these 
nerves,  but  in  most  animals  they  cause  constriction  of  the  sphincter, 
and  in  some  cases  relaxation  of  the  bladder  walls  also.  The  hypo- 
gastric  nerves  would  therefore  appear  to  be  the  functional  anta- 
gonists of  the  nervi  erigentes.  In  many  animals  the  bladder 
constantly  exhibits  rhythmic  contractions. 

In  theory,  therefore,  micturition  is  a  reflex  action ;  but  in  practice 
it  is  a  voluntary  act,  and  the  voluntary  muscles  of  the  abdomen  press 
upon  the  bladder  and  assist  its  emptying.  It  is  only  in  the  cases  of  cord 
injury  or  disease  already  alluded  to  that  the  voluntary  factor  is  absent. 

The  simplest  view  to  take  of  voluntary  micturition  is  the  follow- 
ing : — The  will  causes  the  abdominal  muscles  to  contract,  and  the 
increased  pressure  on  the  bladder  so  produced  is  the  signal  for  the 
reflex  to  occur.  It  is  further  probable  that  the  mere  thought  of 
micturition  may  influence  the  sacral  vesical  centre,  and  heighten  its 
sensitiveness.  This  certainly  is  the  case  in  the  neighbouring 
centre  for  the  erection  of  the  penis ;  erection  can '  be  evoked  as  a 
reflex  act,  yet  it  is  a  matter  of  experience  that  it  also  takes  place 
as  a  result  of  the  emotions. 

If  urine  is  voided  too  frequently,  the  cause  may  be  (1)  peripheral, 
as  in  inflammation  of  the  bladder  ;  here  the  organ  is  unduly  sensitive 
to  the  pressure  of  fluid;  and  (2)  central,  as  in  cases  of  fear  and 
excitement ;  here  the  sensibility  of  the  vesical  centre  is  heightened. 
In  children  where  control  of  the  vesical  centre  is  often  not  fully 
established  while  they  are  young,  frequent  and  involuntary  micturi- 
tion may  occur. 

Deficiency  of  power  to  expel  the  urine  may  be  due  to  actual 
obstruction,  from  an  enlarged  prostate  or  a  stricture  in  the  urethra. 
It  may  also  be  due  to  weakness  of  the  bladder,  as  in  cases  where 
the  organ  is  much  distended  and  its  musculature  attenuated;  this 
condition  is  often  secondary  to  obstruction  produced  by  stricture,  or 
other  causes. 


CHAPTER  XXXTX 

THE  URINE 

Quantity. — A  man  of  average  weight  and  height  passes  from  1400 
to  1600  e.c.,  or  about  50  fluid  oz.  daily.  This  contains  about  60 
grammes  (1J  oz.)  of  solids. 

Colour. — This  is  some  shade  of  yellow  which  varies  considerably 
with  the  concentration  of  the  urine.  It  is  due  to  a  mixture  of  pig- 
ments ;  of  these  the  most  abundant  is  a  yellow  one,  originally 
named  urochrome  by  Thudichum,  whose  investigations  have  in  the 
main  been  confirmed  and  supplemented  by  the  recent  work  of 
Dombrowski.  It  shows  no  absorption  bands,  and  does  not  fluoresce 
with  zinc  -salts  as  urobilin  does.  It  yields  a  pyrrol  derivative 
which  is  not  haemopyrrol,  and  so  urochrome  is  probably  not  related 
to  urobilin.  It  contains  11-1  per  cent,  of  nitrogen  and  5  per  cent, 
of  sulphur,  most  of  which  is  easily  split  off  as  sulphide  by  cold 
alkali.  It  is  probably  derived  from  protein. 

Urobilin,  which  is  normally  present  in  small  quantities  only, 
has  a  reddish  tint,  and  like  bile  pigment  is  an  iron-free  substance. 
It  has  an  absorption  band  near  the  F  line.  The  bile  pigment  in 
the  intestines  is  converted  into  stercobilin,  most  of  which  leaves  the 
body  with  the  faeces ;  some,  however,  is  reabsorbed  and  is  excreted 
into  the  urine,  and  is  then  called  urobilin  (see  p.  534).  A  chromogen 
or  mother-substance  called  urobilinogen,  which  by  oxidation — for 
instance,  standing  exposed  to  the  air — is  converted  into  the  pigment 
proper,  is  more  abundant  than  urobilin  itself.  In  certain  diseased 
conditions  the  amount  of  urobilin  is  considerably  increased. 

Uroerythrin,  the  colouring  matter  of  pink  urate  sediments, 
appear  to  be  a  small  but  constant  constituent  of  urine,  but  its 
origin  is  unknown.  Normal  urine  contains  also  a  trace  of  hcemato- 
porphyrin,  and  the  amount  is  increased  in  certain  diseased  states. 

Reaction. — The  reaction  of  normal  urine  is  acid ;  this  is  not  due 
to  free  acid,  but  to  acid  salts,  of  which  acid  sodium  phosphate  is  the 
most  important.  The  uric  and  hippuric  acids  of  the  urine  are 
combined  as  urates  and  hippurates  respectively.  Under  certain 
circumstances  the  urine  becomes  less  acid  and  even  alkaline;  the 
most  important  of  these  are  as  follows : — 

582 


CH.  XXXIX.] 


COMPOSITION    OF    URINE 


583 


1.  During  digestion.     Here  there  is  a  formation  of  free  acid  in 
the  stomach,  and  a  corresponding  liberation  of  bases  in  the  blood, 
which,  passing  into  the  urine,  diminish  its  acidity,  or  even  render  it 
alkaline.     This  is  called  the  alkaline  tide ;  the  opposite  condition,  the 
acid  tide,  occurs  after  a  fast — for  instance,  before  breakfast. 

2.  In  herbivorous  animals  and  vegetarians.     The  food  here  con- 
tains excess  of  alkaline  salts  of  acids  such  as  tartaric,  citric,  malic,  etc. 
These  acids  are  oxidised  into  carbonates,  which,  passing  into  the  urine, 
give  it  an  alkaline  reaction. 

Specific  Gravity. — The  specific  gravity  varies  inversely  as  the 
quantity  of  urine  passed  under  normal  conditions  from  1015  to 
1025.  A  specific  gravity  below  1010  should  excite  suspicion  of 
hydruria;  one  over  1030,  of  a  febrile  condition,  or  of  diabetes,  a 
disease  in  which  it  may  rise  to  1050.  The  specific  gravity  has, 
however,  been  known  to  sink  as  low  as  1002  (after  large  potations, 
urina  potus),  or  to  rise  as  high  as  1035  (after  great  sweating)  in 
perfectly  healthy  persons. 

Composition. — The  following  table  gives  the  average  amounts  of 
the  urinary  constituents  passed  by  a  man  taking  an  ordinary  diet 
containing  about  100  grammes  of  protein  in  the  twenty-four  hours : — 


Total  quantity  of  urine 

Water       . 

Solids       . 

Urea 

Uric  acid 

Hippuric  acid  . 

Sodium  chloride 

Phosphoric  acid 

Sulphuric  acid 

Ammonia 

Creatinine 

Chlorine  . 

Potassium 

Sodium    . 

Calcium   . 

Magnesium 


1500-00  grammes. 
1440-00 
60-00 
35-00 

0-75 

1-05 
16-5 

3-5 

2-0 

0-65 

0-9 
11-0 

2-5 

5-5 

0-26 

0-21 


The  most  abundant  constituents  of  the  urine  are  water,  urea,  and 
sodium  chloride.  In  the  foregoing  table  one  must  not  be  misled  by 
seeing  the  names  of  the  acids  and  metals  separated.  The  acids  and 
the  bases  are  combined  to  form  salts,  such  as  urates,  chlorides, 
sulphates,  phosphates,  etc. 

Urea. 

Urea,  or  Carbamide,  CO(NH2)2,  is  isomeric  (that  is,  has  the  same 
empirical,  but  not  the  same  structural  formula)  with  ammonium 
cyanate  (NHJCNO,  from  which  it  was  first  prepared  synthetically 
by  Wohler  in  1828.  Since  then  it  has  been  prepared  synthetically 
in  other  ways.  Wohler's  observation  derives  interest  from  the  fact 


584 


THE  URINE 


[CH.  XXXIX. 


that  this  was  the  first  organic  substance  which  was  prepared  syntheti- 
cally by  chemists.* 

When  crystallised  out  from  the  urine  it  is  found  to  be  readily 
soluble  both  in  water  and  alcohol :  it  has  a  saltish  taste,  and  is  neutral 

to    litmus    paper.      The   form    of    its 
crystals  is  shown  in  fig.  378. 

When  treated  with  nitric  acid, 
nitrate  of  urea  (CON2H4 .  HN03)  is 
formed ;  this  crystallises  in  octahedra, 
lozenge-shaped  tablets  or  hexagons  (fig. 
379).  When  treated  with  oxalic  acid, 
flat  or  prismatic  crystals  of  urea  oxa- 
late(CON2H4.H20204  +  H20)  are  formed 
(fig.  880). 


These  crystals  may  be  readily  ob- 
lined  by  adding  excess  of 


FIG.  378.— Crystals  of  urea. 


tained  by  adding  excess  of  the  respective 
acids  to  urine  which  has  been  concen- 
trated to  a  third  or  a  quarter  of  its  bulk. 
Under    the    influence    of    a    micro-organism,    the    niicrococcus 
urese,  which   grows   readily   in   stale   urine,  urea   takes   up  water, 
and   is    converted   into    ammonium    carbonate    [CON2H4  +  2H20  = 
(NH4)2C03].     Hence  the  ammoniacal  odour  of  putrid  urine. 

By  means  of  nitrous  acid,  urea  is  broken  up  into  carbonic  acid, 
water,   and   nitrogen,   CONH  +  2HN0  =  C0  +  3H0  +  2N.       The 


FIG.  379.— Crystals  of  urea  nitrate. 


FIG.  380. — Crystals  of  urea  oxalate. 


evolution  of  gas  bubbles  which  takes  place  on  the  addition  of  fuming 
nitric  acid  may  be  used  as  a  test  for  urea. 

Hypobromite  of  soda  decomposes  urea  in  the  following  way  :  — 


CON2H4   +    SNaBrO   =    CO 


N 


[Urea.] 


2H9O 


[Sodium  [Carbonic  [Nitrogen.]     [Water.] 

hypobromite.]         acid.] 


SNaBr. 

[Sodium 
bromide.] 


This  reaction  is  important,  for  on  it  one  of  the  readiest  methods 
for  estimating  urea  depends.  There  have  been  various  pieces  of 

*  Meldola  has  pointed  out  that  the  English  chemist  Henry  Hennell  prepared 
alcohol  from  olefiant  gas  simultaneously  with  Wohler's  synthesis  of  urea.  The 
honour  of  founding  the  science  of  organic  chemistry  must,  therefore,  be  shared 
between  the  two  men. 


CH.  XXXIX.] 


ESTIMATION   OF  UREA 


585 


apparatus  invented  for  rendering  the  analysis  easy;  but  the  one 
described  below  is  the  best.  If  the  experiment  is  performed  as 
directed,  nitrogen  is  the  only  gas  that  comes  off,  the  carbonic  acid 
being  absorbed  by  excess  of  soda.  The  amount 
of  nitrogen  is  a  measure  of  the  amount  of  urea. 

Dupre's  apparatus  (fig.  381)  consists  of  a  bottle  (A) 
united  to  a  measuring  tube  by  india-rubber  tubing.  The 
measuring  tube  (C)  is  placed  within  a  cylinder  of  water 
(D),  and  can  be  raised  and  lowered  at  will.  Measure 
25  c.c.  of  alkaline  solution  of  sodium  hypobromite 
(made  by  mixing  2  c.c.  of  bromine  with  23  c.c.  of  a  40 
per  cent  solution  of  caustic  soda)  into  the  bottle  A. 
Measure  5  c.c.  of  urine  into  a  small  tube  (B),  and  lower 
it  carefully,  so  that  no  urine  spills,  into  the  bottle. 
Close  the  bottle  securely  with  a  stopper  perforated  by 
a  glass  tube ;  this  glass  tube  (the  bulb  blown  on  this 
tube  prevents  froth  from  passing  into  the  rest  of  the 
apparatus)  is  connected  to  the  measuring  tube  by  india- 
rubber  tubing  and  a  "["-piece.  The  third  limb  ®f  the 
T -piece  is  closed  by  a  piece  of  india-rubber  tubing  and 
a  pinch-cock,  seen  at  the  top  of  the  figure.  Open  the 
pinch-cock  and  lower  the  measuring  tube  until  the  sur- 
face of  the  water  with  which  the  outer  cylinder  is  filled 
is  at  the  zero  point  of  the  graduation.  Close  the  pinch- 
cock,  and  raise  the  measuring  tube  to  ascertain  if  the 
apparatus  is  air-tight.  Then  lower  it  again.  Tilt  the 
bottle  A  so  as  to  upset  the  urine,  and  shake  well  for  a 
minute  or  so.  During  this  time  there  is  an  evolution 
of  gas.  Then  immerse  the  bottle  in  a  large  beaker  con- 
taining water  of  the  same  temperature  as  that  in  the 
cylinder.  After  two  or  three  minutes  raise  the  measur- 
ing tube  until  the  surfaces  of  the  water  inside  and  out- 
side it  are  at  the  same  level  Read  off  the  amount  of 
gas  (nitrogen)  evolved.  35 '4  c.c.  of  nitrogen  are  yielded 
by  0*1  gramme  of  urea.  From  this  the  quantity  of  urea 
in  the  5  c.c.  of  urine  and  the  percentage  of  urea  can  be 
calculated.  If  the  total  urea  passed  in  the  twenty-four 
hours  is  to  be  ascertained,  the  twenty-four  hours'  urine 
must  be  carefully  measured  and  thoroughly  mixed. 
A  sample  is  taken  from  the  total  for  analysis ;  and 
then,  by  a  simple  sum  in  proportion,  the  total  amount 
of  urea  is  ascertained. 

Folin's  method  is  the  best  for  accurate  work;  it  depends  on  the  fact  that 
urea  is  decomposed  into  ammonia  and  carbonic  acid  by  boiling  with  magnesium 
chloride  in  the  presence  of  hydrochloric  acid.  The  ammonia  is  estimated  by 
distilling  it  into  standard  acid  and  subsequent  titration. 

Kjelda.hl's  method  of  estimating  nitrogen  consists  in  boiling  the  material  under 
investigation  with  strong  sulphuric  acid.  The  nitrogen  present  is  by  this  means 
converted  into  ammonia.  Excess  of  soda  is  then  added,  and  the  ammonia  distilled 
over  into  a  known  volume  of  standard  acid.  The  amount  of  diminution  of  aridity 
in  the  standard  enables  one  to  calculate  the  amount  of  ammonia,  and  thence  the 
amount  of  nitrogen.  This  is  the  best  method  for  the  estimation  of  the  total 
nitrogen  in  the  urine. 

The  quantity  of  urea  is  variable,  the  chief  cause  of  variation 
being  the  amount  of  protein  food  ingested.  In  a  man  in  a  state  of 


FIG.  381.— Dupre's  Urea 
Apparatus. 


586  THE   URINE  [CH.  XXXIX. 

nitrogenous  equilibrium,  taking  daily  100  to  120  grammes  of  protein  in 
his  food,  the  quantity  of  urea  secreted  daily  is  about  33  to  35  grammes 
(500  grains).  The  percentage  in  human  urine  would  then  be  2  per 
cent.;  but  this  also  varies,  because  the  concentration  of  the  urine 
varies  considerably  in  health.  In  dogs  it  may  be  10  per  cent. 
The  excretion  of  urea  is  usually  at  a  maximum  three  hours  after  a 
meal,  especially  after  a  meal  rich  in  proteins.  If,  therefore,  people 
adopt  the  Chittenden  diet,  which  contains  about  half  the  quantity  of 
protein  which  is  present  in  the  more  usual  Voit  dietary,  their  urine 
will  naturally  show  a  nitrogenous  output  of  half  of  that  which  is  now 
regarded  as  normal.  In  those  who  adopt  such  a  reduced  diet,  Folin 
has  shown  that  the  decrease  in  urinary  nitrogen  falls  mainly  on  the 
urea  fraction,  and  in  some  cases  the  urea  excreted  accounted  for  only 
66  per  cent,  of  the  total  nitrogen.  The  other  nitrogenous  katabolites 
of  the  urine  alter  comparatively  little  under  such  circumstances,  and 
the  creatinine  in  particular  remains  remarkably  constant  in  amount. 

In  our  study  of  protein  absorption  (p.  545),  we  have  already 
indicated  that  the  amino-acid  fragments  of  the  food-protein  are 
utilised  in  two  ways.  A  small  part  is  used  by  the  tissue  cells  for 
the  reconstruction  of  their  protein  which  has  undergone  katabolism. 
In  time  this  will  in  turn  be  katabolised,  and  the  waste  products 
discharged  as  ammonia,  creatinine,  and  a  certain  amount  of  urea. 
This  form  of  metabolism  may  be  termed  tissue  or  endogenous 
metabolism,  and  its  amount  is  constant  and  independent  to  a  great 
extent  of  the  food.  The  other  and  larger  part  of  the  cleavage  pro- 
ducts of  the  food  protein  are  not  made  use  of  thus,  but  are 
deamidised,  and  the  nitrogenous  portion  is  converted  into  urea  by 
the  liver,  and  discharged  by  the  kidney.  This  part  of  metabolism 
may  be  termed  exogenous ;  it  is  variable  in  amount,  and  depends  on 
the  quantity  of  ingested  protein. 

That  the  liver  is  the  organ  where  urea  is  made  is  shown  by  the 
following  considerations : — 

1.  After  removal  of  the  liver   in   such   animals   as   frogs,  urea 
formation  almost  ceases,  and  ammonia  is  found  in  the  urine  instead. 

2.  In  mammals,  the  extirpation  of  the  liver  is   such   a   severe 
operation  that  the  animals  do  not  live.     But  the  liver  of  mammals 
can  be  very  largely  thrown  out  of  gear  by  connecting  the  portal  vein 
directly  to  the  inferior  vena  cava  (Eck's  fistula).     This  experiment 
has  been  done  successfully  in  dogs ;  the  amount  of  urea  in  the  urine 
is  lessened,  and  its  place  is  taken  by  ammonia. 

3.  When  degenerative  changes  occur  in  the  liver,  as  in  cirrhosis 
of  that  organ,  the  urea  formed  is  much  lessened,  and  its  place  is 
taken  by  ammonia.     In  acute  yellow  atrophy  urea  is  almost  absent  in 
the  urine,  and,  again,  there  is  considerable  increase  in  the  ammonia. 
In  this  disease  ammo-acids  such  as  leucine  and  tyrosine  are  also  found 


CH.  XXXIX.]  OKIGIN   OF   UREA  587 

in  the  urine ;  they  arise  from  the  disintegration  of  the  proteins  of 
the  liver  cells,  but  they  may  in  part  originate  in  the  intestine,  and, 
escaping  further  decomposition  in  the  degenerated  liver,  pass  as  such 
into  the  urine. 

That  the  ammo-acids  are  the  substances  from  which  the  liver 
forms  urea  is  shown  by  the  fact  that  if  such  amino-acids  as  glycine, 
leucine,  arginine,  etc.,  are  administered  by  the  mouth,  or  injected 
into  the  blood-stream,  the  excretion  of  urea  is  correspondingly 
raised. 

The  transformation  of  arginine  into  urea  is  a  subject  on  which  we 
have  more  accurate  information  than  in  the  case  of  any  other  amino- 
acids,  for  there  is  no  doubt  that  the  change,  which  can  be  brought 
about  in  a  test-tube,  is  also  accomplished  in  the  organism.  If  the 
account  of  arginine  given  on  p.  420  is  referred  to,  it  will  be  seen  to 
consist  of  a  urea  radical  and  a  substance  called  ornithine.  On 
hydrolysis  we  therefore  get  urea  and  ornithine  (diamino-valeric 
acid),  and  this  in  the  body  is  accomplished  by  a  special  enzyme 
called  arginase  (Kossel  and  Dakin),  which  is  more  abundant  in  the 
liver  than  in  any  other  tissue.  The  actual  yield  of  urea  is,  however, 
greater  than  one  would  anticipate,  and  so  it  must  be  supposed  that 
the  ornithine  in  its  turn  is  broken  up  and  urea  is  the  result.  If  we 
glance  at  the  formula  of  ornithine,  and  compare  it  with  that  of  certain 
other  amino-acids  which  are  also  undoubted  urea  forerunners,  we 
have  the  following : — 

Glycine C2H5NO, 

Leucine C6H13NO.2 

Ornithine C5H12N2O2 

In  all  cases,  the  atoms  of  carbon  are  more  numerous  than  those  of 
nitrogen.  In  urea  (CON2H4)  the  reverse  is  the  case.  The  amino- 
acids  must  therefore  be  split  into  simpler  compounds  which  unite 
with  one  another  to  form  urea.  Urea  formation  is  thus,  in  part, 
synthetic.  These  simpler  compounds  are  ammonium  salts.  Schroder's 
work,  which  has  been  confirmed  by  subsequent  investigators,  proves 
that  ammonium  carbonate  is  one  of  the  urea  precursors,  if  not  the 
principal  one.  The  equation  which  represents  the  reaction  is  as 
follows : — 

(NH4)2CO3   =    CON2H4    +    2H2O. 

[Ammonium  [Urea."] 

carbonate.] 

Schroder's  principal  experiment  was  this:  a  mixture  of  blood  and 
ammonium  carbonate  was  injected  into  the  liver  by  the  portal  vein ; 
the  blood  leaving  the  liver  by  the  hepatic  vein  was  found  to  contain 
urea  in  abundance.  This  does  not  occur  when  the  same  experi- 
ment is  performed  with  any  other  organ  of  the  body,  so  that 
Schroder's  experiments  also  prove  the  great  importance  of  the  liver 


588  THE  URINE  [CH.  XXXIX. 

in  urea  formation.     Similar  results  were  obtained  by  Nencki  with 
ammonium  carbamate. 

The  importance  of  ammonia  is  accentuated  when  we  remember 
that  ammonia  is  one  of  the  products  of  pancreatic  digestion,  and 
probably  also  of  endogenous  protein  metabolism.  The  ammonia, 
whether  it  is  formed  directly  or  through  the  intermediate  stage  of 
amino-acid,  will  combine  with  the  carbonic  acid  of  the  blood  to  form 
ammonium  carbonate  or  carbamate,  and  the  following  structural 
formulae  exhibit  the  close  relationship  between  these  substances  and 
urea.  The  loss  of  one  molecule  of  water  from  ammonium  carbonate 
produces  ammonium  carbamate;  the  loss  of  a  second  molecule  of 
water  produces  urea  — 


/O.NH4  r/NH2 

O  -  C\O.NH*  '\O.NH4 

[Ammonium  carbonate.]  [Ammonium  carbamate.]  [Urea  or  carbamide.] 

Urea  is  absent,  or  nearly  so,  from  the  muscles,  and  its  place  there 
is  taken  by  the  substance  called  creatine.  It  is,  however,  doubtful 
whether  creatine  is  a  precursor  of  urea  in  the  body.  The  fact  that 
muscular  work  does  not  appreciably  increase  protein  katabolism  is 
intelligible,  when,  in  light  of  recently  acquired  knowledge,  we  realise 
that  protein  katabolism,  in  so  far  as  its  nitrogen  is  concerned,  is 
independent  of  the  oxidations  which  give  rise  to  heat,  or  to  the 
energy  which  is  converted  into  work. 

Urcemia.  —  The  older  authors  considered  that  urea  was  formed  in  the  kidneys, 
just  as  they  also  erroneously  thought  that  carbonic  acid  was  formed  in  the  lungs. 
Prevost  and  Dumas  were  the  first  to  show  that  after  complete  extirpation  of  the 
kidneys  the  formation  of-  urea  goes  on,  and  that  it  accumulates  in  the  blood  and 
tissues.  Similarly,  in  those  cases  of  disease  in  which  the  kidneys  cease  work,  urea 
is  still  formed  and  accumulates.  This  condition  is  called  uraemia,  and  unless  the 
products  of  nitrogenous  breakdown  are  discharged  from  the  body  the  patient  dies 
in  a  condition  of  coma  preceded  by  convulsions. 

This  term  was  originally  applied  on  the  erroneous  supposition  that  it  is  urea  or 
some  antecedent  of  urea  which  acts  as  the  poison.  There  is  no  doubt  that  the 
poison  is  not  any  constituent  of  normal  urine  ;  if  the  kidneys  of  an  animal  are 
extirpated,  the  animal  dies  in  a  few  days,  but  there  are  no  uraemic  convulsions. 
In  man,  also,  if  the  kidneys  are  healthy,  or  approximately  so,  and  suppression  of 
urine  occurs  from  the  simultaneous  blocking  of  both  renal  arteries  by  clot,  or  of  both 
ureters  by  stones,  again  uraemia  does  not  follow.  On  the  other  hand,  uraemia  may 
occur  even  while  a  patient  with  diseased  kidneys  is  passing  a  considerable  amount 
of  urine.  What  the  poison  is  that  is  responsible  for  the  convulsions  and  coma,  is 
unknown.  It  is  doubtless  some  abnormal  katabolic  product,  but  whether  this  is 
produced  by  the  diseased  kidney  cells,  or  in  some  other  part  of  the  body,  is  also 
unknown. 

Ammonia. 

A  small  quantity  of  ammonia  always  slips  through  into  the  urine, 
because  a  portion  of  the  ammonia-containing  blood  passes  through  the 
kidney  before  reaching  the  organs  that  are  capable  of  converting  it  into 
urea.  In  man  the  daily  amount  of  ammonia  excreted  varies  between 


CH.  XXXIX.]  AMMONIA  589 

0'3  and  1/2  grammes;  the  average  is  0*7  gramme.  The  ingestion  of 
ammonium  carbonate  does  not  increase  the  amount  of  ammonia  in 
the  urine,  but  increases  the  amount  of  urea,  into  which  substance  the 
ammonium  carbonate  is  easily  converted.  But  if  a  more  stable  salt, 
such  as  ammonium  chloride,  is  given,  it  appears  as  such  in  the  urine. 

Under  normal  conditions  the  amount  of  ammonia  depends  on 
the  adjustment  between  the  production  of  acid  substances  in  met- 
abolism and  the  supply  of  bases  in  the  food.  Ammonia  formation  is 
the  physiological  remedy  for  deficiency  of  bases. 

When  the  production  of  acids  is  excessive  (as  in  diabetes),  or 
when  mineral  acids  are  given  by  the  mouth  or  injected  into  the 
blood-stream,  the  result  is  an  increase  of  the  physiological  remedy, 
and  excess  of  ammonia  passes  over  into  the  urine.  Under  normal 
circumstances  ammonia  is  kept  at  a  minimum,  being  finally  converted 
into  the  less  toxic  substance  urea,  which  the  kidneys  easily  excrete. 
The  defence  of  the  organism  against  acids  which  are  very  toxic,  is  an 
increase  of  ammonia  formation,  or,  to  put  it  more  correctly,  less  of 
the  ammonia  formed  is  converted  into  urea. 

Under  the  opposite  conditions,  namely,  excess  of  alkali,  either  in 
food  or  given  as  such,  the  ammonia  disappears  from  the  urine,  all 
being  converted  into  urea.  Hence  the  diminution  of  ammonia  in  the 
urine  of  man  on  a  vegetable  diet,  and  its  absence  in  the  urine  of 
herbivorous  animals. 

Not  only  is  this  the  case,  but  if  ammonium  chloride  is  given  to  a 
herbivorous  animal  such  as  a  rabbit,  the  urinary  ammonia  is  but  little 
increased.  It  reacts  with  sodium  carbonate  in  the  tissues,  forming 
ammonium  carbonate  (which  is  excreted  as  urea)  and  sodium  chloride. 
Herbivora  also  suffer  much  more  from,  and  are  more  easily  killed  by, 
acids  than  carnivora,  their  organisation  not  permitting  a  ready  supply 
of  ammonia  to  neutralise  excess  of  acids. 

Creatine  and  Creatinine. 

Creatine  is  an  abundant   constituent  of   muscle;    its   chemical 
structure  is  very  like  that  of  arginine;  it  contains  a  urea  radical, 
and   by  boiling  it  with   baryta  it  splits  into  urea   and   sarcosine 
(methyl-glycine),  as  shown  in  the  following  equation : — 
C4H9N302   +   H,0   =   CON2H4   +   C3H7NO2. 

[Creatine.]  [Water.]  [Urea.]  [Sarcosine.] 

The  same  decomposition  is  shown  graphically  on  p.  420. 

Creatine  is  absent  from  normal  urine,  but  it  is  present  in  the 
urine  during  starvation,  in  acute  fevers,  in  women  during  involution 
of  the  uterus,  and  in  certain  other  conditions  in  which  there  is  rapid 
loss  of  muscular  material. 

Its  normal  fate  in  the  body  is  unknown ;  it  may  be  converted 
into  urea  as  in  the  foregoing  equation,  but  injection  of  creatine  into 


590  THE  URINE  [CH.  XXXIX. 

the  blood-stream  does  not  cause  any  increase  in  urea  formation ;  the 
creatine  injected  is  almost  wholly  excreted  unchanged. 

It  also  is  not  converted  into  creatinine,  although  it  has  been 
generally  assumed  that  this  conversion  does  occur.  The  transforma- 
tion of  creatine  into  creatinine  is  shown  in  the  following  equation  :— 

C4H9N3O2    -    H2O   =    C4H7N3O. 

[Creatine.]  [Water.]  [Creatinine.] 

Kecent  researches  have  entirely  failed  to  substantiate  the  view 
that  the  urinary  creatinine  originates  from  the  muscular  creatine. 
If  creatine  (an  innocuous  neutral  substance)  were  converted  by  the 
loss  of  water  in  the  muscles  into  creatinine  (a  strongly  basic 
substance),  it  would  be  contrary  to  all  that  is  known  of  the  chemical 
changes  that  occur  in  the  body. 

Creatinine  is  present  in  the  urine;  it  is,  in  fact,  next  to  urea  the 
most  abundant  nitrogenous  substance  found  there.  Amid  all  the 
inconstancies  of  urinary  composition,  it  appears  to  be  the  substance 
most  constant  in  amount,  diet  and  exercise  having  no  effect  on  it. 
Folin's  view,  that  its  amount  is  a  criterion  of  the  extent  of 
endogenous  nitrogenous  metabolism,  has  steadily  gained  ground,  and 
the  work  of  the  past  few  years  has  shown  that  the  liver  and  not  the 
muscles  is  the  seat  of  its  formation.  Some  observers  have  supposed 
that  certain  tissue  enzymes,  termed  creatase  and  creatinase,  are  agents 
in  its  formation  and  destruction ;  others  have  failed  to  discover  the 
presence  of  these  enzymes  in  the  liver.  On  this  and  on  other  points 
there  are  differences  of  opinion,  but  without  discussing  the  pros  and 
cons  of  minor  details,  the  following  view  of  Mellanby  may  be  taken 
as  a  working  hypothesis  of  the  metabolic  history  of  the  substances 
in  question.  Mellanby  took  as  his  starting-point  an  investigation  of 
the  contradictory  data  relating  to  the  proportion  of  creatine  and 
creatinine  in  muscle,  and  by  improved  methods  showed  that 
creatinine  is  never  present  in  muscle  at  all,  even  after  prolonged 
muscular  work.  He  then  studied  in  the  developing  bird  the  amount 
of  creatine  at  different  stages,  and  found  that  it  is  entirely  absent  in 
the  chick's  musculature  up  to  the  twelfth  day  of  incubation ;  after 
this  date  the  liver  and  the  muscular  creatine  develop  pari  passu. 
After  hatching,  the  liver  still  continues  to  grow  rapidly,  and  the 
creatine  percentage  in  the  muscles  increases  also,  although  the 
development  in  the  size  of  the  muscles  occurs  very  slowly.  This 
and  other  experiments  on  the  injection  of  creatine  and  creatinine 
into  the  blood-stream  finally  led  Mellanby  to  the  following  hypo- 
thesis : — Certain  products  of  protein  katabolism,  the  nature  of  which 
is  uncertain,  are  carried  by  the  blood  to  the  liver,  and  from  these  the 
liver  forms  creatinine ;  this  is  transported  to  the  muscles  and  there 
stored  as  creatine;  when  the  muscles  are  saturated  with  creatine, 


CII.  XXXIX.]  URIC   ACID  591 

excess  of  creatinine  is  then  excreted  by  the  kidneys.  The  small 
amount  of  creatinine  excreted  in  diseases  of  the  liver  also  supports 
the  view  that  that  organ  is  responsible  for  creatinine  formation. 

These  views  will  no  doubt  be  subjected  to  the  usual  tests  of 
criticism  and  renewed  research;  they  certainly  appear  to  explain 
some  of  our  previous  difficulties,  though  the  ultimate  fate  of  the 
muscular  creatine  is  still  unsolved. 

Uric  Acid. 

Uric  Acid  (C5N4H403)  is,  in  mammals,  the  medium  by  which  a 
very  small  quantity  of  nitrogen  is  excreted  from  the  body.  It  is, 
however,  in  birds  and  some  reptiles  the  principal  nitrogenous  con- 
stituent of  their  urine.  It  is  not  present  in  the  free  state,  but  is 
combined  with  bases  to  form  urates. 

It  may  be  obtained  from  human  urine  by  adding  5  c.c.  of  hydro- 
chloric acid  to  100  c.c.  of  the  urine,  and  allowing  the  mixture  to 
stand  for  twelve  to  twenty-four  hours.  The  crystals  which  form  are 
deeply  tinged  with  urinary  pigment,  and  though  by  repeated  solution 
in  caustic  soda  or  potash,  and  precipitation  by  hydrochloric  acid, 
they  may  be  obtained  fairly  free  from  pigment,  pure  uric  acid  is  more 
readily  obtained  from  the  solid  urine  of  a  serpent  or  bird,  which  con- 
sists principally  of  the  acid  ammonium 
urate.  This  is  dissolved  in  soda,  and 
then  the  addition  of  hydrochloric  acid 
produces  as  before  the  crystallisation  of 
uric  acid  from  the  solution. 

The  pure  acid  crystallises  in  colour- 
less rectangular  plates  or  prisms.  In 
striking  contrast  to  urea  it  is  a  most  in- 
soluble substance,  requiring  for  its  solu- 
tion 1900  parts  of  hot  and  15,000  parts 
of  cold  water.  The  forms  which  uric 
acid  assumes  when  precipitated  from 
human  urine,  either  by  the  addition  of 

,,         ,  ,       .  .  ,  f  .     .  .,  PIG.  382.— Various  forms  of  unc  acid 

hydrochloric  acid  or  in  certain  patho-  crystals, 

logical  processes,  are  very  various,  the 

most  frequent  being  the  whetstone  shape ;  there  are  also  bundles  of 
crystals  resembling  sheaves,  barrels,  and  dumb-bells  (see  fig.  382). 

The  murexide  test  is  the  principal  test  for  uric  acid.  The  test 
has  received  the  name  on  account  of  the  resemblance  of  the  colour 
to  the  purple  of  the  ancients,  which  was  obtained  from  certain  snails 
of  the  genus  Murex.  It  is  performed  as  follows :  place  a  little  uric 
acid  or  a  urate  in  a  capsule ;  add  a  little  dilute  nitric  acid  and 
evaporate  to  dryness.  A  yellowish-red  residue  is  left.  Add  a  little 
ammonia  carefully,  and  the  residue  turns  violet;  this  is  due  to  the 


592  THE   URINE  [CH.  XXXIX. 

formation  of  purpurate  of  ammonia.  On  the  addition  of  potash  the 
colour  becomes  bluer. 

Another  reaction  that  uric  acid  undergoes  (though  it  is  not 
applicable  as  a  test)  is,  that  on  treatment  with  certain  oxidising 
reagents  urea  and  oxalic  acid  can  be  obtained  from  it.  Alloxan 
(C4H2N204)  or  allantoin  (C^^Og)  are  intermediate  products.  It 
is,  however,  doubtful  whether  a  similar  oxidation  occurs  in  the 
normal  metabolic  processes  of  the  body. 

Uric  acid  is  dibasic,  and  thus  there  are  two  classes  of  urates — 
the  normal  urates  and  the  acid  urates.  A  normal  urate  is  one  in 
which  two  atoms  of  the  hydrogen  are  replaced  by  two  of  a  monad 
metal  such  as  sodium ;  an  acid  urate  is  one  in  which  only  one  atom  of 
hydrogen  is  thus  replaced.  The  formulae  would  be — 

C5H4N403  =   uric  acid. 
C5H3NaISr403  =   acid  sodium  urate. 
C5H2Na2N403  =   normal  sodium  urate. 

The  acid  sodium  urate  is  the  chief  constituent  of  the  pinkish  deposit 
of  urates,  which  often  occurs  in  urine,  and  is  called  the  lateritious 
deposit. 

If  uric  acid  is  represented  by  H.,U,  the  normal  urates  may  be  represented  by 
M2U,  and  the  acid  urates  by  MHU.  Bence  Jones,  and  later  Sir  W.  Roberts, 
considered  that  the  urates  actually  occurring  in  urine  are  what  are  termed  quadri- 
urates  MHU.H2U.  There  is  no  doubt  that  such  compounds  do  not  really  exist; 
they  are  merely  mixtures  of  acid  urate,  MHU,  and  free  uric  acid,  H2U. 

The  quantity  of  uric  acid  excreted  by  an  adult  varies  from  7  to 
10  grains  (0'5  to  0'7o  gramme)  daily. 

The  best  method  for  estimating  uric  acid  in  urine  is  that  of 
Hopkins  (Folin's  modification).  The  urine  is  made  alkaline  with 
ammonia  and  saturated  with  ammonium  sulphate.  This  precipitates 
all  the  uric  acid  as  ammonium  urate;  the  precipitate  is  collected  on 
a  filter,  and  washed  free  from  chlorides  with  a  10  per  cent,  solution 
of  ammonium  sulphate ;  it  is  then  rinsed  into  a  flask  with  hot  water ; 
when  cold,  sulphuric  acid  is  added.  It  is  then  titrated  at  60°  C. 
with  a  standard  solution  of  potassium  permanganate  until  a  perma- 
nent rose  colour  is  obtained.  From  the  amount  of  the  permanganate 
solution  used  to  obtain  the  end  point,  the  quantity  of  uric  acid 
present  is  calculated.  Uric  acid  may  also  be  determined  colori- 
metrically  by  the  blue  colour  it  strikes  with  phospho-tungstic  acid 
(Folin  and  A.  B.  Macallum,  jua). 

Origin  of  Uric  Acid. — Uric  acid  is  not  made  by  the  kidneys; 
when  these  organs  are  removed,  uric  acid  continues  to  be  formed, 
and  accumulates  in  the  organs,  especially  in  the  liver  and  the  spleen. 
After  extirpation  of  the  liver  in  birds  (in  which  animals  uric  acid  is 
such  an  important  katabolite),  the  formation  of  uric  acid  practically 
ceases,  and  its  place  is  taken  by  ammonia  and  lactic  acid,  and  the 


CH.  XXXIX.]  URIC   ACID  593 

conclusion  is  therefore  drawn  that  in  these  animals,  ammonia  and 
lactic  acid  are  normally  synthesised  in  the  liver  to  form  uric  acid. 

But  in  mammals,  this  is  not  the  history  of  uric  acid  formation ; 
in  these  animals,  including  man,  uric  acid  is  the  end-product  of  the 
metabolism  of  nuclein,  from  the  bases  of  which  it  arises  by  oxidation. 

Nuclein,  the  main  constituent  of  the  nuclei  of  cells  (see  p.  431), 
yields,  on  decomposition,  certain  products  called  purine  substances, 
and  their  close  relationship  to  uric  acid  is  shown  by  their  formulae : — 


Purine 

Hypoxanthine  (inonoxypurine) 


Purine  bases,'  Xanthine  (dioxypurine) 
^  Adenme  (ammo-purme) 


I 


Guanine  (amino-oxypurine) 
Uric  acid  (trioxypurine) 


C5H4N4 

C5H4N40 

C5H4N40., 

C5H3N4.NHo 

C5H3N4O.NH2 

C5H4N403 


Just  as  the  ordinary  protein  metabolism  is  both  exogenous  and 
endogenous,  so  is  it  the  case  with  nuclein  metabolism.  There  are 
certain  kinds  of  food  (such  as  liver  and  sweetbread)  which  are  rich 
in  nuclei,  and  others,  such  as  meat,  which  are  rich  in  purine  bases 
(especially  hypoxanthine).  The  increase  in  uric  acid  excretion  after 
partaking  of  such  food  is  exogenous,  and  those  liable  to  uric  acid 
disorders  should  avoid  such  articles  of  diet.  Other  forms  of  diet 
lead  to  an  increase  in  uric  acid  formation  by  increasing  the  number 
of  leucocytes  in  the  blood,  and  there  is  a  consequent  increase  in  the 
metabolism  of  their  nuclei.  Increase  in  leucocytes  may,  however,  be 
present  independently  of  diet,  and  in  the  disease  known  as  leucocy- 
thcemia,  this  occurs  to  a  marked  degree;  in  such  cases ^uric  acid 
formation  increases.  Although  special  attention  has  been  directed 
to  the  nuclei  of  leucocytes  because  these  can  readily  be  examined 
during  life,  it  must  be  remembered  that  the  nuclein  metabolism  of 
all  cells  may  contribute  to  uric  acid  formation.  Uric  acid,  which 
originates  by  metabolism,  is  spoken  of  as  endogenous. 

We  must  next  consider  the  mechanism  by  which  the  tissue  cells 
form  uric  acid  from  nuclein.  ,This  question  is  not  only  of  interest 
in  itself,  but  also  because  it  illustrates  a  general  truth  concerning 
the  importance  of  the  tissue  enzymes.  The  enzyme  of  the  liver 
which  turns  glycogen  into  sugar  is  the  oldest  known  example  of 
these;  in  more  recent  times,  the  importance  of  autolytic  enzymes 
(see  pp.  136  and  440)  of  tissue  erepsins  (see  p.  546)  and  arginase 
(see  p.  587)  has  been  recognised.  In  uric  acid  formation  we  have 
the  very  striking  example  of  the  action  of  a  succession  of  enzymes. 
These  are  present  to  an  almost  negligible  extent  in  the  juices  of  the 
alimentary  canal,  and  have  been  studied  in  the  extracts  of  different 
organs ;  their  distribution  varies  a  good  deal  in  different  animals, 
and  in  the  different  organs  of  the  same  animal ;  speaking  generally, 
they  are  most  abundant  in  liver  and  spleen.  The  general  term 

2  ? 


594  THE  URINE  [CH.  XXXIX. 

nuclease  is  given  to  the  whole  group,  and  a  dozen  or  more  have 
been  isolated  which  deal  with  different  steps  in  the  cleavage  of  the 
nucleic  acid  complex.  They  are  classified  into  nucleinases  which 
resolve  the  molecule  into  mononucleotidases,  i.e.,  compounds  of  carbo- 
hydrate, phosphoric  acid,  and  one  base;  nucleotidases  which  liberate 
phosphoric  acid,  leaving  the  carbohydrate  still  united  to  the  base ; 
nucleosidases  which  hydrolytically  cleave  the  base  and  carbohydrate 
apart;  deamidases  which  remove  the  amino-group  from  the  purine 
bases  so  set  free ;  one  of  these,  called  adenase,  converts  adenine  into 
hypoxanthine,  and  another,  called  guanase,  converts  guanine  into 
xanthine.  Finally,  oxidases  step  in,  which  convert  hypoxanthine 
into  xanthine,  and  xanthine  into  uric  acid.  But  even  that  does  not 
bring  the  list  to  a  conclusion,  for  in  some  organs  (especially  the  liver) 
there  is  a  capacity  to  destroy  uric  acid  after  it  is  formed,  and  so  we 
are  protected  from  a  too  great  accumulation  of  this  substance. 
What  -exactly  happens  to  the  uric  acid  is  not  certain,  although  it  is 
clear  that  the  products  of  its  breakdown  (probably  allantoin  and 
urea)  are  not  so  harmful  as  uric  acid  itself.  The  enzyme  responsible 
for  uric  acid  destruction  is  called  the  uricolytic  enzyme.  The  uric 
acid  which  ultimately  escapes  as  urates  (normally)  in  the  urine  is 
the  undestroyed  residue. 

In  gout  and  allied  disorders  there  may  be  increased  formation  of 
uric  acid,  or  a  smaller  amount  of  that  formed  may  be  destroyed; 
the  excess  may  pass  into  the  urine,  partly  as  free  uric  acid  or  excess 
of  urates,  and  so  there  is  a  liability  to  concretions  (calculi,  gravel, 
etc.),  forming  in  the  kidney  or  bladder.  There  is  also  a  tendency 
to  the  deposition  of  urates  in  certain  parts,  and  the  joint  cartilages 
in  particular  are  liable  to  these  concretions.  The  uric  acid  diathesis 
is,  however,  much  too  large  a  subject  to  treat  in  a  physiological  text- 
book, and  medical  students,  when  they  come  to  the  study  of 
pathology,  will  discover  that  many  views  are  held  in  relation  to  it. 

Hippuric  Acid. 

Hippuric  Acid  (C9H9N03),  combined  with  bases  to  form  hip- 
purates,  is  present  in  small  quantities  in  human  urine,  but  in  large 
quantities  in  the  urine  of  herbivora.  This  is  due  to  the  food  of 
herbivora  containing  substances  belonging  to  the  aromatic  group — 
the  benzoic  acid  series.  If  benzoic  acid  is  given  to  a  man,  it  unites 
with  glycine  with  the  elimination  of  a  molecule  of  water,  and  is 
excreted  as  hippuric  acid — 

CH2.NH2     CH2NH.CO.CfiH, 

C6H6.COOH    +|  .  =  |  +    H2Q 

COOH         COOH 

[Benzoic  acid.]  [Glycine.]  [Hippuric  acid.]  [Water.] 

This  is  a  well-marked  instance  of  synthesis  carried  out  in  the 


CH.  XXXIX.]  SALTS   OP   URINE  595 

animal  body,  and  experimental  investigation  shows  that  it  is  accom- 
plished by  the  living  cells  of  the  kidney  itself;  for  if  a  mixture  of 
glycine,  benzole  acid,  and  blood  is  injected  through  the  kidney  (or 
mixed    with    a    minced    kidney    just 
removed  from  the  body  of  an  animal), 
their  place  is  found  to  have  been  taken 
by  hippuric  acid.     In  the  conversion 
of   benzoic  into   hippuric   acid   which 
occurs    in     herbivora,    the    necessary 
glycine  comes  from  the  kidney  itself. 


The  Inorganic  Constituents  of 
Urine. 

The  inorganic  or  mineral  constitu- 
ents   of    urine    are   chiefly   chlorides, 
phosphates,  sulphates,  and  carbonates;        FIG.  sss.— crystals  of  hippuric  acid. 
the  metals   with   which   these  are  in 

combination  are  sodium,  potassium,  ammonium,  calcium,  and  mag- 
nesium. The  total  amount  of  these  salts  varies  from  19  to  25 
grammes  daily.  The  most  abundant  is  sodium  chloride,  which 
averages  in  amount  10  to  16  grammes  per  diem.  These  substances 
are  derived  from  two  sources — first  from  the  food,  and  secondly  as 
the  result  of  metabolic  processes.  The  chlorides  and  most  of  the 
phosphates  come  from  the  food ;  the  sulphates  and  some  of  the  phos- 
phates, as  a  result  of  metabolism. 

Chlorides. — The  chief  chloride  is  that  of  sodium.  The  ingestion 
of  sodium  chloride  is  followed  by  its  appearance  in  the  urine, 
some  on  the  same  day,  some  on  the  next  day.  Some  is  decom- 
posed to  form  the  hydrochloric  acid  of  the  gastric  juice.  The  salt 
in  the  body  fulfils  the  useful  office  of  stimulating  metabolism  and 
secretion. 

Sulphates. — The  sulphates  in  the  urine  are  principally  those  of 
potassium  and  sodium.  Only  the  smallest  trace  enters  the  body  with 
the  food.  Sulphates  have  an  unpleasant  bitter  taste  (for  instance, 
Epsom  salts) :  hence  we  do  not  take  food  that  contains  them.  The 
sulphates  vary  in  amount  from  1*5  to  3  grammes  daily. 

They  are  derived  from  the  metabolism  of  proteins,  and  the 
excretion  of  sulphates,  though  it  occurs  earlier  than  that  of  urea, 
runs  parallel  with  it.  The  sulphates  are,  therefore,  like  urea,  the 
result  of  exogenous  protein  metabolism.  The  sulphur  of  the  protein, 
which  is  endogenously  katabolised,  is  not  converted  into  ordinary 
sulphates  to  any  great  extent,  but  reappears  in  the  urine  partly  as 
ethereal  sulphates,  and  partly  as  certain  obscure  but  not  fully  oxidised 
sulphur  compounds,  and  is  usually  spoken  of  as  neutral  sulphur. 


596  THE  URINE  [CH.  XXXIX. 

The  ethereal  sulphates  just  mentioned  form  about  a  tenth  of  the 
total  sulphates.  They  are  combinations  of  sulphuric  acid  with 
organic  radicals,  and  the  greater  part  of  them  originate  from  putre- 
factive changes  in  the  intestine.  The  chief  of  these  ethereal 
sulphates  are  phenyl  sulphate  of  potassium  and  indoxyl  sulphate  of 
potassium.  The  latter  originates  from  the  indole  formed  in  the 
intestine,  and  as  it  yields  indigo  when  treated  with  certain  reagents 
it  is  sometimes  called  indican.  The  indican  of  urine,  however,  is 
not  the  same  thing  as  the  indican  of  plants,  which  is  a  glucoside. 
Both  yield  indigo,  but  there  the  resemblance  ceases. 

The  formation  of  these  sulphates  is  somewhat  important;  the 
aromatic  substances  liberated  by  putrefactive  processes  in  the 
intestine  are  poisonous,  but  their  conversion  into  ethereal  sulphates 
renders  them  harmless. 

The  equation  representing  the  formation  of  potassium  phenyl-sulphate  is  as 
follows  :  — 


C6H5OH  +  S02  =  S02<65  +  H20. 

[Phenol.]  [Potassium  [Potassium  [Water.] 

hydrogen        phenyl-sulphate.] 
sulphate.] 

Indole  (C8H7N)  on  absorption  is  converted  into  indoxyl  :  — 

C.OH  :  CH 


The  equation  representing  the  formation  of  potassium  indoxyl-sulphate  is  as 
follows  :— 


C8H7NO  +  SO  :=  S02<8e      +  H20. 


[Indoxyl.]  [Potassium  [Potassium  [Water.] 

hydrogen  indoxyl-sulphate.] 

sulphate.] 

Carbonates.  —  Carbonates  and  bicarbonates  of  sodium,  calcium, 
magnesium,  and  ammonium  are  only  present  in  alkaline  urine. 
They  arise  from  the  carbonates  of  the  food,  or  from  vegetable  acids 
(malic,  tartaric,  etc.)  in  the  food.  They  are,  therefore,  found  in  the 
urine  of  herbivora  and  vegetarians,  whose  urine  is  thus  rendered 
alkaline.  Urine  containing  carbonates  becomes,  like  saliva,  cloudy 
on  standing,  the  precipitate  consisting  of  calcium  carbonate,  and 
also  phosphates. 

Phosphates.  —  Two  classes  of  phosphates  occur  in  normal  urine  :  — 

(1)  Alkaline  phosphates  —  that  is,  phosphates  of  sodium  (abundant) 
and  potassium  (scanty). 

(2)  Earthy  phosphates  —  that  is,  phosphates  of  calcium  (abundant) 
and  magnesium  (scanty). 

The  composition  of  the  phosphates  in  urine  is  liable  to  variation. 
In  acid  urine  the  acidity  is  due  to  the  acid  salts.  The  chief  are  :  — 

Sodium  dihydrogen  phosphate,  NaH9P04,  and  calcium  dihydrogen 
phosphate,  Ca(H2P04)2. 


CH.  XXXIX.]  SALTS   OF   URINE  597 

In  neutral  urine,  in  addition,  disodium  hydrogen  phosphate, 
Na2HP04,  calcium  hydrogen  phosphate,  CaHP04,  and  magnesium 
hydrogen  phosphate,  MgHP04,  are  found.  In  alkaline  urine  there 
may  be  instead  of,  or  in  addition  to,  the  above,  the  normal  phosphates 
of  sodium,  calcium,  and  magnesium  [Na3P04,  Ca3(P04)2,  Mg3(P04)2]. 

The  earthy  phosphates  are  precipitated  by  rendering  the  urine 
alkaline  by  ammonia.  In  decomposing  urine,  ammonia  is  formed 
from  the  urea:  this  also  precipitates  the  earthy  phosphates.  The 
phosphates  most  frequently  found  in  the 
white  creamy  precipitate  which  occurs 
in  decomposing  urine  are : — 

(1)  Triple   phosphate   or   ammonio- 
magnesium    phosphate    (NH4MgP04  + 
6H20).     This  crystallises  in  "  coffin-lid  " 
crystals  (see  fig.  384)  or  feathery  stars. 

(2)  Stellar    phosphate,    or    calcium 
phosphate ;  this  crystallises  in  star-like 
clusters  of  prisms. 

As  a  rule  normal  urine  gives  no 
precipitate  when  it  is  boiled ;  but  some- 
times neutral,  alkaline,  and  Occasionally 

faintly  acid  urines  give  a  precipitate  of 

Calcium     phosphate     When     boiled  :      this  JJ        undergone  alkaline  fer- 

precipitate  is  amorphous,  and  is  liable 
to  be  mistaken  for  albumin.  It  may  be  distinguished  readily  from 
albumin,  as  it  is  soluble  in  a  few  drops  of  acetic  acid,  whereas 
coagulated  protein  does  not  dissolve. 

The  phosphoric  acid  in  the  urine  chiefly  originates  from  the  phos- 
phates of  the  food,  but  is  partly  a  decomposition  product  of  the  phos- 
phorised  organic  materials  in  the  body,  such  as  lecithin  and  nuclein. 
The  amount  of  P205  in  the  twenty-four  hours'  urine  varies  from  2 '5 
to  3*5  grammes,  of  which  the  earthy  phosphates  contain  about  half 
(1  to.1'5  gr.).  The  urine  also  contains  minute  quantities  of  organic 
phosphates,  for  instance,  glycero-phosphates. 

Tests  for  the  Inorganic  Salts  of  Urine. 

Chlorides. — Acidulate  with  nitric  acid  and  add  silver  nitrate  ;  a  white  precipitate 
of  silver  chloride,  soluble  in  ammonia",  is  produced.  The  object  of  acidulating  with 
nitric  acid  is  to  prevent  phosphates  being  precipitated  by  the  silver  nitrate. 

Sulphates.  —Acidulate  with  hydrochloric  acid,  and  add  barium  chloride.  A 
white  precipitate  of  barium  sulphate  is  produced.  Hydrochloric  acid  is  again  added 
first,  to  prevent  precipitation  of  phosphates. 

Phosphates. — i.  Add  ammonia;  a  white  crystalline  precipitate  of  earthy  (that 
is,  calcium  and  magnesium)  phosphates  is  produced.  This  becomes  more  apparent 
on  standing.  The  alkaline  (that  is,  sodium  and  potassium)  phosphates  remain  in 
solution,  ii.  Mix  another  portion  of  urine  with  half  its  volume  of  nitric  acid  ;  add 
ammonium  molybdate,  and  boil.  A  yellow  crystalline  precipitate  falls.  This  test  is 
given  by  both  classes  of  phosphates. 


598  THE  URINE  [CH.  XXXIX. 

Quantitative  estimation  of  the  salts  is  accomplished  by  the  use  of  solutions  of 
standard  strength,  which  are  run  into  the  urine  till  the  formation  of  a  precipitate 
ceases.  The  standards  are  made  of  silver  nitrate,  barium  chloride,  and  uranium 
nitrate  or  acetate  for  chlorides,  sulphates,  and  phosphates  respectively. 

Urinary  Deposits. 

The  different  substances  that  may  occur  in  urinary  deposits  are 
formed  elements  and  chemical  substances. 

The  formed  or  anatomical  elements  may  consist  of  blood- 
corpuscles,  pus,  mucus,  epithelium  cells,  spermatozoa,  casts  of  the 
urinary  tubules,  fungi,  and  entozoa.  All  of  these,  with  the  exception 
of  a  small  quantity  of  mucus,  which  forms  a  flocculent  cloud  in  the 
urine,  are  pathological,  and  the  microscope  is  chiefly  employed  in 
their  detection. 

The  chemical  substances  are  uric  acid,  urates,  calcium  oxalate, 
calcium  carbonate,  and  phosphates.  Earer  forms  are  leucine,  tyrosine, 
xan thine,  and  cystine.  We  shall,  however,  here  only  consider  the 
commoner  deposits,  and  for  their  identification  the  microscope  and 
chemical  tests  must  both  be  employed. 

Deposit  of  Uric  Acid. — This  is  a  sandy  reddish  deposit  resembling 
cayenne  pepper.  It  may  be  recognised  by  its  crystalline  form  (fig. 
382,  p.  591)  and  by  the  murexide  reaction.  The  presence  of  these 
crystals  generally  indicates  an  increased  formation  of  uric  acid,  and,  if 
excessive,  may  lead  to  the  formation  of  stones  or  calculi  in  the  bladder. 

Deposit  of  Urates. — This  is  much  commoner,  and  may,  if  the 
urine  is  concentrated,  occur  in  normal  urine  when  it  cools.  It  is 
generally  found  in  the  concentrated  urine  of  fevers;  and  there 
appears  to  be  a  kind  of  fermentation,  called  the  acid  fermentation, 
which  occurs  in  the  urine  after  it  has  been  passed,  and  which  leads 
to  the  same  result.  The  chief  constituent  of  the  deposit  is  the  acid 
sodium  urate,  the  formation  of  which  from  the  normal  sodium  urate 
of  the  urine  may  be  represented  by  the  equation : — 

2C6H2Na2N4O8    +    H2O    +    CO,    =  =    2C5H3NaN4O3    +    Na2CO3. 

[Normal  sodium  [Water.]       [Carbonic        [Acid  sodium  urate.]  [Sodium 

urate.]  acid.]  %  carbonate.] 

This  deposit  may  be  recognised  as  follows : — 

(1)  It  has  a  pinkish  colour ;  the  pigment  called  uro-erythrin  is  one 
of  the  pigments  of  the  urine,  but  its  relationship  to  the  other  urinary 
pigments  is  not  known. 

(2)  It  dissolves  upon  warming  the  urine. 

(3)  Microscopically  it  is  usually  amorphous,  but  crystalline  forms 
similar  to  those  depicted  in  fig.  384  may  occur.     Crystals  of  calcium 
oxalate  may  be  mixed  with  this  deposit  (see  fig.  385). 

Deposit  of  Calcium  Oxalate. — This  occurs  in  envelope  crystals 
(octahedra)  or  dumb-bells.  It  is  insoluble  in  ammonia,  and  in  acetic 


CH.  XXX1X.J  URINARY   DEPOSITS  599 

acid.     It   is  soluble  with  difficulty  in  hydrochloric  acid.     Calcium 
oxalate  calculi  are  the  commonest  kind  of  stones  in  the  kidney. 


FIG.  335. — Crystals  of  calcium  oxalate.  FIG.  386. — Crystals  of  cystin. 

Deposit  of  Cystine. — Cystine  (C6H12N2S204)  is  recognised  by  its 
colourless  six-sided  crystals  (fig.  386).  These  are  rare:  they  occur 
only  in  acid  urine,  and  they  may  form  concretions  or  calculi. 
Cystinuria  (cystine  in  the  'urine)  is  hereditary. 

Deposit  of  Phosphates. — These  occur  in  alkaline  urine.  The 
urine  may  be  alkaline  when  passed,  due  to  fermentative  changes 
occurring  in  the  bladder.  All  urine,  however,  if  exposed  to  the  air 
(unless  the  air  is  perfectly  pure,  as  on  the  top  of  a  snow  mountain), 
will  in  time  become  alkaline,  owing  to  the  growth  of  the  micrococcus 
urece.  This  forms  ammonium  carbonate  from  the  urea. 

CON2H4   +    2H20    ..   (NH4)2C03. 

[Urea.]  [Water.]  [Ammonium 

carbonate.] 

The  ammonia  renders  the  urine  alkaline  and  precipitates  the 
earthy  phosphates.  The  chief  forms  of  phosphates  that  occur  in 
urinary  deposits  are — 

(1)  Calcium  phosphate,  Ca3(P04)2;  amorphous. 

(2)  Triple  or  ammonio-magnesium  phosphate,  MgNH4P04 ;  coffin- 
lids  and  feathery  stars  (fig.  384). 

(3)  Crystalline   phosphate   of   calcium,  CaHP04,  in   rosettes   of 
prisms,  in  spherules,  or  in  dumb-bells. 

(4)  Magnesium  phosphate,  Mg3(PQ4)2  +  22H20,  occurs  occasion- 
ally, and  crystallises  in  long  plates. 

All  these  phosphates  are  dissolved  by  acids,  such  as  acetic  acid, 
without  effervescence. 

A  solution  of  ammonium  carbonate  (1  in  5)  eats  magnesium 
phosphate  away  at  the  edges ;  it  has  no  effect  on  the  triple  phosphate. 
A  phosphate  of  calcium  (CaHP04  +  2H20)  may  occasionally  be 


600 


THE   URINE 


[CH.  XXXIX. 


deposited  in  acid  urine.  Pus  in  urine  is  apt  to  be  mistaken  for 
phosphates,  but  can  be  distinguished  by  the  microscope. 

Deposit  of  calcium  carbonate,  CaC03,  appears  but  rarely  as 
whitish  balls  or  biscuit-shaped  bodies.  It  is  commoner  in  the  urine 
of  herbivora.  It  dissolves  in  acetic  or  hydrochloric  acid,  with 
effervescence. 

The  following  is  a  summary  of  the  chemical  sediments  that  may 


occur  in  urine : — 


CHEMICAL  SEDIMENTS  IN  URINE. 


IN  ACID  URINE. 

Uric  Acid.—  Whetstone,  dumb-bell, 
or  sheaf-like  aggregations  of  crystals 
deeply  tinged  by  pigment. 

Urates.—  Generally  amorphous.  The 
acid  urate  of  sodium  and  of  ammonium 
may  sometimes  occur  in  star-shaped 
clusters  of  needles  or  spheroidal  clumps 
with  projecting  spines.  Tinged  brick- 
red.  Soluble  on  warming. 

Calcium  Oxalate.  —  Octahedra,  so- 
called  envelope  crystals.  Insoluble  in 
acetic  acid. 

Cystine. — Hexagonal  plates.     Rare. 

Leucine  and  Tyrosine. — Rare. 

Calcium  Phosphate, 

CaHPO4  +  2H2O.— 


IN  ALKALINE  URINE. 

Phosphates.  —  Calcium  phosphate, 
Ca3(PO4)2.  Amorphous. 

Triple  phosphate, 

MgNH4PO4  +  6H2O.       Coffin-lids    or 
feathery  stars. 

Calcium  hydrogen  phosphate, 
CaHPO4.    Rosettes,  spherules,  or  dumb- 
bells. 

Magnesium  phosphate, 
Mg3(PO4)2  +  22H2O.     Long  plates. 

All  the  preceding  are  soluble  in  acetic 
acid  without  effervescence. 

Calcium  Carbonate,  CaCO3. — Biscuit- 
shaped  crystals.  Soluble  in  acetic  acid 
with  effervescence. 

Ammonium  Urate, 

C5H2(NH4)2.N4O3.    —  "  Thorn  -  apple  " 
spherules. 

Leucine  and  Tyrosine. — Very  rare. 


PATHOLOGICAL  URINE. 

Under  this  head  we  shall  briefly  consider  only  those  abnormal 
constituents  which  are  most  frequently  met  with. 

Proteins. — There  is  no  protein  in  normal  urine,*  and  the  most 
common  cause  of  the  appearance  of  albumin  in  the  urine  is  disease 
of  the  kidney  (Bright's  disease).  The  term  "albumin"  is  the  one 
used  by  clinical  observers.  Properly  speaking,  it  is  a  mixture  of 
serum  albumin  and  serum  globulin.  Of  these,  serum  albumin  is 
usually  the  more  abundant.  Globulins,  and  especially  euglobulins, 
have  probably  larger  molecules,  so  escape  of  globulin  indicates  more 
serious  damage  to  the  renal  cells.  The  best  methods  of  testing  for 
and  estimating  the  protein  are  the  following : — 

(a)  Boil  the  top  of  a  long  column  of  urine  in  a  test-tube.  If  the  urine  is  acid, 
the  albumin  is  coagulated.  If  the  quantity  of  albumin  is  small,  the  cloudiness 
produced  is  readily  seen,  as  the  unboiled  urine  below  it  is  clear.  This  is  insoluble 

*  This  absolute  statement  is  true  for  all  practical  purposes.  Morner,  however, 
has  stated  that  a  trace  of  protein  (serum  albumin  phis  the  protein  constituent  of 
mucin)  does  occur  in  normal  urine  ;  but  the  trace  is  negligible,  many  hundreds  of 
litres  of  urine  having  to  be  used  to  obtain  an  appreciable  quantity. 


CH.  XXXIX.]  ALBUMIN   AND   SUGAR   IN  URINE  601 

in  a  few  drops  of  acetic-  acid,  and  so  may  be  distinguished  from  phosphates. 
If  the  urine  is  alkaline,  it  should  be  first  rendered  acid  with  a  little  dilute 
acetic  acid. 

(6)  Heller's  Nitric-acid  Test. — Pour  some  of  the  urine  gently  on  to  the  surface 
of  some  nitric  acid  in  a  test-tube.  A  ring  of  white  precipitate  occurs  at  the 
junction  of  the  two  liquids.  This  test  is  used  for  small  quantities  of  albumin. 

(c)  Estimation  of  Albumin  by  E shack's  Albuminometer. — 
Esbach's  reagent  for  precipitating  the  albumin  is  made  by 
.dissolving  10  grammes  of  picric  acid  and  20  grammes  of  citric 
acid  in  800  or  900  c.c.  of  boiling  water,  and  then  adding  suffi- 
cient water  to  make  up  to  a  litre  (1000  c.c.). 

The  albuminometer  is  a  test-tube  graduated  as  shown  in 
fig.  387. 

Pour  the  urine  into  the  tube  up  to  the  mark  U ;  then  the 
reagent  up  to  the  mark  R.  Close  the  tube  with  a  cork,  and 
to  ensure  complete  mixture,  tilt  it  to  and  fro  a  dozen  times 
without  shaking.  Allow  the  corked  tube  to  stand  upright 
twenty- four  hours  ;  then  read  off  on  the  scale  the  height  of  the 
coagulum.  The  figures  indicate  grammes  of  dried  albumin  in 
a  litre  of  urine.  The  percentage  is  obtained  by  dividing  by  10. 
Thus,  if  the  coagulum  stands  at  3,  the  amount  of  albumin  is 
3  grammes  per  litre,  or  0'3  gr.  in  100  c.c. 

A  condition  called  "  peptonuria,"  or  peptone  in 
the  urine,  is  observed  in  certain  pathological  states, 
especially  in  diseases  where  there  is  a  formation  of 
pus,  and  particularly  if  the  pus  is  decomposed  owing 
to  the  action  of  bacterial  growths  such  as  staphy- 
lococcus:  one  of  the  products  of  disintegration  of 

j    , ,  .     *  , ,  FIG.  387.— Esbach's 

pus  cells  appears  to  be  peptone ;  and  this  leaves  the       Albuminometer. 
body  by  the  urine.     The  term  "peptone,"  however, 
is  in  the  strict  sense  of  the  word  incorrect ;  the  protein  present  is 
deutero-proteose.     In   certain   diseases   of  bone   a  curious   protein 
passes  into  the  urine.      It  is  called  Bence- Jones  protein,  after  its 
discoverer ;  it  somewhat  resembles  hetero-proteose  in  its  properties. 

Sugar. — Normal  urine  contains  no  sugar,  or  so  little  that  for 
clinical  purposes  it  may  be  considered  absent.  The  conditions  in 
which  glycosuria  occurs  are  described  on  p.  538. 

The  sugar  present  is  dextrose.  Lactose  may  occur  in  the  urine 
of  nursing  mothers.  Lsevulose,  pentoses,  and  other  sugars  are  found 
but  rarely.  Diabetic  urine  also  contains  hydroxybutyric  acid,  and 
may  contain  and  yield  on  distillation  acetone,  and  aceto-acetic  acid. 
The  methods  usually  adopted  for  detecting  and  estimating  the  sugar 
are  as  follows: — 


(a)  The  urine  has  generally  a  high  specific  gravity. 
(&) 


The  presence  of  sugar  is  shown  by  the  reduction  (yellow  precipitate  of 
cuprous  oxide)  that  occurs  on  boiling  with  Fehling's  solution.  Fehling's  solution  is 
an  alkaline  solution  of  copper  sulphate  to  which  Rochelle  salt  has  been  added.  The 
Rochelle  salt  (double  tartrate  of  potash  and  soda)  holds  the  cupric  hydrate  in 
solution.  Fehling's  solution  should  always  be  freshly  prepared,  as,  on  standing,  an 
isomeride  is  formed  from  the  tartaric  acid,  which  reduces  the  cupric  to  cuprous 
oxide.  Fehling's  solution  should,  therefore,  always  be  tested  by  boiling  before  it  is 
used.  If  it  remains  clear  on  boiling,  it  is  in  good  condition. 


602  THE  URINE  [CH.  XXXIX. 

(c)  Quantitative  Determination  of  Sugar  in  Urine. — Fehling's  solution  is  pre- 
pared as  follows:- 34*639  grammes  of  copper  sulphate  are  dissolved  in  about  200 
c.c.  of  distilled  water;  173  grammes  of  Rochelle  salt  are  dissolved  in  600  c.c.  of  a 
14  per  cent,  solution  of  caustic  soda.     The  two  solutions  are  mixed  and  diluted  to  a 
litre.     Ten  c.c.  of  this  solution  are  equivalent  to  0'05  gramme  of  dextrose.     Dilute 
10  c.c.  of  this  solution  with  about  40  c.c.  of  water,  and  boil  it  in  a  porcelain  basin. 
Run  into  this  from  a  burette  the  urine  (which  should  be  previously  diluted  with  nine 
times  its  volume  of  distilled  water)  until  the  blue  colour  of  the  copper  solution 
disappears— that  is,  till  all  the  cupric  hydrate  is  reduced.     The  mixture  in  the  basin 
should  be  boiled  after  every  addition.     The  quantity  of  diluted  urine  used  from  the 
burette  contains   0'05  gramme  of   sugar.     Calculate  the  percentage  from   this, 
remembering  that  the  urine  has  been  diluted  to  ten  times  its  original  volume. 

Pavy's  modification  of  Fehling's  solution  is  often  used.  Here  ammonia 
holds  the  copper  in  solution,  and  no  precipitate  forms  on  boiling  with  sugar,  as 
ammonia  holds  the  cuprous  oxide  in  solution.  The  reduction  is  complete  when  the 
blue  colour  disappears;  10  c.c.  of  Pavy's  solution  =  1  c.c.  of  Fehling's  solution  = 
0'005  gramme  of  dextrose. 

There  are  several  other  modifications  of  the  original  Fehling  method  which 
have  been  introduced  with  the  purpose  of  making  the  end-point  clearer.  Allihn's 
method  is  the  most  accurate  ;  the  cuprous  oxide  is  collected,  and  finally  reduced  to 
metallic  copper,  which  is  then  weighed. 

Fehling's  test  is  not  absolutely  trustworthy.  Often  a  normal  urine  will 
decolorise  Fehling's  solution,  though  seldom  a  red  precipitate  is  formed.  This  is 
due  to  excess  of  urates  and  creatinine.  Another  substance  called  glycuronic  acid 
(C6H10O7)  is,  however,  very  likely  to  be  confused  with  sugar  by  Fehling's  test ;  the 
cause  of  its  appearance  is  sometimes  the  administration  of  drugs  (chloral,  camphor, 
etc.) ;  but  sometimes  it  appears  independently  of  drug  treatment. 

In  the  rare  and  hereditary  condition  called  alcaptonuria,  confusion  may  also 
arise.  Alcapton  is  a  *  substance  which  originates  from  tyrosine  by  an  unusual 
form  of  metabolism.  It  gives  the  urine  a  brown  tint,  which  darkens  on  exposure 
to  the  air.  It  is  an  aromatic  substance,  which  Baumann  and  Wolkow  and  later 
Garrod  identified  with  homogentisic  acid  (C6H3.(OH),CH2.COOH). 

(d)  A  good  confirmatory  test  for  sugar  is  the  fermentation  test,  which  is  per- 
formed as  follows : — 

Half  fill  a  test-tube  with  the  urine  and  add  a  little  German  yeast.  Fill  up  the 
tube  with  mercury ;  invert  it  in  a  basin  of  mercury,  and  leave  it  in  a  warm  place 
for  twenty-four  hours.  The  sugar  will  undergo  fermentation :  carbonic  acid  gas 
accumulates  in  the  tube,  and  the  liquid  no  longer  gives  the  tests  for  sugar,  or  only 
faintly,  but  gives  those  for  alcohol  instead.  The  specific  gravity  falls. 

(e)  The  phenylhydrazine  test  (p.  412)  may  also  be  applied. 

Another  hereditary  abnormality  of  metabolism  is  pentosuria  ;  this  is  apt  to  be 
mistaken  for  diabetes,  for  pentose  reduces  Fehling's  solution,  but  it  will  not  ferment 
with  yeast.  It  is  a  rare  condition,  but  does  not  appear  to  do  any  harm.  The  source 
of  the  pentose  is  not  the  food,  for  pentosuria  continues  in  these  cases  when  the  food 
contains  no  pentose.  The  pentose  of  the  urine,  moreover,  is  a  different  one  from 
that  found  in  the  nucleic  acids  of  the  body.  Neuberg  thinks  it  arises  in  some  way 
from  galactose,  and  that  it  originates  from  the  galactosides  of  the  body. 

Bile. — This  occurs  in  jaundice.  The  urine  is  dark-brown, 
greenish,  or  in  extreme  cases  almost  black  in  colour.  The  most 
readily  applied  test  is  Gmelin's  test  for  the  bile  pigments.  Excess 
of  urobilin  should  not  be  mistaken  for  bile  pigment.  Pettenkofer's 
test  for  the  bile  acids  seldom  succeeds  in  urine  if  the  test  is  done  in 
the  ordinary  way.  The  best  method  is  to  warm  a  thin  film  of  urine 
and  cane  sugar  solution  in  a  flat  porcelain  dish.  Then  dip  a  glass  rod 
in  strong  sulphuric  acid,  and  draw  it  across  the  film.  Its  track  is 
marked  by  a  purplish  line.  Hay's  sulphur  test  is  a  good  one  for  bile 


CH.  XXXIX.]  BILE,   BLOOD,   AND   PUS   IN   UEINE  603 

salts.  If  some  ilowers  of  sulphur  are  sprinkled  on  the  surface  of 
normal  urine,  it  remains  floating  on  the  top.  If  bile  salts  are  present 
even  in  small  quantities,  the  fine  sulphur  particles  fall  down  to  the 
bottom  of  the  vessel  in  which  the  urine  is  contained ;  this  is  due  to 
an  alteration  of  surface  tension  which  bile  salts  produce. 

Blood. — When  haemorrhage  occurs  in  any  part  of  the  urinary 
tract,  blood  appears  in  the  urine.  It  is  found  in  the  acute  stage  of 
Bright's  disease.  If  a  large  quantity  is  present,  the  urine  is  deep 
red.  Microscopic  examination  then  reveals  the  presence  of  blood - 
corpuscles,  and  on  spectroscopic  examination  the  bands  of  oxyhaemo- 
globin  are  seen. 

If  only  a  small  quantity  of  blood  is  present,  the  secretion — 
especially  if  acid — has  a  characteristic  reddish-brown  colour,  which 
physicians  term  "  smoky." 

The  blood  pigment  may,  under  certain  circumstances,  appear  in 
the  urine  without  the  presence  of  any  blood-corpuscles  at  all.  This 
is  produced  by  a  disintegration  of  the  corpuscles  occurring  in  the 
circulation.  The  condition  so  produced  is  called  hcemogldbinuria ; 
it  occurs  in  several  pathological  states,  as  for  instance  in  the  tropical 
disease  called  "Black-water  fever."  The  pigment  is  in  the  condi- 
tion of  methaemoglobin  mixed  with  more  or  less  oxyhaemoglobin,  and 
the  spectroscope  is  the  means  used  for  identifying  these  substances. 

Pus  occurs  in  the  urine  as  the  result  of  suppuration  in  any  part 
of  the  urinary  tract.  It  forms  a  white  sediment  resembling  that  of 
phosphates,  and,  indeed,  is  always  mixed  with  phosphates.  The  pus 
corpuscles  may,  however,  be  seen  with  the  microscope ;  their  nuclei 
are  rendered  evident  by  treatment  with  1  per  cent,  acetic  acid,  and 
the  pus-corpuscles  are  seen  to  resemble  white  blood-corpuscles,  which, 
in  fact,  they  are  in  origin.  They  dissolve  in  glacial  acetic  acid. 

Some  of  the  protein  constituents  of  the  pus  cells — and  the  same 
is  true  for  blood — pass  into  solution  in  the  urine,  so  that  the  urine 
pipetted  off  from  the  surface  of  the  deposit  gives  the  tests  for  protein. 

On  the  addition  of  liquor  potassae  to  the  deposit  of  pus  cells,  a 
ropy  gelatinous  mass  is  obtained.  This  is  distinctive.  Mucus  treated 
in  the  same  way  is  dissolved. 

Amino-acids. — Normal  urine  contains  traces  of  glycine.  Leucine, 
tyrosine,  and  other  amino-acids  may  be  present  after  extensive  dis- 
integration of  tissue  protein,  such  as  occurs  in  acute  atrophy  of  the 
liver  (p.  586).  Cystine  may  occur  as  a  rare  anomaly  of  metabolism 
(p.  599).  Associated  with  cystinuria  one  often  finds  diaminuria, 
that  is,  the  passage  of  diamines  into  the  urine ;  these  are  known  as 
cadaverine  (C5H14N2)  and  putrescine  (C4H1:>N2),  and  are  the  result  of 
the  removal  of  CO2  from  the  diamino-acids  lysine  and  01  nithine  respect- 
ively. Homogentisic  acid,  found  in  alcaptonuria  (see  preceding  page), 
is  another  somewhat  similar  anomaly ;  it  arises  from  tyrosine. 


CHAPTER  XL 

THE  SKIN  AND   ITS   APPENDAGES 

THE  skin  is  composed  of  two  parts,  epidermis  or  cuticle,  and  dermis 
or  cutis  vera. 

The  Epidermis  is  a  thick  stratified  epithelium.  The  deeper 
layers  are  composed  of  protoplasmic  cells,  and  form  the  rete  mucosum, 
or  Malpighian  layer;  the  surface  layers  are  hard  and  horny;  this 
horny  layer  is  the  thickest  part  of  the  epidermis,  and  is  specially 
thick  on  the  palms  and  soles,  where  it  is  subjected  to  most  friction. 
It  is  in  the  cells  of  the  Malpighian  layer  that  pigment  granules  are 
deposited  in  the  coloured  races. 

Between  the  horny  layer  and  the  Malpighian  layer  are  two 
intermediate  strata,  in  which  the  transformation  of  protoplasm  into 
horny  material  (keratin)  is  taking  place.  In  the  first  of  these — that 
is,  the  one  next  to  the  Malpighian  layer — the  cells  are  flattened, 
and  filled  with  large  granules  of  eleidin,  an  intermediate  substance 
in  the  formation  of  horn.  This  layer  is  called  the  stratum 
granulosum. 

Above  this  are  several  layers  of  clear,  more  rounded  cells,  which 
constitute  the  stratum  lucidum;  and  above  this  the  horny  layer 
proper,  many  strata  deep,  begins.  The  cells  become  more  and  more 
scaly  as  they  approach  the  surface,  where  they  lose  their  nuclei  and 
eventually  become  detached. 

The  epidermis  grows  by  a  multiplication  of  the  deepest  layer  of 
cells;  the  newly-formed  cells  push  towards  the  surface  those  pre- 
viously formed,  in  their  progress  undergoing  the  transformation  into 
keratin. 

The  epidermis  has  no  blood-vessels;  nerve-fibrils  pass  into  its 
deepest  layers,  and  ramify  between  the  cells. 

The  Dermis  is  composed  of  dense  fibrous  tissue,  which  becomes 
looser  and  more  reticular  in  its  deeper  part,  where  it  passes  by 
insensible  degrees  into  the  areolar  and  adipose  tissue  of  the  sub- 
cutaneous region.  The  denser  superficial  layer  is  very  vascular,  and 
is  covered  with  minute  papilla ;  the  epidermis  is  moulded  over  these, 

604 


CH.  XL.] 


THE  SKIN 


605 


and  in  the  palms  and  soles,  where 
disposed  in  rows,  their  presence 
is  indicated   by  the  well-known 
ridges  on  the  surface. 

The  papillse  contain  loops  of 
capillaries,  and  in  some  cases, 
especially  in  the  palm  of  the 
hand  and  fingers,  they  contain 
tactile  corpuscles  (which  will  be 
more  fully  described  in  connec- 
tion with  the  sense  of  touch). 
Special  capillary  networks  are 
distributed  to  the  sweat-glands, 
sebaceous  glands,  and  hair  fol- 
licles. 

The  deeper  portions  of  the 
dermis  in  the  scrotum,  penis, 
and  nipple,  contain  involuntary 
muscular  tissue;  there  is  also  a 
bundle  of  muscular  tissue  at- 
tached to  each  hair  follicle. 

The  Nails  are  thickenings  of 
the  stratum  lucidum.  Each  lies 
in  a  depression  called  the  led  of 
the  nail,  the  posterior  part  of 
which  is  overlapped  by  epidermis, 
and  called  the  nail-groove.  The 
dermis  beneath  is  beset  with 
longitudinal  ridges  instead  of 
papillse ;  these  are  very  vascular ; 
but  in  the  lunula,  the  crescent  at 
the  base  of  the  nail,  there  are 
papillse,  and  this  part  is  not  so 
vascular. 

The  Hairs  are  epidermal 
growths,  contained  in  pits  called 
hair  follicles.  The  part  within 
the  follicle  is  called  the  root  of 
the  hair. 

The  main  substance  of  the 
hair  is  composed  of  pigmented 
horny  fibrous  material,  in  reality 
long  fibrillated  cells.  It  is  covered 
by  a  layer  of  scales  imbricated 
upwards  (hair  cuticle).  In  many 


the  papillae  are  largest  and  are 


< 


^  v 


FIG.  388.— Vertical  section  through  the  skin  of  tho 
sole  of  the  foot,  a,  Horny  layer ;  b,  stratum 
granulosum;  c,  stratum  lucidum;  d,  Mal- 
pighian  layer ;  e,  cutis  vera ;  /,  papilla  of 
cutis  vera ;  g,  fat  lobule  of  subcutaneous 
tissue;  h,  sweat-gland;  i,  orifice  of  sweat- 
duct.  (Szymonowicz.) 


606 


THE  SKIN   AND   ITS   APPENDAGES 


[CH.  XL. 


hairs  the  centre  is  occupied  by  a  medulla,  formed  of  rounded  cells 
containing  eleidin  granules.  Minute  air-bubbles  may  be  present  in 
both  medulla  and  fibrous  layer,  and  cause  the  hair  to  look  white  by 


*  C 


reflected  light.  The  grey  hair 
of  old  age,  however,  is  pro- 
duced by  a  loss  of  pigment. 

The  root  is  enlarged  at  its 
extremity    into    a    knob,    into 
which  projects  a  vascular  papilla  from 
the  true  skin. 

The  hair  follicle  consists  of  two 
parts,  one  continuous  with  the  epi- 
dermis, called  the  root-sheath,  the  other 
continuous  with  the  dermis,  called  the 
dermic  coat.  The  two  are  separated 
by  a  basement  membrane  called  the 
hyaline  layer  of  the  follicle.  The  root- 
sheath  consists  of  an  outer  layer  of 

cells  like  the  Malpighian  layer  of  the  epidermis,  with  which  it  is 
directly  continuous  (outer  root-sheath),  and  of  an  inner  horny  layer 
(inner  root-sheath},  continuous  with  the  horny  layer  of  the  epidermis. 
The  inner  root-sheath  consists  of  three  layers,  the  outermost  being 
composed  of  long,  non-nucleated  cells  (Henle's  layer),  the  next  of 
squarish  nucleated  cells  (Huxley's  layer),  and  the  third  is  a  cuticle  of 


FIG.  389.— Vertical  section  of  skin. 
A.  Sebaceous  gland  opening 
into  hair  follicle.  B.  Muscu- 
lar fibres.  C.  Sudoriferous  or 
sweat-gland.  D.  Subcutaneous 
fat.  E.  Fundus  of  hair  follicle, 
with  hair  papilla.  (Klein.) 


CH.  XL.] 


THE   HAIRS 


607 


scales,  imbricated  downwards,  which  fit  over  the  scales  of  the  cuticle 
of  the  hair  itself. 


FIG.    390. — Longitudinal    section   of  a 
hair  follicle,   a  and  b,  External  root- 
sheath  ;    c,    internal    root-sheath ; 
d,  fibrous  layer  of  the  hair ;  e,  me-          PlO-  391.— Transverse  section  of  a  hair  and  hair  follicle 
dulla;  /,   hair  papilla;    g,   blood-  made    below  the    opening   of  the    sebaceous    gland, 

vessels   of    the   hair   papilla;    h,  «.  Medulla,  or  pith  of  the  hair;    b,  fibrous  layer; 

uermic  coat.    (Cadiat.)  c,  cuticle;    d,   Huxley's   layer;    c,   Henle's    layer   of 

internal  root-sheath  ;  /  and  g,  layers  of  external  root- 
sheath,  outside  of  g  is  the  basement  membrane  or 
hyaline  layer ;  h,  dermic  (fibrous)  coat  of  hair  follicle ; 
i,  vessels.  (Cadiat.) 

A  small  bundle  of  plain  muscular  fibres  is  attached  to  each 
follicle  (fig.  389).  When  it  contracts,  as  under  the  influence  of  cold, 
or  of  certain  emotions  such  as  fear, 
the  hair  is  erected  and  the  whole 
skin  is  roughened  ("  goose  skin  "). 
The  nerves  supplying  these  muscles 
are  called  pilo-motor  nerves.  The 
distribution  of  these  nerves  closely 
follows  those  of  the  vaso-constrictor 
nerves  of  the  skin;  their  cell-sta- 
tions are  in  the  lateral  sympathetic 
chain. 

The  sensitiveness  of  the  hairs  or 
more  properly  of  the  hair  follicles 
is  subserved  by  a  ring-like  plexus  Fl 
of  nerve-fibrils  around  the  hair 
follicle,  within  the  outer  sheath, 
just  beneath  the  entrance  of  the  sebaceous  gland  (see  fig.  392). 


392. — Sensory  nerve  ending  of  hair  fol- 
licle. Gold  chloride;  preparation.  x  900. 
(Szymonowicz.) 


608  THE   SKIN   AND    ITS    APPENDAGES  [CH.  XL. 

The  sebaceous  glands  (fig.  389)  are  small  saccular  glands,  with 
ducts  opening  into  the  upper  portion  of  the  hair  follicles.  The 
secreting  cells  become  charged  with  fatty  matter,  which  is  discharged 
into  the  lumen  of  the  saccules  owing  to  the  disintegration  of  the  cells. 
The  secretion,  sebum,  contains  isocholesterin  (see  p.  436)  in  addition 
to  fatty  matter.  It  acts  as  a  lubricant  to  the  hairs. 

The  sweat-glands  (fig.  388)  are  abundant  over  the  whole  human 
skin,  but  are  most  numerous  where  hairs  are  absent,  on  the  palms 
and  soles.  Each  consists  of  a  coiled  tube  in  the  deepest  part  of  the 
dermis,  the  duct  from  which  passes  up  through  the  dermis,  and  by  a 
corkscrew-like  canal  through  the  epidermis  to  the  surface. 

The  secreting  tube  is  lined  by  one  or  two  layers  of  cubical  or 
columnar  cells;  outside  this  is  a  layer  of  longitudinally  arranged 
muscular  fibres,  and  then  a  basement  membrane. 

The  duct  is  of  similar  structure,  except  that  there  is  usually  but 
one  layer  of  cubical  cells,  and  muscular  fibres  are  absent ;  the  passage 
through  the  epidermis  has  no  proper  wall ;  it  is  merely  a  channel 
excavated  between  the  epidermal  cells. 

The  ceruminous  glands  of  the  ear  are  modified  sweat-glands. 

THE  FUNCTIONS  OF  THE  SKIN 

Protection. — The  skin  acts  as  a  protective  organ,  not  only  by 
mechanically  covering  and  so  defending  internal  structures  from 
external  violence,  but  more  particularly  in  virtue  of  its  being  an  organ 
of  sensation  (see  later  in  the  chapter  on  Touch). 

Heat  Regulation. — See  chapter  on  Temperature. 

Respiration. — A  small  amount  of  respiratory  interchange  of  gases 
occurs  through  the  skin,  but  in  thick-skinned  animals  this  is  very 
small.  In  man,  the  carbonic  acid  exhaled  by  the  skin  is  about  T^o- 
to  2ihr  of  that  which  passes  from  the  lungs.  But  in  thin-skinned 
animals,  such  as  frogs,  cutaneous  respiration  is  very  important ;  after 
the  removal  of  the  lungs  of  a  frog,  the  respiratory  interchange  through 
the  skin  is  sufficient  to  keep  the  animal  alive,  the  amount  of  carbonic 
acid  discharged  being  about  half  as  much  as  when  the  lungs  are 
present  (Bischoff). 

Absorption. — This  also  is  an  unimportant  function ;  but  the  skin 
will  in  a  small  measure  absorb  oily  materials  placed  in  contact  with 
it ;  thus  in  some  cases  infants  who  will  not  take  cod-liver  oil  by  the 
mouth,  can  yet  be  dosed  with  it  by  rubbing  it  into  the  skin.  Many 
ointments  also  are  absorbed,  and  thus  general  effects  are  produced  by 
local  inunction. 

Secretion. — The  secretions  of  the  skin  are  two  in  number.  The 
sebum  is  the  natural  lubricant  of  the  hairs.  The  secretion  of  sweat  is 
an  important  function  of  the  skin,  and  we  will  therefore  discuss  it  at 
greater  length. 


CH.  XL.]  THE  SWEAT  609 

THE  SWEAT 

Physiology  of  the  Secretion  of  Sweat. — We  have  seen  that  the 
sweat-glands  are  most  abundant  in  man  on  the  palms  and  soles,  and 
here  the  greatest  amount  of  perspiration  occurs.  Different  animals 
vary  a  good  deal  in  the  amount  of  sweat  they  secrete,  and  in  the 
place  where  the  secretion  is  most  abundant.  Thus  the  ox  perspires 
less  than  the  horse  and  sheep;  perspiration  is  absent  from  rats, 
rabbits,  and  goats ;  pigs  perspire  mostly  on  the  snout ;  dogs  and  cats 
on  the  pads  of  the  feet. 

As  long  as  the  secretion  is  small  in  amount,  it  is  evaporated  from 
the  surface  at  once ;  this  is  called  insensible  perspiration.  As  soon  as 
the  secretion  is  increased  or  evaporation  prevented,  drops  appear  on 
the  surface  of  the  skin.  This  is  known  as  sensible  perspiration.  The 
relation  of  these  two  varies  with  the  temperature  of  the  air;  the 
drier  and  hotter  the  air,  the  greater  is  the  proportion  of  insensible 
to  sensible  perspiration.  In  round  numbers  the  total  amount  of 
sweat  secreted  by  a  man  is  two  pounds  in  the  twenty-four  hours. 

The  amount  of  secretion  is  influenced  by  the  vaso-motor  nerves ; 
an  increase  in  the  size  of  the  skin-vessels  leads  to  increased,  a  con- 
striction of  the  vessels  to  diminished,  perspiration.  There  are  also 
special  secretory  fibres,  stimulation  of  which  causes  a  secretion  even 
when  the  circulation  is  suspended,  as  in  a  recently  amputated  limb. 
These  fibres  are  paralysed  by  atropine.  They  are  contained  in  the 
same  nerve-trunks  as  the  vaso-motor  nerves,  as  are  also  the  nerve- 
fibres  which  supply  the  plain  muscular  fibres  of  the  sweat-glands 
which  act  during  the  expulsion  of  the  secretion.  The  secretory 
nerves  for  the  lower  limbs  issue  from  the  spinal  cord  by  the  last  two 
or  three  dorsal  and  first  two  or  four  lumbar  nerves  (in  the  cat) ;  they 
have  cell-stations  in  the  lower  ganglia  of  the  lateral  chain,  and  pass 
thence  to  the  sciatic  nerve.  They  are  controlled  by  a  centre  in  the 
upper  lumbar  region  of  the  cord ;  those  for  the  upper  limbs  leave  the 
cord  by  the  sixth,  seventh,  and  eighth  anterior  thoracic  roots,  have 
cell-stations  in  the  ganglion  stellatum,  and  ultimately  pass  to  the 
ulnar  and  median  nerves;  they  are  controlled  by  a  centre  in  the 
cervical  enlargement  of  the  cord.  The  secretory  fibres  for  the  head 
pass  in  the  cervical  sympathetic,  and  in  some  branches  of  the  fifth 
cranial  nerves.  These  subsidiary  centres  are  dominated  by  one  in 
the  medulla  oblongata  (Adamkiewicz).  These  facts  have  been 
obtained  by  experiments  on  animals  (cat,  horse). 

The  sweat-centres  may  be  excited  directly  by  venous  blood,  as  in 
asphyxia ;  or  by  over -heated  blood  (over  45°  C.) ;  or  by  certain  drugs 
(see  further) ;  or  reflexly  by  stimulation  of  afferent  nerves  such  as 
the  crural  and  peroneaL 

Nervous  diseases  are  often  accompanied  with  disordered  sweating ; 

2  Q 


610  THE   SKIN   AND   ITS    APPENDAGES  [CH.  XL. 

thus  unilateral  perspiration  is  sometimes  seen  in  cases  of  hemi- 
plegia;  degeneration  of  the  anterior  nerve-cells  of  the  cord  may 
cause  stoppage  of  the  secretion. 

The  changes  that  occur  in  the  secreting  cells  have  been  investi- 
gated by  Eenaut  in  the  horse.  When  charged  they  are  clear 
and  swollen,  the  nucleus  being  situated  near  their  attached  ends; 
when  discharged  they  are  smaller,  granular,  and  their  nucleus  is 
more  central. 

The  sweat,  like  the  urine,  must  be  regarded  as  an  excretion,  the 
secreting  cells  eliminating  substances  formed  elsewhere. 

Composition  of  the  Sweat. — Sweat  may  be  obtained  in  abundant 
quantities  by  placing  the  animal  or  man  in  a  closed  hot-air  bath,  or 
from  a  limb  by  enclosing  it  in  a  vessel  made  air-tight  with  an  elastic 
bandage.  Thus  obtained,  it  is  mixed  with  epidermal  scales  and  a 
small  quantity  of  fatty  matter  from  the  sebaceous  glands.  The  con- 
tinual shedding  of  epidermal  scales  is  in  reality  an  excretion. 
Keratin,  of  which  they  are  chiefly  composed,  is  rich  in  sulphur,  and, 
consequently,  this  is  one  means  by  which  sulphur  is  removed  from 
the  body. 

The  reaction  of  sweat  is  acid,  and  the  acidity,  as  in  the  urine,  is 
due  to  acid  sodium  phosphate.  In  profuse  sweating,  however,  the 
secretion  usually  becomes  alkaline  or  neutral.  It  has  a  peculiar 
and  characteristic  odour,  which  varies  in  different  parts  of  the  body, 
and  is  due  to  volatile  fatty  acids ;  its  taste  is  saltish,  its  specific 
gravity  about  1005. 

In  round  numbers  the  percentage  of  solids  is  1/2,  of  which  0'8 
is  inorganic  matter. 

The  salts  are  in  kind  and  relative  quantity  very  like  those  of  the 
urine ;  sodium  chloride  is  the  most  abundant  salt.  Funke  was  unable 
to  find  any  urea,  but  most  other  observers  agree  on  the  presence  of  a 
minute  quantity.  It  appears  to  become  quickly  transformed  into 
ammonium  carbonate.  The  protein  which  is  present  is  probably 
derived  from  the  epithelial  cells  of  the  epidermis,  sweat-glands, 
and  sebaceous  glands,  which  are  suspended  in  the  excretion;  but 
in  the  horse  there  is  albuminous  matter  actually  in  solution  in 
the  sweat. 

Abnormal,  Unusual,  or  Pathological  Conditions  of  the  Sweat. 
— Drugs. — Certain  drugs  (sudorifics)  favour  sweating,  e.g.,  pilocarpine, 
Calabar  bean,  strychnine,  picrotoxine,  muscarine,  nicotine,  camphor, 
ammonia.  Others  diminish  the  secretion,  e.g.,  atropine  and  morphine 
in  large  doses. 

Large  quantities  of  water,  by  raising  the  blood-pressure,  increase 
the  perspiration. 

Some  substances  introduced  into  the  body  reappear  in  the  sweat, 
e.g.,  benzoic,  tartaric,  and  succinic  acids  readily,  quinine  and  iodine 


CH.  XL.]  THE   SWEAT  611 

with  more  difficulty.  Compounds  of  arsenic  and  mercury  behave 
similarly. 

Diseases. — Cystine  has  been  found  in  some  cases  of  cystinuria; 
dextrose  in  diabetic  patients;  bile-pigment  in  those  with  jaundice 
(as  evidenced  by  the  staining  of  the  clothes);  indigo  in  a  peculiar 
condition  known  as  chromidrosis ;  blood  or  hsematin  deriva- 
tives in  red  sweat;  albumin  in  the  sweat  of  acute  rheumatism, 
which  is  often  very  acid ;  urates  and  calcium  oxalate  in  gout ;  lactic 
acid  in  puerperal  fever,  and  occasionally  in  rickets  and  scrofula. 

Kidney  Diseases. — The  relation  of  the  secretion  of  the  skin  to  that 
of  the  kidneys  is  a  very  close  one.  Thus  copious  secretions  of  urine, 
or  watery  evacuations  from  the  alimentary  canal,  coincide  with  dry- 
ness  of  the  skin ;  abundant  perspiration  and  scanty  urine  generally 
go  together.  In  the  condition  known  as  urcemia  (see  p.  588),  when 
the  kidneys  secrete  little  or  no  urine,  the  percentage  of  urea  rises 
in  the  sweat;  the  sputum  and  the  saliva  also  contain  urea  under 
those  circumstances.  The  clear  indication  for  the  physician  in 
such  cases  is  to  stimulate  the  skin  to  action  by  hot-air  baths  and 
pilocarpine,  and  the  alimentary  canal  by  means  of  purgatives.  In 
some  of  these  cases  the  skin  secretes  urea  so  abundantly  that  when 
the  sweat  dries  on  the  body,  the  patient  is  covered  with  a  coating  of 
urea  crystals. 

Varnishing  the  Skin. — By  covering  the  skin  of  such  an  animal  as 
a  rabbit  with  an  impermeable  varnish,  the  temperature  is  reduced,  a 
peculiar  train  of  symptoms  set  up,  and  ultimately  the  animal  dies. 
If,  however,  cooling  is  prevented  by  keeping  such  an  animal  in  warm 
cotton-wool,  it  lives  longer.  Varnishing  the  human  skin  does  not 
seem  to  be  dangerous.  Many  explanations  have  been  offered  to 
explain  the  peculiar  condition  observed  in  animals ;  retention  of  the 
sweat  would  hardly  do  it ;  the  blood  is  not  found  post-mortem  to 
contain  any  abnormal  substance,  nor  is  it  poisonous  when  transfused 
into  another  animal.  '  Cutaneous  respiration  is  so  slight  in  mammals 
that  stoppage  of  this  function  cannot  be  supposed  to  cause  death. 
The  animal,  in  fact,  dies  of  cold ;  the  normal  function  of  the  skin  in 
regulating  temperature  is  interfered  with,  and  it  is  animals  with 
delicate  skins  which  are  most  readily  affected. 


CHAPTEK    XLI 

GENERAL  METABOLISM 

THE  word  metabolism  has  been  often  employed  in  the  preceding 
chapters,  and,  as  there  explained,  it  is  used  to  express  the  sum  total 
of  the  chemical  exchanges  that  occur  in  living  tissues.  The  chemical 
changes  have  been  considered  separately  under  the  headings 
Alimentation,  Excretion,  Eespiration,  etc.  We  have  now  to  put  our 
knowledge  together,  and  consider  these  subjects  in  their  relation  to 
one  another. 

The  living  body  is  always  giving  off  by  the  lungs,  kidneys,  and 
skin  the  products  of  its  combustion,  and  is  thus  always  tending  to 
lose  weight.  This  loss  is  compensated  for  by  the  intake  of  food  and 
of  oxygen.  For  the  material  it  loses,  it  receives  in  exchange  fresh 
substances.  If,  as  in  a  normal  adult,  the  income  is  exactly  equal  to 
the  expenditure,  the  body-weight  remains  constant.  If,  as  in  a 
growing  child,  the  income  exceeds  the  expenditure,  the  body  gains 
weight;  and  if,  as  in  febrile  conditions,  or  during  starvation,  the 
expenditure  exceeds  the  income,  the  body  wastes. 

The  different  parts  of  the  body  have  very  different  compositions ; 
still,  speaking  of  the  body  as  a  whole,  Volkmann  and  Bischoff  state 
that  it  contains  64  per  cent,  of  water,  16  of  proteins,  14  of  fat,  5  of 
salt,  and  1  of  carbohydrates.  The  carbohydrates  are  thus  the  smallest 
constituent  of  the  body;  they  are  the  glycogen  of  the  liver  and 
muscles,  and  small  quantities  of  dextrose  in  various  parts. 

The  most  important,  because  the  most  abundant  of  the  tissues  of 
the  body,  is  the  muscular  tissue.  Muscle  forms  about  42  per  cent, 
of  the  body-weight,*  and  contains,  in  round  numbers,  75  per  cent,  of 
water  and  21  per  cent,  of  proteins;  thus  about  half  the  protein 
material  and  of  the  water  of  the  body  exist  in  its  muscles. 

The  body,  however,  does  not  remain  in  a  stable  condition ;  even 
while  nutrition  is  occurring,  destructive  changes  are  taking  place 
simultaneously;  each  cell  may  be  considered  to  be  in  a  state  of 
unstable  equilibrium,  undergoing  anabolic,  or  constructive  processes, 
on  the  one  hand,  and  destructive,  or  katabolic,  processes  on  the  other. 

*  The  following  is  in  round  numbers  the  percentage  proportion  of  the  different 
structural  elements  of  the  body :  skeleton,  16 ;  muscles,  42 ;  fat,  18  ;  viscera,  9 ; 
skin,  8;  brain,  2;  blood,  5. 
612 


CH.  XLL] 


GENERAL   METABOLISM 


613 


The  two  sides  of  metabolism  may  be  compared  by  means  of  a 
balance-sheet,  and  the  necessary  data  for  the  construction  of  such  a 
comparison  are: — 

(1)  The   weight   of   the  animal   before,  during,  and   after   the 
experiment. 

(2)  The  quantity  and  composition  of  its  food. 

(3)  The  amount  of  oxygen  absorbed  during  respiration. 

(4)  The  quantity  and  composition  of  urine,  faeces,  sweat,  and 
expired  air. 

(5)  The  amount  of  work  done,  and  the  amount  of  heat  developed. 
(The  subject  of  animal  heat  will  be  considered  in  the  next  two  chapters.) 

Water  is  determined  by  subtracting  the  amount  of  water  ingested 
as  food  from  the  quantity  lost  by  bowels,  urine,  lungs,  and  skin. 
The  difference  is  a  measure  of  the  katabolism  of  hydrogen. 

Nitrogen. — The  nitrogen  is  derived  from  proteins,  and  appears 
chiefly  in  the  urine.  Smaller  quantities  are  eliminated  in  sweat  and 
faeces.  From  the  amount  of  nitrogen  so  found,  the  amount  of 
proteins  which  have  undergone  katabolism  is  calculated.  Proteins 
contain,  roughly,  16  per  cent,  of  nitrogen ;  so  1  part  of  nitrogen  is 
equivalent  to  6 '3  parts  of  protein ;  or  1  gramme  of  nitrogen  to  30 
grammes  of  flesh. 

Fat  and  Carbohydrate. — Subtract  the  carbon  in  the  katabolised  pro- 
tein (protein  contains  54  per  cent,  of  carbon)  from  the  total  carbon 
eliminated  by  lungs,  skin,  bowels,  and  kidneys,  and  the  difference 
represents  fat  and  carbohydrate  which  have  undergone  katabolism. 

Balance  of  Income  and  Discharge  in  Health. 

In  Chapter  XXX.  tables  are  given  of  adequate  diets;  these 
will  in  our  balance-sheet  represent  the  source  of  income ;  the  other 
side  of  the  balance-sheet,  the  expenditure,  consists  of  the  excretions. 

We  may  select  as  our  example  a  typical  table  of  this  daily 
exchange  of  material  on  an  ordinary  diet  from  the  work  of  Petten- 
kofer  and  Voit.  In  the  first  experiment  the  man  did  no  work. 


Income. 

Expenditure. 

Food. 

Nitrogen. 

Carbon. 

Excretions. 

Nitrogen. 

Carbon. 

Water. 

Protein   .     137gr. 
Fat.        .     117  „ 
Carbohy- 
drate.    352  „ 
Water     .  2016  „ 

V19-5 

315-5 

Urine    . 
Faeces   . 
Expired 
air 

17'4 
2-1 

12-7 
14-5 

248-6 

1279 
83 

828 

19-5 

275-8 

2190 

614  GENERAL  METABOLISM  [CH.  XLL 

Here  the  body  was  in  nitrogenous  equilibrium,  and  it  eliminated 
more  water  than  it  took  in  by  174  grammes,  this  being  derived  from 
oxidation  of  hydrogen.  It  stored  39 '7  grammes  of  carbon,  which  is 
equivalent  to  52  grammes  of  fat. 

The  next  table  gives  the  results  of  an  experiment  on  the  same  man 
on  the  same  diet,  but  who  did  active  muscular  work  during  the  day  : — 

Expenditure.  Nitrogen.  Carbon.  Water. 

Urine 17'4  12'6  1194 

Faeces 2'1  14*5  94 

Expired  air  .....  309'2  1412 

19-5  336-3  2700 

It  is  important  to  notice  that  the  discharge  of  nitrogen  was 
unaltered,  while  that  of  both  carbon  and  hydrogen  was  increased. 
At  one  time  protein  was  considered  to  be  the  great  source  of 
muscular  energy ;  this  was  first  disproved  by  an  historical  experiment 
made  by  Tick  and  Wislicenus  on  themselves  in  their  ascent  of  the 
Faulhorn.  Nature  works  in  a  most  economical  way  in  reference  to 
protein  waste,  and  any  increase  in  nitrogenous  katabolism  which 
occurs  during  muscular  work  is  insignificant. 

The  balance-sheet  method  of  investigation,  though  one  of  great 
usefulness,  tells  us  very  little  of  the  details  which  lead  to  the  end 
results.  We  must  therefore  now  proceed  to  study  the  details,  and 
although  there  is  a  good  deal  of  guesswork,  and  even  ignorance  upon 
some  essential  points,  we  may  most  conveniently  consider  the 
question  under  the  three  headings  of  our  principal  food  materials, 
namely,  carbohydrates,  fats,  and  proteins. 

Metabolism  of  Carbohydrates. 

In  plants,  carbohydrates  are  synthesised  by  the  agency  of  chloro- 
phyll from  the  simple  materials  carbonic  acid  and  water,  which  form 
their  chief  foods.  The  first  substance  formed  is  probably  formic  alde- 
hyde, H.COH  (which  is  the  simplest  carbohydrate  known),  and 
this  by  condensation  is  converted  into  sugar,  and  finally,  into 
starch.  We  have  no  clear  evidence  that  a  synthesis  of  this  kind 
ever  takes  place  in  animals,  but  the  main  source  of  animal  carbo- 
hydrate is  vegetable  carbohydrate.  This  is  taken  in  the  food  and 
converted  into  glucose ;  the  glucose  is  taken  to  the  liver  and  stored 
as  glycogen,  and  in  the  liver  is  once  more  liberated  as  glucose,  and 
distributed  to  the  body  in  this  form.  The  change  from  glycogen  to 
sugar  is  the  work  of  an  enzyme.  Is  the  change  from  sugar  to 
glycogen  also  an  enzyme  action  ?  And  if  so,  is  another  enzyme 
responsible  for  it,  or  have  we  to  deal  with  a  case  of  reversible 
zymolysis  ?  This  is  one  of  many  unanswered  questions.  The  other 
important  animal  carbohydrate  is  lactose,  a  compound  of  dextrose 
and  galactose.  If  the  food  contains  galactose  as  well  as  dextrose,  the 


Cli.  XLL]  METABOLISM   OF   CARBOHYDRATES  615 

condensation  of  these  two  sugars  to  form  lactose  is  a  comparatively 
simple  problem ;  there  is  no  doubt  that  galactose  is  present  in  certain 
foods,  for  instance  it  is  contained  in  some  vegetables,  and  it  also 
comes  from  the  sugar  of  milk.  Lactose  in  the  mammary  gland  is, 
however,  not  the  only  place  where  galactose  is  necessary,  for  the 
galactosides  of  nervous  tissue  (see  p.  437)  also  contain  it.  But  it  is  not 
necessary  to  assume  that  all  the  galactose  necessary  for  the  formation 
of  milk  sugar  and  of  the  galactosides  comes  direct  from  the  galactose 
of  the  food.  Dextrose,  galactose,  and  laevulose  are  all  isomeric,  and 
the  intramolecular  rearrangements  that  would  be  necessary  to 
convert  one  into  another  member  of  this  group  do  not  seem  to  be 
beyond  the  power  of  the  tissue  cells,  and  there  is  a  good  deal  of 
evidence  that  such  transformations  actually  occur  in  the  body.  The 
other  carbohydrate  constituents  of  the  body  are  pentoses  found  in 
some  nucleo-proteins,  and  glucosamine  in  the  gluco-proteins,  but 
in  relation  to  these  our  knowledge  is  highly  speculative. 

It  is  further  known  that  the  hepatic  glycogen  may,  under  certain 
circumstances,  originate  from  proteins,  and  that  many  proteins  con- 
tain a  carbohydrate  radical ;  some,  such  as  mucin,  yield  a  considerable 
amount,  but  in  the  commoner  proteins,  the  amount  is  in  the  neigh- 
bourhood of  1  per  cent,  or  less.  The  mucins  do  not  participate  to  any 
great  degree  in  metabolism,  and  so  the  question  arises  whether  the 
small  amount  of  carbohydrates  in  the  ordinary  proteins  is  sufficient 
to  account  for  the  amount  of  glycogen  formed.  Arithmetic  shows  it 
will  not;  moreover,  a  protein  (such  as  casein)  which  contains  no 
carbohydrate  radical  at  all,  is  equally  efficacious  as  the  others  in 
yielding  sugar  when  administered  to  animals  suffering  from  glycosuria 
produced  by  phloridzin.  We  must  therefore  search  for  something 
in  the  protein  molecule,  as  the  source  of  the  carbohydrate,  and 
leucine,  having  like  sugar  6  atoms  of  carbon,  was  naturally  the  first 
substance  to  be  examined.  But  all  experiments  on  the  admini- 
stration of  leucine  led  to  negative  or  nearly  negative  results.  Another 
amino-acid,  alanine  (with  its  compounds  tyrosine,  phenyl-alanine,  and 
tryptophane),  was  found  to  be  the  much  more  probable  source  of 
the  carbohydrate.  The  relationship  of  alanine  to  the  carbohydrates 
is  a  near  one,  for  if  HO  is  substituted  in  its  molecule  for  NH2,  we 
get  lactic  acid,  and  it  was  found  that  the  administration  of  alanine 
to  rabbits  led  to  glycogen  formation  in  their  livers,  and  to  the 
passage  of  lactic  acid  into  their  urine.  Another  cleavage  product  of 
protein,  namely,  aspartic  acid,  may  act  in  a  similar  way,  and  this  also 
is  intelligible  on  chemical  lines,  for  if  aspartic  acid  loses  carbon 
dioxide,  it  is  converted  into  lactic  acid,  and  it  is  no  great  step  from 
this  to  sugar.  Similar  experiments  have  been  performed  with 
glycine  and  other  amino-acids,  but  the  results,  though  in  part  positive, 
are  by  no  means  go  clear,  nor  is  the  chemical  relationship  between 


616  GENERAL   METABOLISM  [CH.  XLI. 

them  and  carbohydrate  so  easy  to  understand.  Glycerin  is  another 
substance  the  conversion  of  which  into  carbohydrate  appears  to  be 
possible;  glyceric  aldehyde  is  isomeric  with  lactic  acid,  so  here 
again  we  have  a  feasible  explanation. 

Turning  now  to  the  other  side  of  the  picture,  what  information 
have  we  about  carbohydrate  katabolism  ?  The  final  products  of  com- 
bustion are  carbonic  acid  and  water,  but  what  are  the  intermediate 
steps  ?  Just  as  lactic  acid  has  been  assumed  to  be  sometimes  a 
stage  in  the  formation  of  sugar,  so  also  there  is  evidence  that 
it  is  a  stage  in  its  breakdown.  We  know  that  certain  micro- 
organisms possess  the  power  of  transforming  sugar  into  lactic  acid, 
and  even  still  further  into  butyric  acid  (see  formulae,  p.  411),  and 
Buchner  has  recently  asserted  that  lactic  acid  is  a  stage  in  the 
formation  of  alcohol  and  carbonic  acid  from  sugar  by  means  of  yeast. 
The  atoms  in  lactic  acid  (C3H603)  are  in  the  same  proportion  as  in 
sugar  (C6H1206),  but  of  course  they  are  very  differently  arranged, 
and  the  rearrangement  involved  in  the  conversion  of  the  one  into  the 
other,  or  vice  versd,  is  differently  explained  by  different  chemists. 
Lactic  acid  undoubtedly  occurs  in  the  body,  but  whether  it  all  comes 
from  sugar  is  extremely  doubtful.  The  principal  lactic  acid  found 
is  the  dextro-rotatory  variety  (sarco-lactic  acid),  whereas  that  formed 
in  fermentative  processes,  as  in  milk,  is  the  optically  inactive  variety. 
Now,  there  is  a  good  deal  of  evidence  that  sarco-lactic  acid  originates 
from  proteins;  for  instance,  in  the  birds  from  which  Minkowski 
removed  the  liver,  the  giving  of  protein  food  increased  the  lactic  acid 
(which  was  not  synthesised  in  the  absence  of  the  liver  into  uric  acid) 
of  their  urine,  and  we  have  further  seen  that  alanine  and  other 
protein  cleavage  products  are  possible  parent  substances  of  lactic 
acid.  Still,  if  we  admit  that  some  of  the  lactic  acid  is  of  carbohydrate 
origin,  and  the  admission  is  quite  justifiable,  we  must  remember  that 
such  a  breakdown  of  sugar  yields  no  heat;  the  calorific  value  of 
sugar  and  lactic  acid  being  equal.  The  formation  of  lactic  acid 
involves  no  transformation  of  energy ;  there  is  no  formation  of  animal 
heat,  or  of  its  equivalent  in  work,  and  so  the  change  is  merely 
preliminary  to  a  further  change  into  carbonic  acid  and  water,  in 
which  there  will  be  that  liberation  of  energy  which  it  is  the  main 
object  of  carbohydrate  breakdown  to  accomplish.  (G-lycolysis  in  the 
blood  and  tissues,  and  the  importance  of  glycuronic  acid  as  an  inter- 
mediate substance  in  carbohydrate  cleavage,  are  discussed  on  p.  540.) 

Metabolism  of  Pat. 

The  most  conspicuous  use  of  the  fat  in  the  body  is  to  act  as 
a  reserve  fund  of  fuel.  The  storage  of  100  calories  in  the  form  of 
fat  may  be  effected  in  the  space  of  about  12  c.c.  of  tissue,  weighing 


CH.  XL!.]  METABOLISM    OF   FAT  617 

about  11  grammes;  the  storage  of  the  same  amount  of  potential 
heat  as  glycogen  is  never  effected  in  less  than  ten  times  that  bulk 
of  liver  tissue  weighing  130  grammes,  and  rarely  in  less  than 
double  that  amount. 

Another  use  of  fat,  and  one  concerning  which  we  know  less,  is 
to  participate  in  the  actual  construction  of  protoplasm,  a  role  which 
is  not  exclusively,  though  it  is  mainly,  that  of  the  proteins.  In  this 
direction  it  is  probable  that  the  simple  fats  such  as  are  found  in 
adipose  tissue  are  less  concerned  than  the  more  complex  fats,  which 
contain  phosphorus  and  nitrogen  and  are  known  as  the  phosphatides. 
Many  years  ago  Hoppe-Seyler  pointed  out  that  these  lipoids  are 
as  universally  distributed  as  are  the  proteins  wherever  the 
phenomena  of  life  are  observable,  and  the  more  recent  work  of 
bio -chemists  has  fully  confirmed  the  view,  that  though  present 
usually  in  small  quantities,  they  are  nevertheless  indispensable. 

We  have  on  pp.  541,  542  seen  that  the  liver  is  important  from 
both  these  aspects.  It  not  only  prepares  the  fats  for  combustion 
into  their  final  products  (carbon  dioxide  and  water),  with  the 
simultaneous  liberation  of  heat,  but  it  is  also  of  use  in  synthesising 
the  more  complex  fatty  compounds,  the  importance  of  which  has 
just  been  alluded  to. 

Just  as  the  carbohydrate  of  the  food  is  the  usual  source  of  the 
carbohydrate  of  the  body,  so  the  fat  of  the  food  is  the  usual  source  of 
the  fat  of  the  body.  But,  again,  fat  may  arise  from  something  which 
is  not  fat  in  the  food. 

During  absorption,  the  fatty  acid  and  glycerin  components  of  the 
fat  undergo  a  temporary  separation,  but  they  soon  reunite,  and  the 
fat  which  is  not  needed  for  immediate  use,  passes  via  the  chyle  and 
blood  to  the  cells  of  adipose  tissue,  where  it  is  stored.  The  com- 
position of  the  body  fat  depends  to  some  extent  on  the  composition 
of  the  fat  in  the  food.  The  proportion  of  the  olein,  stearin,  and 
palmitin  in  the  fat  of  an  animal  can  be  varied  by  variations  in 
their  proportion  in  the  food,  and  if  unusual  glycerides  or  unusual 
fatty  acids  (such  as  linolein  from  linseed  oil,  erucic  acid  from  rape- 
seed  oil,  or  iodised  fats)  are  administered,  they  will  be  discoverable 
in  the  storage  fat  of  the  body. 

How  the  fat  which  is  transported  to  the  adipose  tissue  by  the 
blood  enters  the  cells  of  that  tissue  is  probably  to  be  explained  by 
the  existence  of  an  enzyme  in  the  cells ;  this  intracellular  lipase  acts 
as  the  pancreatic  enzyme  acts  in  the  intestine,  cleaving  fat  into  its 
soluble  constituents,  fatty  acid  and  glycerin ;  these  pass  through  the 
cell  membrane  and  are  once  more  re-synthesised  into  fat,  the  action 
of  lipase  being  a  reversible  one.  When  the  fat  leaves  the  cells  of 
adipose  tissue  for  utilisation,  that  is,  combustion  in  the  tissues,  lipase 
unties  the  knot  once  more,  and  so  fat  is  rendered  soluble  in  the 


618  GENERAL   METABOLISM  [CII.  XLI. 

blood  for  transportation.  There  is  no  loss  of  energy  in  this  process 
of  fat-hydrolysis,  any  more  than  there  is  in  the  formation  of  lactic 
acid  from  sugar ;  or,  to  use  the  technical  phrase,  the  reaction  is  an 
isothermic  one. 

Some  observers  have  failed  to  discover  lipase  in  the  cells  of  the 
tissues  which  contain  fat.  It  is  probable  that  here  as  in  the 
pancreas,  lipase  consists  of  two  parts,  an  inactive  component  and  an 
activator  (see  p.  520).  The  failure  to  discover  lipase  is  therefore 
probably  due  to  the  circumstance  that  only  the  inactive  portion  is 
present.  It  has  been  found  that  blood  or  blood-serum  has  no  power 
to  split  fats;  it,  however,  does  contain  the  activator  of  pancreatic 
lipase.  These  facts  justify  the  conclusion  that  the  co-enzyme  or 
activator  is  a  hormone  produced  in  the  pancreas,  and  carried  by  the 
blood  to  the  fat  depots  of  the  body,  enabling  the  tissue  lipase  to 
hydrolyse  the  fat  carried  to  them  by  the  blood-stream  after  digestion. 

The  fat  of  the  body  may  also  arise  from  carbohydrate  food. 
This  is  a  physiological  fact  which  was  first  firmly  established  by 
Lawes  and  Gilbert  in  their  classical  experiments  on  the  fattening 
of  pigs  sixty  years  ago.  The  transformation  is  a  monopoly  of 
the  living  body :  chemists  were  at  first  inclined  to  regard  the  fact  as 
fiction,  and  they  have  never  been  able  to  repeat  it  in  the  laboratory. 
How  the  long  carbon  chains  of  the  fat  are  linked  together  from  the 
shorter  carbohydrate  chains  of  sugar  is  at  present  a  riddle.  Micro- 
organisms can  accomplish  the  change  of  lactic  acid  into  such  fatty  acids 
as  acetic,  butyric,  and  caproic  ;  boiling  with  alkali  brings  about  a  similar 
reaction ;  and  the  same  sort  of  change  must  occur  in  the  body  with 
the  formation  of  higher  fatty  acids.  The  liver  appears  to  be  the 
place  where  the  change  occurs. 

May  fats  also  arise  from  proteins?  This  is  a  controversial 
question.  Yoit  and  Pettenkofer  said  yes,  because  they  were  able  to 
fatten  dogs  on  lean  meat,  but  as  the  amount  of  fat  left  in  the  meat, 
and  the  glycogen  also  present,  were  not  taken  into  account,  their 
proof  can  hardly  be  considered  satisfactory.  The  majority  of  physio- 
logists to-day  either  answer  the  question  in  the  negative,  or  regard  it 
as  unproven  one  way  or  the  other.  They  adopt  this  attitude  because 
the  main  proof  adduced  by  those  who  believed  in  the  transformation 
of  protein  into  fat  has  been  shown  to  be  fallacious.  It  was  stated 
that  in  certain  pathological  conditions,  for  instance  in  phosphorus 
poisoning,  a  fatty  degeneration  of  cells  of  certain  organs  takes  place, 
and  the  fat  which  appeared  was  believed  to  originate  from  the  pro- 
tein constituents  of  the  cell-protoplasm.  This  is  now  known  to  be 
incorrect ;  every  case  of  so-called  fatty  degeneration  has  been  shown 
to  be  either  due  to  an  infiltration  of  fat  transported  from  elsewhere,  or 
to  a  transformation  of  the  fat  previously  present  in  the  protoplasm, 
although  not  in  the  form  of  droplets,  and  probably  also  not  in  the 


CH.  XLL]  METABOLISM    OF   FAT  619 

form  of  the  usual  glycerides.  In  many  cases,  the  total  fat  present  in 
this  concealed  form  (possibly  in  combination  with  protein)  in  the 
cells  of  the  heart,  kidney,  and  liver  may  be  greater  than  when  with 
disease  it  takes  the  form  of  droplets. 

With  regard  to  the  origin  of  glycerin,  there  is  no  doubt  that  the 
cells  are  able  to  produce  it,  as  was  shown  by  Munk's  experiments 
on  chyle,  which  are  referred  to  on  p.  548.  There  is  no  necessity  to 
suppose  that  it  originates  from  protein,  for  if  glycerin  can  be  con- 
verted into  sugar,  there  is  good  ground  for  believing  that  the  converse 
also  takes  place. 

On  katabolism,  the  fats  yield  the  same  ultimate  products  as  the 
carbohydrates,  namely,  carbonic  acid  and  water.  A  great  deal  of 
the  oxygen  we  breathe  in  is  used  up  in  the  burning  of  fats,  and  the 
simultaneous  liberation  of  heat  and  work.  It  is  quite  certain  that 
sugar  is  an  important  source  of  muscular  energy,  but  the  fats  also 
play  the  same  role,  and  muscles  which  are  perpetually  at  work,  such 
as  the  heart  and  the  diaphragm,  are  particularly  rich  in  fats.  No 
actual  lessening  of  the  fat  has  yet  been  demonstrated  to  occur  in 
excised  muscles  subjected  to  stimulation,  but  we  have  other  and  more 
trustworthy  evidence  that  it  does  take  place.  During  muscular 
work,  the  output  of  carbonic  acid  is  increased,  but  the  respiratory 
quotient  is  almost  unaltered ;  if  sugar  alone  was  undergoing 
combustion,  this  quotient  would  rise.  Again,  if  the  carbohydrate 
stores  of  the  body  are  depleted  by  inanition,  or  by  giving  phloridzin 
to  an  animal,  muscular  work  has  but  little  influence  on  protein 
katabolism,  and  therefore  the  necessary  increased  combustion  must 
fall  on  the  fat.  But  how  the  long  carbon  chains  of  the  fatty  acids 
are  taken  to  pieces  and  burnt  up  is  very  largely  a  matter  of  guess- 
work ;  still  the  recent  work  of  Leathes  and  Hartley,  which  is  briefly 
summarised  on  p.  541,  has  given  us  some  insight  into  the  way  in 
which  the  liver  accomplishes  this  object.  Much  the  same  problem 
is  presented  when  we  consider  the  fate  of  the  proteins.  We  know 
fairly  accurately  how  the  protein  nitrogen  is  disposed  of,  but  the 
non-nitrogenous  residue  (which  is  chiefly  lower  fatty  acid,  and 
which  like  a  fat  is  used  for  combustion,  and  as  a  source  of  heat 
and  energy)  is  no  doubt  dealt  with  by  the  liver,  as  the  fats  them- 
selves are.  The  existence  of  this  non-nitrogenous  and  fat-like 
component  of  protein  should  make  physiologists  hesitate  before  they 
finally  deny  the  possible  conversion  of  the  food-protein  and  tissue- 
protein  into  fat. 

The  study  of  acidosis  or  acidaemia  referred  to  on  p.  542  is 
important,  because  it  sheds  light  on  the  phenomena  of  fat  katabolism  ; 
/3-hydroxybutyric  acid  and  acids  of  similar  molecular  size  are 
probably  normal  intermediate  products  in  the  process;  a  healthy 
man  on  a  properly  mixed  diet  is  able  to  oxidise  /3-hydroxybutyric 


620  GENERAL   METABOLISM  [CH.  XLI. 

acid  in  his  liver  into  aceto-acetic  acid,  and  then  finally  burn  that 
acid  into  carbonic  acid  and  water.  The  diabetic  patient  breaks 
down  at  this  very  point;  he  is  able  to  form  a  certain  amount  of 
aceto-acetic  acid,  but  this  passes  unchanged  into  his  urine,  or  if  any 
is  changed  at  all,  it  is  not  into  carbonic  acid  and  water,  but  into 
acetone  instead. 

Our  next  question  is  whether  during  life  fat  may  be  converted 
into  carbohydrate  ?  In  plants,  the  utilisation  of  fats  by  the  embryo 
during  germination  has  been  studied.  When  growth  begins  enzymes 
are  formed  which  hydrolyse  fats,  and  v.  Fiirth  found  in  his  work 
on  the  oil  in  the  seeds  of  the  sunflower  and  castor-oil  plant  that 
the  changes  which  occur  consist  in  an  increase  in  the  saponification 
value  and  a  lowering  in  the  iodine  and  acetyl  values.  The  increase 
in  the  saponification  value  indicates  a  fall  in  the  molecular  weight 
of  the  fatty  acids,  that  is  to  say,  the  formation  of  lower  fatty 
acids  from  higher  ones  has  occurred ;  the  lowering  of  the  iodine  and 
acetyl  values  indicates  that  it  is  the  unsaturated  linkages  and  the 
hydroxylated  carbon  atoms  that  have  been  the  weak  places  where 
the  cleavage  has  occurred.  But  beyond  these  observations  there  is 
nothing  known  of  the  metabolism  of  fats  in  plants ;  certainly  any 
evidence  that  they  are  transformed  into  carbohydrates  is  lacking. 

The  evidence  that  the  transformation  of  fats  into  carbohydrates 
can  occur  in  animals  is  also  indirect  or  unsatisfactory.  Pflliger 
argued  that  in  glycosuria  following  extirpation  of  the  pancreas,  or 
phloridzin  administration  in  dogs,  large  quantities  of  fat  are  con- 
verted into  sugar.  This  was  an  assumption  based  upon  the  idea 
that  none  of  the  sugar  could  have  been  formed  from  protein.  This 
view  does  not  accord  with  the  observations  and  opinions  of  others 
who  have  worked  at  the  subject,  and  for  many  years  Pfliiger  fought 
in  his  usual  strenuous  manner  for  his  own  view  that  protein  can 
never  be  a  source  of  sugar.  However,  facts  were  too  strong 
for  him,  and  in  almost  the  last  paper  he  wrote  before  he  died  he 
withdrew  it. 

We  have  already  seen  the  chemical  difficulties  of  explaining  how 
sugar  can  be  converted  into  fat,  but  it  is  a  fact  nevertheless.  The 
difficulty  of  explaining  the  converse  change  is  equally  great;  still 
in  spite  of  this  difficulty  and  in  spite  of  the  unsatisfactory  nature 
of  any  proofs  that  this  actually  occurs  during  life,  it  cannot  be 
maintained  that  the  formation  of  sugar  from  fatty  acids  is  impossible ; 
for  we  have  already  seen  that  the  formation  of  sugar  from  certain 
amino-acids  such  as  alanine,  which  are  of  protein  origin,  has  been 
proved  to  occur.  Amino-acids  deprived  of  their  amino-group  are  fatty 
acids ;  alanine,  for  instance,  minus  its  amino-group,  is  propionic  acid. 
The  ultimate  fate  of  lower  fatty  acids  derived  from  fats  can  hardly 
be  different  from  that  of  those  which  are  derived  from  proteins. 


CH.  XLI.]  METABOLISM   OF   PROTEIN  621 

Metabolism  of  Protein. 

In  our  discussion  of  the  origin  of  urea  in  the  urine,  we  have 
mentioned  some  of  the  main  facts  in  relation  to  the  metabolism 
of  proteins,  and  it  would  be  well  if  the  student  again  reads  these 
pages  (pp.  586  to  588)  before  studying  the  paragraphs  which  now 
follow;  for  the  laws  which  govern  the  composition  of  urine  are 
the  effect  of  more  fundamental  laws  governing  protein  katabolism. 

Liebig  was  the  first  to  divide  foods  into  flesh-forming  and  heat- 
forming,  that  is,  into  those  which  repair  the  tissue  waste,  and  those 
which  are  not  so  intimately  assimilated  into  the  protoplasm,  but  are 
utilised  as  sources  of  energy.  The  latter  function  is  the  one  per- 
formed by  the  fats  and  carbohydrates,  and  the  former  is  more 
particularly  the  duty  of  the  proteins.  This  idea  is  reflected  in  the 
popular  use  of  the  term  nutritious ;  it  is  used  almost  synonymously 
with  nitrogenous,  and  the  notion  that  the  non-nitrogenous  foods, 
although  they  form  the  greater  part  of  our  daily  diet,  are  not 
nutritious  and  next  door  to  useless,  is  a  most  mischievous  one, 
though  it  is  carefully  fostered  by  the  advertisers  of  patent  foods. 
Both  kinds  of  food  are  equally  necessary,  and  equally  though 
differently  nutritious. 

It  is  now  known  that  the  proteins  are  not  only  flesh-formers, 
but  also  that  they  play  the  other  role  in  nutrition  and  act  as  a  source 
of  energy.  The  complete  breakdown  into  amino-acids  which  occurs 
in  the  gastro-intestinal  tract,  has  in  fact  a  double  signification.  It 
enables  the  cells  of  the  body  to  construct  from  the  cleavage  products 
the  proteins  peculiar  to  themselves,  and  it  further  enables  the  body 
to  easily  rid  itself  of  the  nitrogenous  portions  of  the  food-proteins 
which  are  not  wanted  for  the  repair  of  tissue  waste.  This  portion  is 
never  really  assimilated  in  the  sense  that  it  is  built  into  protoplasm, 
but  it  is  taken  in  by  the  liver  cells,  which  deamidise  it  and  convert 
the  nitrogenous  portion  into  urea.  The  non -nitrogenous  moiety  is 
then  utilisable  for  energy  and  heat  production. 

In  starvation,  the  income  of  the  body  is  limited  to  oxygen,  but 
if  water  is  given  also,  an  animal  will  generally  live  a  little  over  four 
weeks.  During  this  time  the  excretion  of  nitrogenous  and  carbona- 
ceous waste  continues  and  the  body  loses  weight  day  by  day.  The 
excretion  of  carbon  dioxide  continuously  falls  until  death  supervenes. 
The  nitrogen  of  the  urine  falls  also  within  the  first  few  days,  and 
then  remains  at  a  low  but  constant  level  to  the  end  of  the  fourth 
week.  Then  for  the  few  days  preceding  death,  its  amount  again 
increases.  By  this  date  nearly  every  trace  of  the  fat  of  the  body 
has  disappeared,  and  so  the  cells  fall  back  on  their  more  precious 
protein  material  and  consume  it  in  greater  quantity  than  before. 
The  nitrogen  elimination  during  the  weeks  when  it  remains  constant 


622  GENERAL   METABOLISM  [CH.  XLI. 

must  be  derived  from  the  proteins  of  the  body,  for  there  is  none 
coming  in,  in  the  way  of  food.  It  might  be  thought  if  at  this  time 
an  amount  of  protein  food  containing  the  same  quantity  of  nitrogen 
as  was  being  lost  by  the  body,  was  administered,  that  the  loss  of 
nitrogen  from  the  body  would  be  checked,  and  that  the  tissues  would 
seize  the  opportunity  of  repairing  their  waste.  But  this  is  not  the 
case ;  what  happens  is  that  the  amount  of  nitrogen  lost  in  the  day  is 
almost  doubled ;  and  this  is  an  undoubted  proof  that  nearly  all  the 
protein  in  the  food  is  disintegrated  and  its  nitrogen  discharged 
within  the  twenty-four  hours.  In  order  to  get  nitrogenous  equili- 
brium, it  is  necessary  to  give  in  the  day  two  and  a  half  times  as 
much  protein  as  is  lost  during  starvation  in  that  period  of  time.* 
This  was  one  of  the  earliest  proofs  adduced  that  all  the  food  protein 
is  not  used  in  tissue  repair,  and  it  led  Voit  to  formulate  his  cele- 
brated theory  of  the  distinction  between  "  tissue  protein  "  and  what 
he  termed  "circulating  protein."  The  latter  expression  was  coined 
because  Voit  believed  that  the  katabolism  of  this  variety  of  protein 
occurred  in  the  blood,  or  at  any  rate  in  the  tissue  juices.  In  fact, 
he  considered  that  katabolism  occurred  only  in  the  "circulating 
protein,"  the  small  amount  of  "living  protein"  which  dies  being 
dissolved  and  so  added  to  the  "  circulating  protein  "  before  katabolism 
occurs.  Voit's  great  opponent  was  Pniiger,  and  for  many  years 
Pflliger's  theory  replaced  Voit's ;  this  theory  states  that  all  protein 
must  first  become  assimilated ;  that  is,  must  be  built  into  and  become 
part  and  parcel  of  living  protoplasm  before  it  undergoes  katabolism. 
Pfliiger  did  good  service  in  emphasising  the  importance  of  the  cells 
in  metabolic  processes,  and  we  certainly  do  not  now  believe  that 
respiration  or  any  other  metabolic  process  has  its  seat  in  the  circulat- 
ing fluids.  But  at  the  same  time  Voit's  theory  possesses  the  correct 
underlying  idea  which  forms  the  basis  of  our  present  doctrine  of 
metabolism.  In  every  living  tissue  there  exists  a  framework  of 
what  we  may  call  more  distinctly  living  substance,  the  metabolism 
of  which  is  constant  and  does  not  give  rise  to  massive  discharges  of 
energy;  in  the  interstices  of  this  are  various  kinds  of  material 
related  in  different  degrees  to  this  framework ;  these  materials  are 
less  eminently  living,  and  the  chief  part  of  the  energy  set  free  comes 
directly  from  the  metabolism  of  some  or  other  of  this  material. 
Both  the  framework  and  the  intercalated  material  undergo  met- 
abolism, and  have  in  different  degrees  their  anabolic  and  katabolic 

*  It  has  recently  been  stated  by  Michaud  that  this  amount  may  be  greatly 
reduced  by  feeding  the  animal  on  proteins  which  are  as  near  as  possible  in  com- 
position to  the  tissue  proteins  of  the  animal,  for  instance,  by  feeding  a  dog  on  dog's 
flesh.  Knowing,  however,  as  we  do  now  that  during  digestion  protein  material 
undergoes  almost  complete  cleavage,  it  is  difficult  to  accept  such  a  view,  and  many 
observers  have  not  confirmed  the  experiments,  or  at  least  have  shown  that  the 
advantage  is  far  less  than  Michaud  found. 


CH.  XLI.]  METABOLISM   OF   PROTEIN  623 

changes;  both  are  concerned  in  the  life  of  the  organism;  but  one 
more  directly  than  the  other.  When  we  now  speak  of  endogenous 
protein  metabolism  we  refer  to  that  in  the  material  highly  endowed 
with  life;  when  we  apply  the  term  exogenous  protein  metabolism  to 
the  changes  by  which  the  liver  brings  about  the  conversion  of  amino- 
acids  from  the  food  into  urea,  we  refer  to  its  action  on  intercalated 
material,  and  no  longer  use  the  phrase  "  circulating  protein." 

We  have  already  discovered  in  our  study  of  the  urine,  that 
exogenous  protein  katabolism  is  mainly  represented  in  the  urine  by 
urea  and  inorganic  sulphates;  while  the  final  katabolites  of  endo- 
genous metabolism  are  substances  like  creatinine  and  "  neutral 
sulphur";  but  there  is  no  doubt  that  some  urea  is  formed  also:  this 
is  seen,  for  instance,  during  starvation. 

Let  us  consider  a  man  taking  the  customary  Voit  dietary  of 
16  or  17  grammes  of  nitrogen  in  his  daily  food;  probably  only  a 
quarter  or  even  less  of  this  is  destined  for  endogenous  use,  and  the 
protein  sufficient  to  maintain  this  is  indispensable.  Would  it  be 
possible  to  dispense  entirely  with  the  amount  which  is  exogenously 
metabolised,  and  reduce  our  protein  intake  to  the  low  level  of,  say, 
4  grammes  of  nitrogen  per  diem.  The  old  observations  on  starving 
animals  we  have  just  referred  to  shows  that  this  would  not  be 
possible;  the  minimum  is  not  the  optimum;  and  even  Chittenden 
(see  p.  480)  does  not  recommend  a  reduction  lower  than  7  or  8  daily 
grammes  of  nitrogen.  If  an  animal  cell  is  presented  only  with 
protein  food,  it  takes  and  uses  it  eagerly,  even  although  it  may  not 
ultimately  build  much  of  it  into  protoplasm.  If  substances  such  as 
fat,  carbohydrate,  or  the  incomplete  protein  we  call  gelatin,  is'  pre- 
sented to  it  also,  the  amount  of  protein  necessary  is  reduced,  and 
so  we  speak  of  such  foods  as  being  "protein -sparing." 

The  important  character  of  Chittenden's  work  has  given  the 
faddists  on  matters  of  diet  an  important  opportunity  of  being 
listened  to.  There  is,  for  instance,  a  group  of  these  to  whom 
the  very  necessary  act  of  chewing  has  assumed  almost  the  nature 
of  a  religious  ceremony,  and  they  have  sought  to  convince  mankind 
of  its  superlative  importance.  These,  however,  need  not  concern 
us,  but  there  are  some  even  in  the  scientific  world  who  seem  almost 
to  believe  that  the  law  of  conservation  of  energy  does  not  apply  to 
the  chemical  changes  in  a  living  animal.  They  cite  instances  of 
people  who  do  a  large  amount  of  work,  and  do  it  upon  what  most 
would  regard  as  an  insufficient  diet,  without  detriment  or  loss  of 
body-weight.  If  a  man  only  receives  food  in  the  day  of  the  energy 
value  say  of  1500  large  calories,  and  the  heat  he  produces  and  the 
work  he  does  are  equivalent  to  2000 ;  then  the  additional  500 
must  have  come  from  his  internal  resources,  and  he  must  have  used 
up  some  of  the  material  formerly  stored  in  his  body.  This  is  as 


624  GENERAL   METABOLISM  [CH.  XLT. 

certain  as  is  the  fact  that  one  and  one  make  two.  It  is  quite  conceiv- 
able that  his  body  may  not  have  lost  weight,  but  nevertheless  fat 
may  have  disappeared,  and  been  replaced  by  an  equivalent  weight 
of  water,  and  excess  of  carbohydrate  food  which  usually  is  a  char- 
acter of  the  diets  of  such  people  is  just  the  sort  of  diet  likely  to 
cause  retention  of  water  in  the  body. 

We  have  in  our  mention  of  the  Chittenden  diet  alluded  to 
several  circumstances  that  should  make  us  pause  before  we  accept 
his  conclusions  to  the  full.  Many  people  eat  too  much ;  would  it  be 
advisable  for  us  all  to  eat  too  little,  and  is  Chittenden's  diet  too 
scanty  ? 

No  doubt  the  over-eaters  would  benefit  by  eating  too  little  for  a 
time.  They  would  give  their  overtaxed  digestive  and  secretory 
organs  a  necessary  rest,  and  have  time  to  consume  some  of  their 
accumulated  stores  of  material.  It  is  quite  possible  that  the  benefit 
noticed  in  some  of  the  subjects  of  Chittenden's  experiments  might 
have  been  due  to  such  a  circumstance  as  this,  or  to  the  regular  life 
they  were  compelled  to  live,  quite  apart  from  diet  altogether.  But 
to  eat  too  little  as  an  ordinary  and  permanent  thing  is  quite  another 
matter ;  and  it  is  interesting  to  be  able  to  record  that  most  of  the 
subjects  of  Chittenden's  experiments  have  now  returned  to  their 
previous  dietetic  habits. 

So  far  as  it  is  possible  to  read  history  correctly,  man  has  always, 
where  he  can,  taken  instinctively  more  protein  than  Chittenden 
would  allow  him,  and  with  few  exceptions,  the  meat-eating  nations 
are  those  which  have  risen  to  the  front. 

So  far  as  it  is  possible  to  draw  correct  deductions  on  questions  of 
diet  from  animals  to  man,  a  restricted  diet  over  a  long  period  has 
proved  detrimental.  Moreover,  a  careful  study  of  Chittenden's  own 
analytical  figures,  such  as  Benedict  has  made,  shows  there  was  in 
some  cases  distinct  impairment  of  health. 

But  still  the  question  remains,  why  an  apparently  large  excess  of 
nitrogen  which  the  body  casts  out  within  a  few  hours  should  be 
advisable  ?  The  answer  to  this  appears  to  be,  that  though  most  of 
the  cleavage  products  are  dealt  with  in  this  way,  there  are  some 
which  are  especially  precious  for  tissue  reconstruction,  and  it  is  for 
these  that  we  put  up  with  the  excess  of  waste.  The  large  size 
and  activity  of  the  normal  liver  seem  to  be  for  the  express  purpose 
of  dealing  with  this  waste  rapidly. 

Nature  does  not  work  in  minimums :  Leathes  puts  it  very  well 
when  he  says  it  is  not  considered  unphysiological  to  take  more  food 
than  ^will  yield  the  minimum  of  faecal  refuse ;  and  he  also  points  out 
that  in  the  infant,  even  allowing  for  its  growth,  the  normal  amount 
of  milk  provided  for  it  by  nature  is  ten  times  greater  than  would 
appear  to  be  the  necessary  minimum ;  and  this  is  probably  a  safer 


CH.  XLI.]  METABOLISM   OF   PROTEIN  625 

argument  than  the  one  so  often  used  when  the  instinctive  habits  of 
past  centuries  of  adults  are  appealed  to. 

We  may  also  draw  a  useful  lesson  from  disease.  In  the  modern 
treatment  of  consumption,  the  open-air  cure  is  combined  with  a  steady 
process  of  generous  feeding ;  in  certain  cases  of  nervous  breakdown, 
an  important  part  of  the  "  rest  cure "  is  the  providing  of  abundant 
and  appetising  meals.  One  can  hardly  doubt  that  much  of  the 
benefit  noticeable  in  both  classes  is  due  to  the  "reserve  energy" 
provided,  enabling  the  body  more  fully  to  grapple  with  the  malady. 
"Reserve  energy"  may  be  objected  to  as  a  vague  phrase  which, 
though  comforting  to  those  who  use  it,  is  nevertheless  very  difficult 
to  explain.  There  is  a  good  deal  of  reason  in  such  an  objection,  for 
"  reserve  force  "  is  difficult  to  define  clearly.  We  have,  for  instance, 
no  knowledge  of  any  storage  places  for  protein,  in  the  same  way  in 
which  the  liver  and  adipose  tissue  act  as  storehouses  for  carbohydrate 
and  fat  respectively.  But  it  is  an  undoubted  factor  all  the  same ; 
many  people  have  more  of  it  than  others ;  and  this  "  stamina,"  as  it 
is  sometimes  called,  is  a  lucky  possession  for  those  who  have  it. 
Research  on  immunity  has,  however,  shown  us  that  this  is  in  part  due 
to  the  condition  of  our  leucocytes,  and  the  opsonic  power  of  the 
blood-plasma  (see  p.  476).  It  may  be  that  it  is  in  this  direction 
among  others,  that  the  abundance  of  protein  food  may  assist  us  in 
repelling  disease.  Each  leucocyte  may  not  require  much  in  the 
way  of  repair  every  day,  but  it  is  more  likely  to  get  this  "  stitch  in 
time"  if  there  is  an  abundant  supply  of  repairing  material 
available. 

Rubner  has  called  attention  to  what  he  terms  the  specific  dynamic 
action  of  food-stuffs.  Weight  for  weight,  fat  yields  more  heat  when 
burnt  than  protein  does,  and  outside  the  body  it  is  more  easily 
combustible  than  either  protein  or  carbohydrate.  Inside  the  body 
it  is  just  the  reverse;  proteins  are  the  most  readily  burnt  of  any 
food  material,  and  fats  the  least.  In  other  words,  proteins  (and  the 
same  is  true  for  arnino-acids)  have  a  specific  value  in  stimulating 
metabolism,  and  so  leading  to  an  increase  of  oxidation  in  the 
body.  Some  of  the  subjects  of  Chittenden's  experiments  suffered 
intensely  from  the  cold  in  the  winter,  and  this  use  of  protein  must 
not  be  lost  sight  of  in  settling  the  right  amount  which  we  should 
take  in  our  daily  food. 

Some  attempt  has  been  made  to  determine  which  of  the  protein 
cleavage  products,  or  Bausteine,  to  use  the  German  term,  are  specially 
valuable  in  the  body,  either  for  the  synthesis  of  tissue  protein,  or,  as 
Hopkins  has  suggested,  for  the  formation  of  the  special  hormones  or 
chemical  messengers  of  the  body,  such  as  adrenaline. 

Recent  research  has  established  the  fact  that  one  of  the  important 
building  stones  for  these  purposes  is  phenyl-alanine,  and  its  near 

2  R 


626  GENERAL   METABOLISM  [CH.  XLT. 

relative  tyrosine  is  another;  for  when  they  are  injected  into  the 
blood-stream  they  do  not  reappear  as  urea  in  the  urine.  We  also 
know  that  proteins  which  yield  no  tyrosine,  such  as  gelatin,  are  of 
inferior  value  as  food.  Gelatin  is  also  destitute  of  the  tryptophane 
radical,  arid  tryptophane  is  specially  useful  too.  Zein,  the  protein 
of  maize,  lacks  tryptophane,  and  if  tryptophane  is  added  to  a  zein 
diet,  animals  fed  on  the  mixture  thrive  better  than  those  whose  sole 
nitrogenous  food  is  zein.  Histidine  and  pyrrolidine  have  been  sug- 
gested as  being  in  the  same  category,  but  here  we  must  await  further 
information. 


Growth  and  Maintenance.      Synthesis  in  the  Body. 

The  different  members  of  the  protein  family  have  thus  unequal 
powers  in  repairing  the  body  waste.  Still  more  important  is  their 
difference  in  promoting  growth  in  young  animals.  Eecent  work  by 
Osborne,  Mendel,  and  others  has  shown  that  it  is  possible  to  keep 
animals  alive  and  in  health  when  they  receive  their  nitrogen  in  the 
form  of  one  protein  only,  mixed  of  course  with  the  proper  supply  of 
non-nitrogenous  food.  But  if  these  animals  are  growing,  the  choice 
of  the  protein  given  is  a  matter  of  great  importance.  Eepair  pro- 
cesses in  the  adult  are  of  a  different  character  from  those  of  growth 
in  the  young  animal;  in  the  adult  cell,  katabolism  and  repair  do  not 
involve  the  destruction  and  resynthesis  of  entire  protein-molecules, 
such  as  obviously  must  be  the  case  when  growth  is  taking  place. 
This  work  has  also  brought  to  light  the  fact  that,  in  the  animal  body, 
there  is  a  power  of  synthesising  comparatively  simple  food  material 
into  more  complex  substances  far  in  excess  of  what  was  previously 
considered  to  be  the  case.  Thus  lipoids  can  be  built  from  inorganic 
phosphorus  compounds,  and  proteins  constructed  from  amino-acids. 
Some  even  have  asserted  that  ammonium  salts  given  by  the  mouth 
can  be  utilised  for  protein  construction,  but  this  has  not  yet  been 
conclusively  proved.  The  body  also  possesses  the  power  of  building 
up  amino-acids  which  are  absent  from  the  food,  and  of  converting  one 
ammo-acid  into  others.  This  ability  is  most  marked  in  the  adult 
animal ;  it  is  in  the  young  animal  that  the  actual  administration  in 
the  food  of  the  necessary  building  stones  is  indispensable. 

Let  us  take  one  or  two  instances  which  illustrate  this.  Eats  were 
fed  for  long  periods  on  food  mixtures  which  contained  only  a  single 
protein.  When  gliadin,  edestin,  or  caseinogen,  proteins  of  very 
different  composition  were  administered,  the  animals  thrived  and 
showed  neither  loss  of  weight  nor  any  other  metabolic  disorder. 
Glycine  is  absent  from  caseinogen,  lysine  and  glycine  from  gliadin, 
phosphorus  from  gliadin  and  edestin,  and  purines  were  absent  from 


CH.  XLL]  VITAMINES  627 

all  three.  The  synthetic  activities  of  the  animal  body,  or  the  possi- 
bility of  the  transmutation  of  one  amino-acid  into  others  are  thus 
clearly  brought  to  mind. 

My  next  example  may  be  taken  from  an  animal  higher  in  the 
scale.  A  food-mixture  in  which  gliadin  was  the  only  source  of 
nitrogen  was  given  to  a  puppy  in  place  of  its  mother's  milk ;  this 
produced  typical  failure  in  growth.  Nevertheless  the  mother  dog 
thrived  on  the  same  diet  and  actually  produced  young,  and  secreted 
milk  in  sufficient  quantity  and  quality  to  induce  normal  growth  in 
her  offspring.  No  stronger  proof  could  be  adduced  of  a  power  in  the 
adult  body  to  synthesise  "Bausteine"  which  are  absent  from  the 
food.  The  liver  cells  have  been  usually  credited  with  the  main  share 
in  such  marvellous  synthetic  power ;  but  there  is  a  reaction  in  the 
minds  of  physiologists  just  now  against  this  tendency  to  pile  up 
hepatic  duties.  Several  pieces  of  work  show  that,  although  the  liver 
doubtless  does  its  due  share  of  the  work,  other  tissues  and  organs 
also  participate  in  it. 

The  only  other  example  I  select  from  the  large  mass  of  material 
at  hand  illustrates  the  importance  of  those  unknown  but  indispens- 
able constituents  of  a  diet  which  are  referred  to  in  our  chapter  on 
Foods  (p.  491).  An  animal,  or  at  any  rate  a  growing  animal,  cannot 
live  on  protein  alone,  even  if  it  is  mixed  with  appropriate  mineral 
salts,  and  with  a  proper  supply  of  fat  and  carbohydrate  to  supply 
the  necessary  energy ;  these  other  organic  compounds  of  uncertain 
nature  are  absolutely  indispensable.  F.  G.  Hopkins  was  one  of  the 
earliest  to  recognise  the  importance  of  what,  for  want  of  a  better  name, 
we  may  term  these  accessory  factors  in  a  dietary,  and  the  effect  of 
quite  small  quantities  of  such  substances  is  admirably  illustrated  in 
his  most  recently  published  work.  Groups  of  young  rats  were  fed 
on  a  diet  of  caseinogen,  fats,  carbohydrate,  and  salts,  and  compared 
with  other  rats  on  the  same  diet,  plus  a  minute  ration  of  fresh  milk. 
The  former  soon  ceased  to  grow;  the  latter  grew  normally.  The 
consumption  of  food  was  practically  the  same  in  all  the  animals,  but 
the  milk  addendum  reduced  the  food  necessary  for  a  given  increment 
in  weight  to  one-half  or  less.  Moreover,  cessation  of  growth  occurred 
before  there  was  any  loss  of  appetite  to  account  for  it.  What  the 
actual  substances  are  in  the  milk  which  thus  markedly,  although  in 
a  secondary  way,  affect  growth  is  not  yet  known.  We  can  therefore 
only  surmise  that  the  unknown  material  (provisionally  termed 
vitamine)  may  contain  some  particular  "Bausteine"  which  the 
animal  body  is  not  able  to  build  up  for  itself ;  or  it  may  be  that  the 
effect  is  due  to  a  stimulating  effect  upon  the  cell-protoplasm  which 
leads  to  the  development  of  the  necessary  synthetic  power.  Funk 
has  suggested  that  the  "  vitamines  "  are  derivatives  of  pyrimidine. 


628 


GENERAL   METABOLISM 


[CH.  XLI. 


Inanition  or  Starvation. 

During  starvation  the  body  gradually  loses  weight ;  the  tempera- 
ture, after  a  preliminary  rise,  sinks;  the  functions  get  weaker  by 
degrees,  and  ultimately  death  ensues  when  the  body  has  lost  about 
50  per  cent,  of  its  original  weight.  Death  may  be  delayed  somewhat 
by  artificial  warmth,  so  that  the  strain  on  the  internal  production  of 
heat  is  not  so  great.  If  water  is  given,  life  may  continue  for  rather 
more  than  a  month.  The  age  of  the  animal  influences  the  time  at 
which  death  occurs.  This  statement  was  originally  made  by 
Hippocrates,  and  has  been  borne  out  by  the  experiments  of  Martigny 
and  Chossat.  Young  animals  lose  weight  more  quickly,  and  die 
after  a  smaller  loss  of  weight  than  old  ones. 

The  following  table  from  Ranke's  experiment  on  himself  repre- 
sents by  the  balance-sheet  method  the  exchange  for  a  period  of 
twenty-four  hours,  the  same  time  having  elapsed  since  the  last 
meal. 


Income,  due  to  disintegration  of  Tissues. 

Expenditure,  obtained  by  analysing  the 
Excretions. 

Nitrogen. 

Carbon.     ' 

Nitrogen. 

Carbon. 

Protein  .        50  gr. 
Fat         .      200  „ 

7-8 

o-o 

26-5 
157'5 

Urine    . 
Respiration  (CO2) 

7-8 

o-o 

3-4 
180-6 

7-8 

184-0 

7-8 

184-0 

The  excretion  of  nitrogen  falls  quickly  at  the  commencement  of 
starvation,  and  even  on  the  first  day  the  above  table  shows  us  it  has 
sunk  to  half  the  normal.  This  lessening  goes  on  for  a  few  days, 
after  which  it  remains  constant ;  about  the  end  of  the  fourth  week  it 
rises  again  when  the  fat  of  the  animal  has  been  used  up,  and  the 
body  makes  an  increased  call  on  the  protein  constituents  of  its 
protoplasm.  With  the  onset  of  symptoms  of  approaching  death, 
which  is  sometimes  accompanied  by  convulsions,  the  excretion  of 
nitrogen  rapidly  falls  again.  The  sulphates  and  phosphates  of  the 
urine  show  much  the  same  series  of  changes.  The  discharge  of 
carbonic  acid  and  the  intake  of  oxygen  fall  continuously  over  the 
whole  period. 

It  is  important  to  note,  that  wasting  does  not  occur  to  an  equal 
extent  in  all  the  tissues  and  organs.  Those  which  are  most  essential 
to  life  are  fed  at  the  expense  of  the  others ;  thus  the  heart  loses  little 
or  none,  and  the  central  nervous  system  loses  at  most  3  per  cent,  of  its 


CH.  XLI.] 


INANITION 


629 


weight.  The  fat  nearly  all  disappears,  at  least  97  per  cent,  of  it 
being  used  up ;  muscles  lose  30  per  cent,  of  their  original  weight, 
and  most  of  the  other  organs  suffer  also  but  in  varying  degrees. 
Taking  the  total  loss  as  100,  Voit  gives  the  loss  due  to  that  of 
individual  organs  as  follows : — 


Bone . 

Muscle 

Liver 

Kidneys 

Spleen 


5*4  I  Pancreas  . 

42-2  Lungs 

4:8  I  Heart 

0-6  !  Testes       . 

0'6  Intestines 


O'l 
0-3 
O'O 
O'l 
2-0 


Brain  and  cord 
Skin  and  hair 
Fat    . 
Blood 
Other  parts 


O'l 

8-8 

26-2 

37 

5-0 


CHAPTEK  XLII 

THE  CONSERVATION   OF  ENERGY 

THE  nutrition  of  the  body  has  been  considered  in  the  preceding  pages 
from  the  standpoint  of  a  detailed  examination  of  the  fate  of  the 
various  foodstuffs  which  enter  the  body  from  the  alimentary  canal. 
Furthermore,  by  a  consideration  of  the  substances  which  the  body 
excretes,  an  attempt  has  been  made  to  arrive  at  some  understanding 
of  the  processes  of  metabolic  activity. 

The  knowledge  thus  obtained  is  of  more  than  theoretical  interest. 
It  throws  much  light  on  one  of  the  most  important  subjects  which  con- 
fronts the  physiologist,  namely,  the  suitability  of  various  substances 
as  articles  of  diet.  This  subject  we  propose  to  discuss  in  the  present 
chapter,  but  before  doing  so  we  must  lay  down  two  propositions. 

(1)  A  suitable  diet  must  provide  at  least  as  much  of  each  chemical 
element  as  is  excreted  from  the  body. 

(2)  The  daily  food  must  supply  a  store  of  potential  energy  which 
shall  equal  the  actual  energy  dissipated  in  the  twenty-four  hours. 

The  first  of  these  propositions  is  self-evident ;  the  second,  which 
resolves  itself  into  an  enquiry  as  to  whether  the  living  body  obeys 
the  law  of  the  conservation  of  energy,  has  been  the  subject  of  much 
laborious  research. 

In  the  cruder  investigations  of  earlier  workers  (Lavoisier,  etc.),  a 
considerable  discrepancy  appeared  between  the  actual  potential 
energy  of  the  food  taken  in,  and  the  proven  actual  energy  which  is 
dissipated  by  the  body.  More  exact  methods,  especially  in  the 
hands  of  Eubner,  have  gone  far  to  put  the  energy  changes  of  living 
matter  on  a  more  intelligible  basis,  while  investigations  undertaken 
during  the  last  two  decades,  under  the  auspices  of  Atwater,  Benedict, 
and  their  colleagues,  have  finally  established  that  the  law  of  conser- 
vation of  energy  holds  in  relation  to  the  animal  body. 

Among  the  forms  which  energy  derived  from  the  combustion  of 
any  substance,  whether  within  or  without  the  body,  may  assume,  two, 
namely,  mechanical  work  and  heat,  demand  the  attention  of  the 
physiologist.  The  simplest  case  which  can  present  itself,  that  in 


CH.  XLII.] 


CALOR1METRY 


631 


which  the  body  does  no  work,  and  neither  gains  nor  loses  in  weight, 
resolves  itself  into  the  following  problem :  Does  the  heat  given  out 
by  the  body  equal  that  which  would  be  given  out  by  the  complete 
combustion  of  the  various  food  substances,  minus  that  given  out  by 
the  complete  combustion  of  the  excreta  ? 

The  data  necessary  for  settling  such  a  question  are  determined 
by  the  process  known  as  calorimetry. 

The  Bomb  Calorimeter. — The  heat  of  combustion  of  any  of  the 
food  substances  or  of  the  excreta  is  determined  by  placing  a  known 
weight  of  the  substance  in 
question  (A,  fig.  393)  within 
a  bomb  (B)  immersed  in  a 
known  volume  of  water ;  the 
water  is  at  air-temperature 
in  a  brass  vessel  (E),  en- 
closed within  an  ebonite 
casing  (F),  which  acts  as  a 
non-conductor  of  heat.  The 
bomb  is  connected  with  a 
cylinder  of  oxygen  at  high 
pressure;  and  the  sub- 
stance A  is  ignited  by  an 
electric  spark  by  means  of 
the  wires  D.  The  pro- 
ducts of  combustion  pass 
out  through  the  spiral  tube 
C,  and  on  their  journey  give 
off  their  heat  to  the  water. 
If  the  heat  of  combustion 
of  gases  or  volatile  liquids  is 
to  be  determined,  a  special 
form  of  burner  is  introduced 
at  the  opening  at  the  bottom 
of  the  bomb.  When  the 
combustion  is  complete  the 
rise  of  temperature  of  the 
water  is  observed  by  the 
thermometer  T.  During  the 
combustion,  the  water  is  kept  in  movement  by  the  stirrer  S,  which 
is  worked  by  a  small  motor.  The  rise  of  temperature  multiplied  by 
the  weight  of  the  water  gives  the  amount  of  heat  expressed  in  calories, 
1  calorie  or  heat-unit  being  the  quantity  of  heat  necessary  to  raise 
1  gramme  of  water  1°  C. 

Any  given  oxidation  will  always  produce  the  same  amount  of 
heat.     Thus,  if  we  oxidise  a  gramme  of  carbon,  a  known  amount  of 


FIG.  393. — Diagram  of  Bomb  Calorimeter. 
(After  Thomsen.) 


632 


THE   CONSERVATION   OF   ENERGY 


[CH.  XLTT. 


heat  is  produced,  whether  the  element  is  free  or  in  a  chemical  com- 
pound. The  following  figures  show  the  approximate  number  of 
heat-units  produced  by  the  combustion  of  1  gramme  of  the  following 
substances : — 


Hydrogen 
Carbon 
Urea. 
Albumin 


34662 
8100 
2530 
5600 


Fat     . 
Cane  sugar 
Starch 


9400 
3950 
4160 


It  is,  however,  most  important  to  remember  that  the  "  physiologi- 
cal heat- value  "  of  a  food  may  be  different  from  the  "  physical  heat- 
value,"  i.e.,  the  amount  of  heat  produced  by  combustion  in  the  body 
may  be  different  from  that  produced  when  the  same  amount  of  the 
same  food  is  burnt  in  a  calorimeter.  This  is  the  case  with  the  pro- 
teins, because  they  do  not  undergo  complete  combustion  in  the  body, 
for  each  gramme  of  protein  yields  a  third  of  a  gramme  of  urea,  which 
has  a  considerable  heat-value  of  its  own.  Thus  albumin,  which,  by 
complete  combustion,  yields  5600  heat-units,  has  a  physiological 
heat-value  =  5600  minus  one-third  of  the  heat-value  of  urea  (2530) 
=  5600  —  846  =  4754.  Kubner  has  shown  that  this  figure  must  be 
reduced  to  nearly  4000,  as  some  of  the  imperfectly  burnt  products 
of  decomposition  of  proteins  escape  as  uric  acid,  creatinine,  etc.,  in 
the  urine,  and  there  is  a  small  quantity  of  similar  substances  in  the 
faeces.  No  difference  between  the  physical  and  physiological  heat- 
values  of  fats  and  carbohydrates  exists,  provided,  of  course,  that  all 
the  fat  and  carbohydrate  in  the  food  is  absorbed. 

Having  obtained  in  this  way  the  energy  value  of  the  food  taken 
in,  expressed  as  units  of  heat,  th.e  next  step  is  to  arrive  at  the  heat 
produced  in  the  animal  body.  Other  manifestations  of  energy  in  the 
body,  such  as  kinetic  energy,  must  also  be  taken  into  account,  and  it 
is  usual  to  express  these  also  in  terms  of  heat,  one  calorie  being 
equivalent  to  425-5  gramme-metres  (see  p.  129). 

This  is  also  accomplished  by  calorimetry.  From  time  to  time 
numerous  calorimeters  designed  for  this  purpose  have  been  intro- 
duced, but  by  far  the  best  is  the  Atwater-Benedict  instrument,  and 
its  special  value  consists  in  the  circumstance  that  it  can  be  used  for 
making  observations  on  human  beings.  The  method  employed  will 
be  seen  to  be  based  precisely  on  the  same  principles  as  those  of  the 
bomb  calorimeter.  The  apparatus  is  represented  diagrammatically 
in  the  accompanying  drawing  (fig.  394). 

The  Atwater-Benedict  Calorimeter  consists  of  a  room  with  non- 
ducting  walls.  Through  this  run  coils  of  water-pipes,  fitted  with 
metal  ^  discs.  Only  one  of  these  tubes  is  shown  in  the  figure  (A). 
Any  rise  of  the  temperature  of  the  room  is  at  once  taken  up  by  the 
discs  and  communicated  to  the  water.  The  whole  of  the  heat 
production  of  the  individual  in  the  calorimeter  is  therefore  spent 


CH.   XLII.] 


CALORIMETRY 


633 


in  raising  the  temperature  of  the  water.  The  amount  of  water  which 
goes  through  the  pipes  multiplied  by  the  difference  in  the  tempera- 
ture of  the  water  as  it  enters  and  as  it  leaves  the  calorimeter,  gives 
the  heat  output  of  the  person  within  it.  This  is.  ascertained  by  the 
thermometers  (T,  T). 

In  the  case  of  the  bomb  calorimeter  it  is  possible  to  ensure  the 
complete  combustion  of  the  substance  placed  in  the  bomb.  It  is  not 
possible  to  ensure  the  complete  oxidation  of  the  food  eaten.  For 
instance,  food  may  be  retained  and  assimilated  with  a  gain  of  weight 
to  the  individual.  This  is  met  in  the  following  way.  The  air  of  the 
calorimeter  is  kept  circulating  through  a  series  of  chambers  in  which 


Water 


iiiiiiJiiHiiiuiiiiiiiuuiiiiiuiiLiLiii 


Double 
Window. 


Illlllllllllfllllllllllllllllllllllillllll 


•>  Water 


CALORIMETER 
CHAMBER. 


Air  +  Water  +  C02;  deficient  in  Oxygen. 


i 1 

H2S04.  |          |Soda-Lime.| 


LJ 


Air  minus  C02  and  Water;  deficient  in  Oxygen.     » 


Oxygen  enters/ 

Fio.  394.— The  Atwater-Benedict  Calorimeter. 

The  above  drawing  contains  one  mistake ;  the  position  of  the  soda-lime  and  sulphuric  acid 
should  be  transposed. 

the  carbon  dioxide  and  the  water  are  absorbed,  and  subsequently 
estimated.  As  the  oxygen  is  used  up  by  the  individual,  fresh 
oxygen  is  admitted  in  known  quantities.  The  urine  and  faeces  are 
analysed  as  well  as  the  air,  at  the  beginning  and  end  of  the  experi- 
ment. The  following  additional  data  are  therefore  forthcoming : 

(1)  the   carbon,  hydrogen,  and  nitrogen  given   out   by  the   body; 

(2)  the  oxygen  taken  in,  and  from  these  the  amounts  of  protein,  fat, 
and   carbohydrate  metabolised  in  the  body,  can  be  calculated  and 
compared  with  the  food  ingested  (see  p.  613). 

In   the   calorimeter   is   a   bicycle,   the   hind-wheel   of   which  is 
replaced  by  a  copper  disc.     The  disc  may  be  rotated  in  the  field  of 


634 


THE  CONSERVATION  OF  ENERGY 


[CH.  XLII. 


an  electro-magnet  by  the  turning  of  the  pedals,  which  thus  enables 
the  rider  to  perform  a  measurable  quantity  of  mechanical  work. 

The  calorimeter  is  also  supplied  with  a  bed,  a  table,  a  chair,  and 
a  double  window,  through  which  food  of  known  weight  and  com- 
position can  be  supplied,  so  that  an  experiment  may  continue  over 
two  or  three  days,  and  the  effect  of  work,  sleep,  various  diets,  etc., 
can  be  studied. 

Of  the  heat  produced  in  the  body,  it  is  estimated  by  Helmholtz 
that  about  7  per  cent,  is  represented  by  external  mechanical  work, 
and  that  of  the  remainder  about  four-fifths  are  discharged  by  radia- 
tion, conduction,  and  evaporation  from  the  skin,  and  the  remaining 
fifth  by  the  lungs  and  excreta.  This  is  only  an  average  estimate, 
subject  to  much  variation,  especially  in  the  amount  of  work  done. 

The  following  table  exhibits  the  relation  between  the  production 
and  discharge  of  energy  in  twenty-four  hours  in  the  human  organism 
at  rest,  estimated  in  calories.*  The  table  conveniently  takes  the  form 
of  a  balance-sheet  in  which  production  and  discharge  of  heat  are  com- 
pared ;  to  keep  the  body-  temperature  normal  these  must  be  equal. 
The  basis  of  the  table  in  the  left-hand  (income)  side  is  the  same  as 
Voit's  diet  (see  p.  480)  :— 


Production  of  heat. 

Metabolism  of 

Protein  (120  gr.)  .  120  x  4000  = 
Fat(100gr.)  .  100x9400  = 
Carbohydrates  -.  «,„„ 
(  =  333 gr. starch))  ' 


Calories. 
480,000 
940,000 

*«*  9sn 
,385,280 


2,805,280 


Discharge  of  heat. 

Warming  water  in  food, 

2 -6  kilos  x  25°  C.  =       65,000 
Warming  air  in  respiration, 

16  kilos  x  25°  x  0-24=       96,000 
Evaporation  in  lungs, 

630  gr.  x582=  366,660 
Radiation,  evaporation,  etc., 
at  surface,  plus  the  thermal 
equivalent  of  mechanical 
work  done  accounts  for  the 
remainder.  .  .  .  2,277,620 


2,805,280 


The  figures  under  the  heading  Production  are  obtained  by  multi- 
plying the  weight  of  food  by  its  physiological  heat-value.  The 
figures  on  the  other  side  of  the  balance-sheet  are  obtained  as  follows : 
The  water  in  the  food  is  reckoned  as  weighing  2 '6  kilos.  This  is 
supposed  to  be  at  the  temperature  of  the  air,  taken  as  12°  C. ;  it  has 
to  be  raised  to  the  temperature  of  the  body,  37°  C.,  that  is,  through 
25°  C.  Hence  the  weight  of  water  multiplied  by  25  gives  the  number 
of  calories  expended  in  heating  it.  The  weight  of  air  is  taken  as 

*  The  calorie  we  are  taking  is  sometimes  called  the  small  calorie  ;  by  some  the 
word  calorie  is  used  to  denote  the  amount  of  heat  necessary  to  raise  1  kilogramme 
of  water  1°  C.  This  is  called  the  large  calorie. 


CH.  XLTL]  HEAT-VALUE  OF  FOODS  635 

weighing  16  kilos ;  this  also  has  to  be  raised  25°  C.,  and  so  to  be 
multiplied  by  25 ;  it  has  further  to  be  multiplied  by  the  relative  heat 
of  air  (0'24).  The  630  grammes  of  water  evaporated  in  the  lungs 
must  be  multiplied  by  the  potential  or  latent  heat  of  steam  at  37°  C. 
(582) ;  the  portion  of  heat  lost  by  radiation,  conduction,  and  evapora- 
tion from  the  skin  constitutes  about  four-fifths  of  the  whole,  and  is 
obtained  by  deducting  the  three  previous  amounts  from  the  total. 
This  table  does  not  take  into  account  the  small  quantities  of  heat  lost 
with  urine  and  faeces.  If  the  man  does  external  work  the  amount  of 
energy  dissipated  is  increased,  and  he  would,  in  consequence,  require 
more  to  be  supplied  in  the  form  of  food.  Very  few  men  in  active 
work  get  on  well  with  a  smaller  supply  than  3000  large  calories 
(  =  3,000,000  small  calories)  in  their  diet.  A  man,  however,  at  rest 
is  always  doing  what  is  called  internal  work,  that  is,  maintaining 
the  circulation,  respiration,  etc. 

From  experiments  of  this  nature,  it  has  been  found  that  the 
principle  of  the  conservation  of  energy  holds  in  the  living  body. 
The  results  may  be  stated  as  follows : — 

1.  If  an  animal  is  doing  no  external  work,  and  is  neither  gaining 
nor  losing  substance,  the  potential  energy  of  the  food  (expressed  as 
its  heat  of  combustion)  will  be  equal  to  that  of  the  excreta,  plus  that 
given  off  as  heat,  plus  that  of  internal  work. 

2.  If  an  animal  is  doing  external  work,  and  is  neither  gaining 
nor  losing  substance,  the  potential  energy  of  the  food  will  be  equal  to 
the  potential  energy  of  the  excreta,  plus  that  given  off  as  heat,  plus 
that  of  the  internal  work,  plus  that  of  the  external  work. 

3.  If   an   animal  is   doing   no   external   work,   but  gaining   or 
losing  body-substance,  the  potential  energy  of  the  food  will  equal 
the  potential  energy  of  the  excreta,  plus  that  given  off  as  heat,  plus 
that   of   the  internal   work,  plus  that   of   the  gain  by  the  body- 
substance  (a  loss  by  the  body  being  regarded  as  a  negative  gain). 

4.  In  an  animal  doing  external  work,  and  gaining  or  losing  body- 
substance,  the  potential  energy  of  the  food  will  equal  the  potential 
energy  of  the  excreta,  plus  that  given  off  as  heat,  plus  that  of  the 
internal   and   external   work,  plus    that   of   the   gain   (positive  or 
negative)  of  the  body-substance. 


CHAPTER   XLIII 

TEMPERATURE 

SINCE  departures  from  the  normal  body-temperature  are  among 
the  fundamental  physical  signs  of  disease,  and  since  observations  of 
the  temperature  of  the  patient  are  only  less  frequent  in  medical 
practice  than  those  of  the  pulse  or  of  the  tongue,  it  is  necessary  to 
have  as  complete  an  understanding  as  possible  of  the  principles  that 
regulate  the  fluctuations  of  the  clinical  thermometer. 
Animals  may  be  divided  into  two  great  classes  : — 

(1)  Warm-blooded  or  homoiothermal  animals,  or  those  which  have 
an  almost  constant  temperature.     (Mammals  and  birds.) 

(2)  Cold-blooded    or   poikilothermal    animals,    or    those    whose 
temperature  varies   with  that   of  the  surrounding  medium,   being 
always,  however,  a  degree,  or  a  fraction  of  a  degree,  above  that  of  the 
medium.     This   class  includes  reptiles,  amphibians,  fish,  embryonic 
birds  and  mammals,  and  probably  all  invertebrates. 

The  temperature  of  a  man  in  health  varies  but  slightly,  being 
between  36'5°  and  37*5°  C.  (98°  to  99°  F.).  Most  mammals  have 
approximately  the  same  temperature :  horse,  donkey,  ox,  37*5°  to  38° ; 
dog,  cat,  38-5°  to  39° ;  sheep,  rabbit,  38°  to  39'5° ;  mouse,  37'5° ;  rat, 
37'9°.  Birds  have  a  higher  temperature,  about  42°  C.  The  tempera- 
ture varies  a  little  in  different  parts  of  the  body,  that  of  the  interior 
being  greater  than  that  of  the  surface ;  the  blood  coming  from  the 
liver,  where  chemical  changes  are  very  active,  is  warmer  than  that  of 
the  general  circulation ;  the  blood  becomes  rather  cooler  in  its  passage 
through  the  lungs. 

The  temperature  also  shows  slight  diurnal  variations,  reaching  a 
maximum  about  4  or  5  P.M.  (37-5°  C.)  and  a  minimum  about  3  A.M. 
(36-8°  C.) ;  that  is,  at  a  time  when  the  functions  of  the  body  are  least 
active.  If,  however,  the  habits  of  a  man  are  altered,  and  he  sleeps  in 
the  day,  working  during  the  night,  the  times  of  the  maximum  and 
minimum  temperatures  are  also  inverted.  Inanition  causes  the 
temperature^  to  fall,  and  just  at  the  onset  of  death  it  may  be  below 
30°  C.  Active  muscular  exercise  raises  the  temperature  temporarily 
by  about  0-5°  to  1°  C. 


CH.  XLIIL] 


HEAT   PRODUCTION 


637 


Heat  Production. 

(1)  Effect  of  Changes  of  External  Temperature. — In  theory  there  is 
a  fundamental  difference  between  cold-  and  warm-blooded  animals  in 
their  reactions  to  external  temperature.  A  cold  environment,  since 
it  lowers  the  temperature  of  the  poikilothermic  creature,  reduces  the 
metabolism  of  all  its  tissues,  and  thus  reduces  its  heat  production. 

The  warm-blooded  individual  reacts  in  precisely  the  opposite  way. 
Since  his  temperature  remains  constant,  his  heat  production  increases, 
in  order  to  neutralise  the  effect  of  his  cold  surroundings.  This  has 
been  demonstrated  in  the  case  of  fasting  dogs.  An  example  may  be 
given. 


Temperature  of  Air. 

13-8°  C. 

14-7°  C. 

17-3°  C. 

18°  C. 

Heat  production  in  calories 

per  kilo  per  diem   . 

787 

74-7 

69-8 

67-1 

In  practice  it  is  doubtful  whether  any  such  exact  relation  can  be 
discerned  in  man,  as  it  may  be  masked  by  other  factors.  We  have 
already  insisted  upon  the  equality  between  the  respective  energy 
values  of  the  food  eaten  and  of  the  heat  produced,  and  upon  the 
advantage  of  an  ample  diet.  In  practice  it  is  the  amount  of  food 
taken  which  controls  the  heat  production,  rather  than  the  reverse. 
The  majority  of  well-to-do  people,  whose  appetite  is  stimulated  by 
their  palate,  maintain  a  constant  body-temperature  by  regulating 
the  loss  rather  than  the  production  of  heat.  In  this  connection  the 
following  figures,  derived  from  observations  made  upon  a  dog  who 
was  fed  upon  considerable  quantities  of  meat,  may  be  compared  with 
those  obtained  when  the  same  animal  was  fasting. 


Temperature  of  Air. 

7°C. 

15°  C. 

20°  C. 

25°  C. 

30°  C. 

Calories  per  kilo  per  diem  —  dog  \ 
fasting  J 

86-4 

63-0 

55-5 

54'2 

56-2 

Calories  per  kilo  per  diem—  dog  ) 
given  320  g.  meat  -81  calories  per  / 

87-9 

86-6 

76-2 

83-0 

In  the  fasting  dog  a  lowering  of  the  surrounding  temperature, 
increases  heat  production  in  the  animal;  in  the  well-fed  dog  this 
is  hardly  noticeable. 

On  the  other  hand,  it  is  instructive  to  note  the  types  of  food  eaten 
by  the  natives  of  different  climates.  The  Indian,  who  eats  rice  yets 


638  TEMPERATURE  [CH.  XLIII. 

his  carbon  with  less  than  half  the  heat  production  of  the  Esquimaux, 
who  makes  blubber  his  staple  article  of  diet. 

(2)  The  Seat  of  Heat  Production. — So  far  as  our  present  knowledge 
goes,  the  amount  of  metabolism  in  the  bones,  cartilages,  and  connec- 
tive tissues  is  so  small  as  to  form  but  a  trifling  part  of  the  whole 
metabolism  of  the  body.  The  same  is  probably  true  of  unstriped 
muscle.  Of  the  coefficient  of  oxidation  (i.e.  the  amount  of  oxygen 
used  up  per  gramme  of  tissue  per  minute)  of  the  central  nervous 
system  we  have  no  accurate  knowledge.  Any  discussion,  therefore, 
of  the  principal  seats  of  chemical  action  in  the  body  resolves  itself 
into  a  comparison  between  the  glandular  and  muscular  (skeletal) 
structures.  These  present  a  remarkable  contrast.  The  very  vascular 
nature  of  the  secreting  glands  (the  liver  is  said  to  contain  one-quarter 
of  all  the  blood  in  the  body),  as  well  as  actual  measurements  of  the 
oxygen  used  up  by  many  of  them,  indicate  that  they  are  the  seat  of 
very  active  chemical  changes,  which,  relatively  to  muscle,  is  maintained 
with  a  considerable  degree  of  constancy.  The  very  function  which 
the  digestive  glands  serve  implies  at  least  a  certain  constancy  of 
rhythm.  Be  the  climate  what  it  may,  the  daily  food  must  be 
digested.  Quite  otherwise  is  it  with  the  muscles.  When  they  are 
active  they  are  the  seat  of  metabolism  as  great  as  that  of  the  glands,  but 
their  metabolism  is  capable  of  much  more  complete  suspension  during 
rest.  When  the  muscles  are  inactive  the  glandular  structures,  in 
spite  of  their  smaller  bulk,  account  for  a  very  appreciable  quantity 
of  the  whole  metabolism  of  the  body — perhaps  as  much  as  half.  But 
when  the  muscles  are  exercised  to  any  considerable  extent,  the  con- 
tribution of  the  glands  becomes  an  insignificant  item  in  the  met- 
abolism of  the  body.  The  muscles,  then,  by  reason  of  their  large 
mass,  and  of  the  great  variations  of  which  their  metabolism  is  capable, 
are  essentially  the  regulators  of  heat  production. 

Apart  from  active  contraction,  the  muscles  differ  at  different  times 
in  tonus.  This  difference  finds  its  metabolic  expression.  Zuntz,  by 
cutting  the  nerves  of  the  already  resting  leg  of  a  dog,  abolished  the 
muscular  tonus  and  greatly  lessened  the  metabolism.  Alterations 
in  tonus  probably  play  a  very  important  part  in  the  production  of 
heat.  Our  muscles  are  "braced"  in  cold  and  "slack"  in  warm 
climates.  The  latter  effect  is  very  strikingly  shown  by  the  extreme 
muscular  flabbiness  which  evinces  itself  in  such  a  climate  as  that  of 
the  Ked  Sea.  Where  the  cold  is  such  that  increased  tonus  proves 
inadequate  to  meet  the  demand  for  heat,  a  greater  degree  of  muscular 
activity  (shivering)  supervenes  unless  actual  exercise  is  taken. 

Heat  Loss. 

The  two  channels  of  loss  susceptible  of  any  amount  of  variation 
are  the  lungs  and  the  skin.  The  more  air  that  passes  in  and  out 


CH.  XLIIL]  HEAT  LOSS  639 

of  the  lungs,  the  greater  will  be  the  loss  in  warming  the  expired 
air  and  in  evaporating  the  water  of  respiration.  In  such  animals 
as  the  dog,  which  perspire  but  little,  respiration  is  a  most  important 
means  of  regulating  the  temperature;  and  in  these  animals  a  close 
connection  is  observed  between  the  production  of  heat  and  the 
respiratory  activity.  The  panting  of  a  dog  when  overheated  is  a 
familiar  instance  of  this.  A  dog  also,  under  the  same  circumstances, 
puts  out  its  tongue,  and  loses  heat  from  the  evaporation  that 
occurs  from  its  surface.  The  great  regulator,  however,  is  un- 
doubtedly the  skin,  and  this  has  a  double  action.  In  the  first 
place,  it  regulates  the  loss  of  heat  by  its  vaso-motor  mechanism ;  the 
more  blood  passing  through  the  skin,  the  greater  will  be  the  loss  of 
heat  by  conduction,  radiation,  and  evaporation.  Conversely,  the  loss 
of  heat  is  diminished  by  anything  that  lessens  the  amount  of  blood 
in  the  skin,  such  as  constriction  of  the  cutaneous  vessels,  or  dilatation 
of  the  splanchnic  vascular  area.  In  the  second  place,  the  special 
nerves  of  the  sweat-glands  are  called  into  action.  Familiar  instances 
of  the  action  of  these  two  sets  of  nerves  are  the  reddening  of  the 
skin  and  sweating  that  occurs  after  exercise,  on  a  hot  day,  or  in  a 
hot-air  or  vapour  bath,  and  the  pallor  of  the  skin  and  absence  of 
sensible  perspiration  on  the  application  of  cold  to  the  body. 

The  production  of  perspiration  has  a  cooling  effect,  since  the 
latent  heat  necessary  for  the  evaporation  of  the  sweat  is  derived 
chiefly  from  the  body. 

The  relative  importance  of  radiation  and  evaporation  depends 
very  much  upon  the  humidity  of  the  atmosphere.  Here  it  is 
necessary  to  distinguish  between  "relative"  and  "absolute" 
humidity.  The  important  point  is  the  amount  of  water  which  the 
air  can  absorb.  Now,  cold  air,  even  though  it  is  almost  dry,  is 
capable  of  taking  up  very  little  aqueous  vapour.  Warm  air  may 
contain  a  good  deal  (i.e.  the  absolute  humidity  may  be  greater  than 
that  of  the  cold)  and  yet  may  be  far  from  saturated  (i.e.  its  relative 
humidity  may  be  low).  The  loss  of  heat  by  evaporation  is  therefore 
relatively  small  in  cold  weather,  even  though  it  be  dry.  The  burden 
of  heat  regulation  then  falls  upon  radiation,  and  it,  to  be  efficient, 
demands  a  warm  skin ;  hence  the  glow  of  heat  we  experience  when 
we  take  exercise  in  still,  cold  weather. 

In  hot  climates  radiation  becomes  less  important,  and  the 
possibility  of  heat  loss  from  the  skin  therefore  depends  upon 
evaporation.  Evaporation  in  its  turn  depends  upon  the  "  relative  " 
humidity  of  the  air  and  upon  the  existence  of  winds. 

The  loss  of  heat  by  evaporation  is  at  its  maximum  in  dry  hot 
climates,  and  is  greatly  promoted  by  the  wearing  of  clothes  which 
are  relatively  porous.  In  such  climates  physical  "fitness"  is  pro- 
moted by  the  taking  of  a  considerable  amount  of  out-of-door  exercise. 


640  TEMPERATURE  [CH.  XLIII. 

Quite  otherwise  is  it  in  climates  like  that  of  the  coast-line  of 
British  East  Africa,  where  the  tropical  sun  is  combined  with  the 
moisture-laden  wind.  There  the  possibilities  of  heat  loss  both  by 
radiation  and  by  evaporation  are  small,  and  the  English  official  per- 
force reduces  his  heat  production  to  a  minimum.  He  lives  indoors, 
takes  as  little  exercise  as  possible,  and  the  pallor  of  his  countenance 
contrasts  strongly  with  the  high  colour  which  his  colleague  in 
India  or  Egypt  exhibits. 

Certain  Factors  which  govern  the  Relation  between  Heat 
Production  and  Heat  Loss. 

(1)  Size. — The  heat  production  of  the  body,  other  things  being 
equal,  depends  upon  the  mass  of  the  body;  the  heat  loss,  on  the 
surface.     The  production  therefore  varies  with  the  cube  of  the  linear 
dimensions,  whilst  the  loss  of  heat  only  varies  with  the  square. 

The  smaller  the  animal  the  greater  must  be  its  heat  production 
relatively  to  its  heat  loss.  The  loss  of  heat  is  diminished  both  by 
the  occurrence  of  fur  and  by  the  absence  of  sweat  in  the  skins  of 
most  small  animals,  and  the  smaller  the  animal  the  greater  is  its 
metabolism  per  gramme  (see  also  p.  399). 

The  same  is,  no  doubt,  true  of  individuals ;  but  in  this,  as  in  other 
cases,  the  natural  conditions  may  be  much  modified  by  artificial  ones, 
such  as  clothing. 

(2)  Age. — Inasmuch  as  the  young  are  small,  active,  and  growing, 
their   heat  production  is  relatively   large;   and   further,  since  the 
extreme  constancy  of  temperature  which  an  adult  man  has  attained 
is  an  evolved  characteristic,  very  young  children,  in  common  with 
animals,  are  subject  to  changes  of  body-temperature  which  would  be 
of  much  graver  import  in  older  people.     Warm-blooded  animals  in 
the   embryonic   stage   are  practically   cold-blooded,  the  regulatory 
mechanism  which  keeps  the  body-temperature  constant  not  being 
fully  developed  at  this  stage. 

(3)  Constitution. — Different   individuals   differ   greatly   in   their 
power  of  heat  loss.     Apart  from  differences  in  size  and  in  the  faculty 
of  perspiration,  there  remains  such  differences  as  those  of  compactness 
of  shape,  and  especially  in  the  amount  of  adipose  tissue  with  which 
the  viscera  are  protected. 

The  Influence  of  the  Central  Nervous  System  on  Heat  Regulation. 
— The  central  nervous  system  controls  the  loss  of  heat  directly 
through  the  vaso-motor  and  secretory  nerves  supplying  the  skin. 
That  the  control  of  heat  production  is  important,  is  shown  by  the 
effect  on  the  body-temperature  of  cutting  the  spinal  cord,  or  of  the 
drug  curare.  Curare  cuts  off  the  muscles  from  the  stimuli  which 
would  naturally  reach  them  through  the  motor  nerves.  Not  only 


CH.  XLIII.]  FEVER  641 

does  the  temperature  at  once  fall,  but  the  animal  becomes  poikilo- 
thermic. 

The  seat  of  the  heat-regulating  mechanism  in  the  brain  is  a 
matter  of  much  uncertainty.  It  is  possibly  in  the  basal  ganglia  of 
the  cerebrum,  or  in  this  neighbourhood. 

Fever. — Diseases  may  cause  the  temperature  to  vary  considerably, 
especially  those  which  we  term  febrile. 

A  mere  increase  in  the  production  of  heat  does  not  necessarily 
cause  fever.  The  administration  of  food  causes  increased  combustion 
in  the  body ;  but  there  is  no  rise  of  temperature  in  health,  because 
pari  passu  with  the  increased  production  there  is  increased  loss  of 
heat.  Similarly,  diminution  in  the  loss  of  heat,  such  as  occurs  on  a 
hot  as  compared  with  a  cold  day,  does  not  produce  fever,  because  the 
production  of  heat  within  the  body  is  correspondingly  diminished. 
A  febrile  condition  may,  however,  occur  if  tight-fitting  and  otherwise 
unsuitable  clothing  which  interferes  with  the  proper  action  of  the 
skin  is  worn  in  hot  weather ;  this  is  the  frequent  cause  of  "  heat- 
stroke "  among  soldiers  in  the  tropics. 

In  fever  there  is  increased  production  of  heat,  as  is  shown  by 
metabolic  balance-sheets;  the  intake  of  food  is  usually  small,  and 
the  discharge  of  carbon,  nitrogen,  etc.,  results  mainly  from  tissue 
disintegration ;  this  is  even  greater  than  in  ordinary  inanition ;  the 
tissues  are  said  to  be  in  a  "  labile  "  condition,  that  is,  they  are  easily 
broken  down.  Usually  the  skin  is  dry,  the  sweat-glands,  like  most 
of  the  secretory  glands,  being  comparatively  inactive,  and  so  the 
discharge  of  heat  is  lessened.  The  skin,  however,  may  sometimes  be 
bathed  in  perspiration  and  yet  high  fever  be  present.  The  essential 
cause  of  the  high  temperature  in  fever  is  neither  increased  formation 
nor  diminished  discharge  of  heat,  but  an  interference  with  the 
mechanism  which  in  health  operates  so  as  to  equalise  the  two. 

The  Action  of  Drugs. — From  what  has  been  said,  it  will  be  evident 
that  drugs  may  reduce  fever  in  more  than  one  way :  for  instance, 
they  may  reduce  the  metabolism  of  the  muscles,  e.g.  quinine ;  they 
may  cause  increased  heat  loss  by  promoting  perspiration  and 
vascular  dilatation  in  the  skin,  e.g.  pilocarpine ;  or  they  may  act  on 
the  central  heat-regulating  mechanism  (corpus  striatum  ?),  e.g.  phen- 
acetin. 


2  s 


CHAPTER  XLIV 


THE  CENTRAL  NERVOUS    SYSTEM 


THE  central  nervous  system  is  contained  within  the  cranio-spinal 
cavity,  and  consists  of  brain  and  spinal  cord.     These  two  parts  are 


FIG.  395.— Base  of  the  brain.  1,  Superior  longitudinal  fissure ;  2,  2',  2",  anterior  cerebral  lobe ;  3,  fissure 
of  Sylvius,  between  anterior  and  4,  4',  4",  middle  cerebral  lobe  ;  5,  5',  posterior  lobe ;  6,  medulla 
oblongata  ;  the  figure  is  in  the  right  anterior  pyramid  ;  7,  8,  9,  10,  the  cerebellum;  +,  the  inferior 
vermiform  process.  The  figures  from  I.  to  IX .  are  placed  against  the  corresponding  cerebral  nerves ; 
III.  is  placed  on  the  right  crus  cerebri ;  VI.  and  VII.  on  the  pons  Varolii ;  X.  the  first  cervical  or 
suboccipital  nerve.  (Allen  Thomson.)  £. 

continuous  with  one  another,  and  the  line  of  separation  is  arbitrarily 
drawn  at  the  foramen  magnum,  by  which  orifice  the  spinal  cord 
leaves  the  skull.  Both  brain  and  cord  are  enveloped  by  three 

642 


CH.  XLIV.] 


THE  CENTRAL  NERVOUS  SYSTEM 


643 


connective-tissue  membranes,  known  from  without  inwards  as  dura 
mater,  arachnoid,  and  pia  mater  respectively. 

In  Chapter  XVI.  we  have  already  considered  some  of  the 
elementary  and  fundamental  problems  in  relation  to  the  activities  of 
nerve  centres,  and  it  would  be  at  this  point  advisable  that  the 
student  should  refresh  his  memory  on  such  points  by  again  reading 
that  chapter  before  he  proceeds  further. 

The  next  few  chapters  will  deal  with  that  portion  of  the  anatomy 
of  the  spinal  cord  and  brain  which  one  must  know  before  it  is  possible 
to  study  profitably  the  functions  of  these  parts,  and  we  shall  start 
with  the  spinal  cord  and  reach  the  cerebrum  last. 

Before,  however,  passing  on  to  these  details,  a  few  general  words 
are  necessary  in  relation  to  the  construction  of  the  central  nervous 
system  in  vertebrate  animals. 

A  student's  first  glance  at  the  human  brain,  or  at  such  a  drawing 
of  it  as  is  given  in  the  accompanying  figure  (fig.  395),  will  be  sufficient 
to  convince  him  of  its  complicated  structure.  The  next  figure,  how- 
ever, representing  semi-diagrammatically  its  different  parts,  will  make 
an  enumeration  of  its  subdivisions  more  intelligible. 

At  the  lowest  part  of  the  brain  (fig.  396),  continuing  the  spinal 
cord  upwards,  is  the  medulla  oblongata  or  bulb  (D).  Next  comes  the 


FIG.  396.— Plan  in  outline  of  the  brain,  as  seen  from  the  right  side.  £.  The  parts  are  represented  as 
separated  from  one  another  somewhat  more  than  natural,  so  as  to  show  their  connections.  A, 
cerebrum;  /,  g,  h,  its  anterior,  middle,  and  posterior  lobes;  e,  fissure  of  Sylvius;  B,  cerebellum  ; 
C,  pons  Varolii ;  D,  medulla  oblongata ;  a,  peduncles  of  the  cerebrum  ;  b,  c,  d,  superior,  middle,  and 
inferior  peduncles  of  the  cerebellum.  (From  Quain.) 

pons  Varolii  (C),  very  appropriately  called  the  bridge,  because  in  it 
are  the  connections  between  the  bulb  and  the  upper  regions  of  the 


644  THE  CENTRAL  NERVOUS  SYSTEM         [CH.  XLIV. 

brain,  and  between  the  cerebellum  or  small  brain  (B),  and  the  rest  of 
the  nervous  system. 

The  mid-brain  comes  next  (a,  I),  and  this  leads  into  the  peduncles 
or  crura  of  the  cerebrum  (A),  the  largest  portion  of  the  brain. 

Through  the  brain  runs  a  cavity  filled  with  cerebro-spinal  fluid 
and  lined  by  ciliated  epithelium;  this  is  continuous  with  the  central 
canal  of  the  spinal  cord.  In  the  brain,  however,  it  does  not  remain 
a  simple  canal,  but  is  enlarged  at  intervals  into  what  are  called  the 
ventricles.  There  is  one  ventricle  in  each  half  or  hemisphere  of  the 
cerebrum ;  these  are  called  the  lateral  ventricles,  they  open  into  the 
third  ventricle,  which  is  in  the  middle  line ;  and  then  a  narrow  canal 
(aqueduct  of  Sylvius)  leads  from  this  through  the  mid-brain  to  the 
fourth  ventricle,  which  is  placed  on  the  back  of  the  bulb  and  pons, 
which  form  its  floor ;  its  roof  is  formed  partly  by  the  overhanging 
cerebellum,  partly  by  pia  mater.  This  piece  of  pia  mater  is  pierced 
by  a  hole  (Foramen  of  Magendie),  and  so  the  cerebro-spinal  fluid  in 
the  interior  of  the  cerebro-spinal  cavity  is  continuous  with  that  which 
bathes  the  external  surface  of  brain  and  cord  in  the  sub-arachnoid 
space.  The  fourth  ventricle  leads  into  the  central  canal  of  the 
spinal  cord.  Taking  origin  from  the  wall  of  the  cerebral  ventricles, 
and  running  down  the  central  canal  of  the  cord,  is  a  fine  thread 
called  Eeissner's  fibre ;  the  function  of  this  thread  is  entirely 
unknown. 

Speaking  generally,  there  are  two  main  collections  of  grey 
matter — that  on  the  surface,  called  the  cortex,  and  that  in  the  interior, 
bordering  on  the  cerebro-spinal  cavity,  and  subdivided  into  various 
masses  (grey  matter  of  cord,  floor  of  fourth  ventricle,  corpora  striata, 
optic  thalami,  etc.),  whose  closer  acquaintance  we  shall  make  presently. 

But  such  a  complex  brain  as  the  human  brain  does  not  obtain 
throughout  the  vertebrate  series.  The  lower  one  goes  in  the  scale, 
the  less  important  and  large  does  the  cerebrum  become,  until  in  the 
fishes  the  cerebral  hemispheres  are  practically  absent.  It  is  the  large 
size  and  convoluted  grey  cortex  of  these  hemispheres  which  dis- 
tinguishes the  higher  from  the  lower  vertebrates. 

A  comparative  study  of  the  brain  in  different  animals  has  been 
most  valuable  in  the  elucidation  of  the  functions  of  its  various  parts. 

It  is  in  fact  possible  to-day  to  foretell,  if  one  knows  the  habits  of 
an  animal,  what  sort  of  brain  it  possesses  The  converse  is  also 
true ;  given  the  brain  of  an  animal,  one  can  describe  its  habits  and 
mode  of  life  very  fairly  accurately.  For  instance,  animals  which 
rely  largely  on  the  sense  of  smell  for  their  prey  will  have  a  large 
olfactory  area ;  whereas  in  such  animals  as  the  porpoise,  which  have 
no  sense  of  smell,  the  olfactory  area  of  the  brain  is  absent.  Animals 
with  keen  vision  will  have  a  large  visual  area  in  their  brains ,"  animals 
of  nocturnal  habits,  or  who  live  underground  in  the  dark,  will  have 


CH.  XLIV.] 


THE   PRIMITIVE   BRAIN 


645 


a  very  small  one.     A  highly  intellectual  man  has  a  more  elaborately 
convoluted  cerebrum  than  a  savage. 

In  spite  of  these  differences,  and  many  more  might  be  mentioned, 
there  is  throughout  the  vertebrate  series  from 
fish  up  to  man,  the  same  general  plan  of  con- 
struction ;  and  the  brain  of  the  human  embryo 
is  very  much  like  the  adult  condition  of  the 
brain  of  the  fish. 

In  the  foetus  the  central  nervous  system 
is  formed  by  an  infolding  of  a  portion  of  the 
surface  epiblast.  This  becomes  a  tube  of 
nervous  matter,  which  loses  all  connection 
with  the  surface  of  the  body,  though  later 
in  life  this  is  in  a  sense  re-established  by  the 
nerves  that  grow  from  the  brain  and  cord  to 
the  surface.  The  anterior  end  of  this  tube 
becomes  greatly  thickened,  to  form  the 
brain,  its  cavity  becoming  the  cerebral  ven- 
tricles ;  the  rest  of  the  tube  becomes  the 
spinal  cord.  The  primitive  brain  is  at  first 
subdivided  into  three  parts,  the  primary 
cerebral  vesicles;  the  first  and  third  of  these 
again  subdivide,  so  that  there  are  ultimately 
fivs  divisions,  which  have  received  the 
following  names : — 

1.  Pros-encephalon,  telencephalon  or  fore- 
brain.     This  is  developed  into  the  cerebrum 
with  the  corpora   striata.      It   encloses   the 
lateral  ventricles. 

2.  Thalam-encephalon,  diencephalon,    or 
twixt  brain.     This  is  developed  into  the  parts 
including   the   optic   thalami,  which  enclose 
the  third  ventricle. 

3.  Mes-encephalon,    or    mid-brain,    con- 
sists of  the  parts  which  enclose   the  aque- 
duct    of     Sylvius  —  namely,     the     corpora 
quadrigemina,   which    form   its    dorsal,   and 
the   crura   cerebri,   which    form    its   ventral 
aspect.     The  corpora  quadrigemina  in  many 
lower  animals  instead  of  being  four  in  number 
are  two,  and  are  called  the  optic  lobes. 

4.  Met-encephalon,  or  hind-brain,  which  forms  the  cerebellum 
and  pons. 

5.  Myel-encephalon,  or   after-brain,  which    forms  the  bulb   or 
medulla  oblongata. 


M.o. 


FIG.  397.— Diagrammatic  hori- 
zontal section  of  a  vertebrate 
brain.  The  figures  serve  both 
for  this  and  the  next  diagram. 
Afb,  mid-brain  :  what  lies  in 
front  of  this  is  the  fore-,  and 
what  lies  behind,  the  hind- 
brain ;  Lt,  lamina  terminalis  ; 
Olf,  olfactory  lobes ;  Hmp, 
hemispheres ;  Th.  E,  thalam- 
encephalon ;  Pn,  pineal 
gland  ;  Py,  pituitary  body  ; 
P.M.,  foramen  of  Munro ;  cs, 
corpus  striatum ;  TA,  optic 
thalamus  ;  CC,  crura  cerebri  : 
the  mass  lying  above  the  canal 
represents  the  corpora  quad- 
rigemina ;  Cb,  cerebellum ; 
M.o.,  medulla  oblongata; 
/ — IX,  nine  pairs  of  cranial 
nerves ;  1,  olfactory  ventri- 
cle ;  2,  lateral  ventricle ; 
8,  third  ventricle ;  4,  fourth 
ventricle ;  + ,  iter  a  tertio 
ad  quartum  ventriculum,  or 
aqueduct  of  Sylvius. 

(Huxley.) 


646 


THE   CENTRAL  NERVOUS   SYSTEM 


[CH.  XL1V. 


Figs.  397  and  398  represent  a  diagrammatic  view  of  a  vertebrate 
brain;  the  attachments  of  the  pineal  gland,  pituitary  body,  and 
olfactory  (I)  and  optic  (II)  outgrowths  are  also  shown. 


Fro.  398.— Longitudinal  and  vertical  diagrammatic  section  of  a  vertebrate  brain.  Letters  as  before. 
I'V,  poris  Varolii.  Lamina  terminalis  is  represented  by  the  strong  black  line  joining  Pn  and  Py. 
(Huxley.) 

These  diagrams  might  serve  very  well  for  the  brain  of  an  adult 
selachian  fish,  such  as  a  shark.  The  olfactory  bulb  is,  however,  very 
much  larger,  and  the  fore-brain  smaller.  In  the  shark,  smell  is  the 
all-important  sense ;  the  olfactory  nerves,  which  originate  from  the 
olfactory  bulb,  spread  out  over  an  immense  area  many  square  feet  in 
size  (12  to  13  square  feet  in  a  shark  25  feet  long).  Behind  the 
olfactory  bulb  is  another  focus  of  grey  matter,  called  by  Edinger  the 
parolfactory  lobe,  connected  to  the  fifth  nerve,  the  sensory  nerve  of 
the  mouth.  No  doubt  the  oral  sense,  as  it  is  termed,  is  important  in 
the  pursuit  and  capture  of  prey ;  it  always  is  in  animals  who  catch 
food  with  the  mouth.  One  sees  it  highly  developed  in  animals  with 
prehensile  tongues,  and  bristles  or  whiskers  on  the  lips ;  also  in  birds, 
with  their  sensitive  beaks  and  bills. 

Returning,  however,  to  the  shark,  we  find  the  cerebellum  is  large, 
as  it  is  in  all  powerful  swimmers  and  flyers,  but  the  cerebrum  in  the 
strict  sense  is  absent ;  there  are  no  hemispheres  and  no  grey  cortex ; 
the  fore-brain  consists  of  little  else  but  the  corpora  striata. 

The  cerebral  hemispheres  are  later  growths  superimposed  upon 
this  primitive  brain,  and  in  the  animal  series  one  notes  the  progres- 
sive development  of  the  cerebrum  in  relation  to  function  and  adapta- 
tion to  environment. 

The  primitive  brain  as  exemplified  in  that  of  the  shark  is  common 
to  all  animals  up  to  man,  and  is  termed  by  Edinger  the  Pala- 
encephalon  or  old  brain.  The  cerebral  hemispheres  constitute  what 
he  terms  the  Neo-encephalon  or  new  brain. 

The  neo-encephalon  is  specially  characterised  by  the  possession 
of  a  grey  cortex,  and  this  is  the  seat  of  the  psychical  or  mental 
processes  termed  volition  and  sensation.  The  first  part  of  the  cortex 
to  appear  in  development  is  called  the  archipallium  (or  old  cortex), 


CH.  XLIV.] 


THE   ARCHIPALLIUM   AND   NEOPALLIUM 


647 


and  this  is  associated  with  smell,  the  most  important  sense  in  the 
old  primitive  brain.  The  rest  of  the  cortex  is  termed  the  neopallium 
(or  new  cortex) ;  it  subserves  the  functions  of  hearing,  vision,  touch, 
and  the  muscular  sense,  and  is  also  concerned  in  the  origination  of 
those  volitions  which  result  in  movements  initiated  and  guided  by 
those  senses.  The  progressive  development  of  the  neopallium  is 
especially  marked  in  the  primates  and  in  man,  for  in  these  the  more 
primitive  olfactory  and  oral  senses  are  unimportant  in  the  struggle 
for  existence ;  in  man  the  receptive  olfactory  membrane  in  the  nose 
measures  considerably  less  than  a  square  inch  instead  of  the  many 
square  feet  it  extends  over  in  the  shark ;  but  the  visual  and  other 
faculties  enumerated  become  preponderatingly  important  as  associa- 
tive memory  develops  and  the  brain  becomes  the  organ  of  mind. 
The  structure  of  the  neopallium  is  more  elaborate  than  that  of  the 
archipallium. 

The  following  table  will  make  the  relationship  of  these  parts 
clear  :— 

THE  VERTEBRATE  BRAIN 
consists  of 


The     Pala-encephalon, 
old  primitive  brain. 


The  Neo-encephalon,  or  new  brain. 
This  consists  of  the  cerebral  cor- 
tex (with  its  efferent  and  afferent 
fibres)  and  may  be  subdivided  into 


a.  The  Archipallium^   or 
old  cortex. 


6.  The  Neopallium,  or 
new  cortex. 


CHAPTEE  XLV 

STRUCTURE  OF  THE  SPINAL  CORD 

THE  spinal  cord  is  a  column  of  nerve-substance  connected  above  with 
the  brain  through  the  medium  of  the  bulb,  and  situated  in  the  spinal 
canal.  In  transverse  section  it  is  approximately  circular,  but  the 
cord  is  not  of  the  same  size  throughout  its  course.  It  exhibits  two 
enlargements,  one  in  the  cervical,  the  other  in  the  lumbar  region. 
These  are  the  situations  whence  the  large  nerves  for  the  supply  of 
the  limbs  issue.  The  cord  ends  below,  about  the  lower  border  of  the 
first  lumbar  vertebra,  in  a  cone-shaped  termination  (the  conus 
medullaris)  from  which  passes  a  slender  filament  of  grey  substance, 
the  filum  terminate,  which  lies  in  the  midst  of  the  roots  of  many 
nerves  forming  the  cauda  equina. 

It  is  composed  of  grey  and  white  matter ;  the  white  matter  is 
situated  externally,  and  constitutes  its  chief  portion ;  the  grey  matter 
is  in  the  interior,  and  is  so  arranged  that  in  a  transverse  section  of 
the  cord  it  appears  like  two  crescentic  masses  (the  horns  of  each  of 
which  are  called  respectively  the  anterior  and  posterior  cornua)  con- 
nected together  by  a  narrower  portion  or  isthmus,  called  the  posterior 
commissure  (fig.  399).  Passing  through  the  centre  of  this  isthmus 
in  a  longitudinal  direction  is  a  minute  canal ;  in  a  transverse  section 
it  appears  as  a  hole ;  this  central  canal  of  the  spinal  cord  is  continued 
throughout  its  entire  length,  and  opens  above  into  the  space  at  the 
back  of  the  medulla  oblongata  and  pons  Varolii,  called  the  fourth 
ventricle. 

The  spinal  cord  consists  of  two  symmetrical  halves,  separated 
anteriorly  and  posteriorly  by  vertical  fissures  (the  posterior  fissure 
being  deeper,  but  less  wide  and  distinct  than  the  anterior),  and 
united  in  the  middle  by  nervous  matter  which  is  usually  described 
as  forming  two  commissures — an  anterior  commissure  (consisting  of 
medullated  nerve-fibres)  in  front  of  the  posterior  commissure,  which 
is  the  isthmus  of  grey  matter  pierced  by  the  central  canal,  to  which 
we  referred  in  the  last  paragraph  (fig.  399,  B).  Each  half  of  the  spinal 
cord  is  marked  on  the  sides  (obscurely  at  the  lower  part,  but  dis- 

648 


CH.  XLV.] 


STRUCTURE   OF   THE   SPINAL   CORD 


649 


tinctly  above)  by  two  longitudinal  furrows,  which  divide  it  into  three 
portions,  columns,  or  tracts,  an  anterior,  lateral,  and  posterior.  From 
the  groove  between  the  anterior  and  lateral  columns  spring  the 
anterior  roots  of  the  spinal  nerves  (fig.  399,  B  and  c,  5) ;  and  just 
in  front  of  the  groove  between  the  lateral  and  posterior  column  the 


FIG.  399.— Different  views  of  a  portion  of  the  spinal  cord  from  the  cervical  region,  with  the  roots  of  the 
nerves  (slightly  enlarged).  In  A,  the  anterior  surface  of  the  specimen  is  shown  ;  the  anterior  nerve- 
root  of  its  right  side  is  divided ;  in  B,  a  view  of  the  right  side  is  given ;  in  c,  the  upper  surface  is 
shown  ;  in  r>,  the  nerve-roots  and  ganglion  are  shown  from  below.  1,  the  anterior  median  fissure ; 
2,  posterior  median  fissure  ;  3,  anterior  lateral  depression,  from  which  the  anterior  nerve-roots  are 
seen  to  issue ;  4,  posterior  lateral  groove,  into  which  the  posterior  roots  are  seen  to  sink ;  5, 
anterior  roots  passing  the  ganglion  ;  5',  in  A,  the  anterior  root  divided  ;  6,  the  posterior  roots,  the 
fibres  of  which  pass  into  the  ganglion  6' ;  7,  the  united  or  compound  nerve  ;  7',  the  posterior  primary 
branch,  seen  in  A  and  D  to  be  derived  in  part  from  the  anterior  and  in  part  from  the  posterior  root. 
(Allen  Thomson.) 

posterior  roots  enter  (B,  6) :  a  pair  of  roots  on  each  side  corresponds 
to  each  vertebra. 

White  matter. — The  white  matter  of  the  cord  is  made  up  of 
medullated  nerve-fibres,  of  different  sizes,  running  mainly  in  a 
longitudinal  direction,  and  of  a  supporting  material  of  two  kinds, 
viz. : — (#)  ordinary  fibrous  connective  tissue  with  elastic  fibres,  which 
is  connected  with  septa  from  the  pia  mater  which  pass  into  the  cord 
to  carry  the  blood-vessels,  (b)  Neuroglia;  the  processes  of  the 
neuroglia-cells  are  arranged  so  as  to  support  the  nerve-fibres,  which 
are  without  the  usual  neurilemmal  nerve-sheaths. 

The  general  rule  respecting  the  size  of  different  parts  of  the  cord 
is,  that  each  part  is  in  direct  proportion  to  the  size  and  number  of 
nerve-roots  given  off  from  it.  Thus  the  cord  is  very  large  in  the 


650 


STRUCTURE   OF  THE   SPINAL   CORD 


[CH.  XLV. 


middle  and  lower  part  of  its  cervical  portion,  whence  arise  the  large 
nerve-roots  for  the  formation  of  the  brachial  plexuses  and  the  supply 
of  the  upper  extremities ;  it  again  enlarges  at  the  lowest  part  of  its 
dorsal  portion  and  the  upper  part  of  its  lumbar,  at  the  origins  of  the 
large  nerves  which,  after  forming  the  lumbar  and  sacral  plexuses,  are 
distributed  to  the  lower  extremities.  The  chief  cause  of  the  greater 
size  at  these  parts  of  the  spinal  cord  is  increase  in  the  quantity  of 
grey  matter;  the  white  part  of  the  cord  (especially  the  lateral 
columns)  becomes  gradually  and  progressively  smaller  from  above 
downwards,  because  a  certain  number  of  fibres  coming  down  from  the 
brain  pass  into  the  spinal  grey  matter  at  different  levels. 

Grey  matter. — The  grey  matter  of  the  cord  consists  of  nerve- 
fibres,  most  of  which  are  very  fine  and  delicate,  of  nerve-cells  with 
branching  processes,  and  of  an  extremely  delicate  network  of  the 
primitive  fibrillae  of  axis-cylinders  and  of  dendrites.  This  fine  plexus 
is  called  Gferlactis  network,  and  is  mingled  with  the  meshes  of 
neuroglia.  The  neuroglia  of  the  grey  matter  resembles  that  of  the 
white,  but  instead  of  everywhere  forming  a  close  network  to  support 
the  nerve-fibres,  here  and  there  it  is  in  the  form  of  a  more  open 
sponge-work  to  support  the  nerve-cells.  It  is 
especially  developed  around  the  central  canal, 
which  is  lined  with  columnar  ciliated  epi- 
thelium, the  cells  of  which  at  their  outer  ends 
terminate  in  fine  processes,  which  join  the 
neuroglia  network  surrounding  the  canal,  and 
form  the  substantia  gelatinosa  centralis.  It  is 
also  developed  at  the  tip  of  the  posterior  cornu 
of  grey  matter,  forming  what  is  known  as  the 
substantial,  gelatinosa  lateralis  of  Eolando,  which 
is  much  enlarged  in  the  upper  cervical  region. 

Groups  of  cells  in  the  grey  matter. — The 
multipolar  cells  of  the  grey  matter  are  either 
scattered  singly  or  arranged  in  definite  groups 
(see  fig.  400). 

(1)  Anterior  horn  cells. — In  the  cervical  and 
lumbar  enlargements  there  are  several  groups 
of  large  multipolar  cells  in  the  anterior  horn ; 
in  bhe  thoracic  region  these  are  reduced  to  two, 
a  mesial  and  a  lateral  group.  The  larger  groups  correspond  with 
segments  of  the  limbs,  and  in  the  cervical  cord  there  is  one  special 
group  from  which  the  phrenic  nerve  arises  for  the  supply  of  the 
diaphragm.  The  axons  pass  out  by  the  anterior  nerve-roots  of  the 
same  side,  but  a  few  axons  pass  to  the  antero-lateral  column  of  the 
same  side,  and  by  the  white  commissure  to  that  of  the  opposite  side. 
In  birds,  a  few  axons  are  stated  to  pass  to  the  posterior  roots. 


FIG.  400.— Section  of  half  the 
spinal  cord  to  show  the 
principal  groups  of  cells  in 
the  grey  matter ;  a,  groups 
of  cells  in  the  anterior 
horn  ;  c,  Clarke's  column  ; 
i,  intermedio-lateral  group ; 
m,  middle  cell  column  ;  p, 
scattered  cells  of  the  pos- 
terior horn.  (Diagrammatic 
after  Schafer.) 


CH.  XLV.]  TRACTS   IN   THE  SPINAL   CORD  651 

(2)  Posterior  vesicular  column  of  Lockhart  Clarke ;  generally  known 
as  Clarke's  column. — This  is  a  group  of  large  nerve-cells  with  their  long 
axis  vertical.     It  lies  at  the  base  of  the  posterior  horn,  and  is  best 
marked  in  the  thoracic  region.     The  axons  of  these  cells  pass  into 
the  cerebellar  tracts. 

(3)  Intermedio-lateral  group. — This  is  seen  in  the  outer  part  of 
the  grey  matter  of  the  lateral  horn,  and  is  most  distinct  in  the  upper 
thoracic  and  lower  cervical  regions. 

(4)  The  middle  cell  column  lies  in  the  middle  of  the  crescent. 

(5)  The  cells  of  the  posterior  horn  are  usually  small ;    they  are 
numerous,  but  are  not  disposed  in  special  groups. 

Columns  and  tracts  in  the  white  matter  of  the  spinal  cord. — The 
columns  of  the  white  matter  which  are  marked  out  by  the  points 
from  which  the  nerve-roots  issue,  are  called  the  anterior,  the  lateral, 
and  the  posterior  columns;  the  posterior  is  further  divided  by  a 
septum  of  the  pia  mater  into  two  almost  equal  parts,  constituting 
the  postero-external  column,  or  column  of  Burdach,  and  the  postero- 
median,  or  column  of  Goll  (fig.  402).  In  addition  to  these  columns, 
however,  it  has  been  shown  that  the  white  matter  can  be  still  further 
subdivided.  These  tracts  in  the  white  matter  perform  different 
functions  in  the  conduction  of  impulses. 

These  tracts  have  been  made  out  by  the  following  methods : — 

(a)  The  emlryological  method.     It  has  been  found  by  examining 
the  spinal  cord  at  different  stages  of  its  development  that  certain 
groups   of   the  nerve-fibres  put  on   their  myelin  sheath   at  earlier 
periods    than    others,  and   so   the   different   groups    of    fibres   can 
be  easily   distinguished.     This  is   also    known   as   the  method   of 
Flechsig. 

(b)  Wallerian  or  degeneration  method. — This  method  depends  upon 
the  fact  that  if  a  nerve-fibre  is  separated  from  its  nerve-cell,  it  wastes 
or  degenerates.      It  consists  in   tracing  the   course   of   tracts   of 
degenerated  fibres,  which  result  from  an  injury  to  any  part  of  the 
central  nervous  system.     When  fibres  degenerate  below  a  lesion,  the 
tract  is  said  to  be  of  descending  degeneration,  and  when  the  fibres 
degenerate  in  the  opposite  direction,  the  tract  is  one  of  ascending 
degeneration.     By  the  modern  methods   employed  in   staining   the 
central  nervous  system,  it  has  proved  comparatively  easy  to  distinguish 
degenerated  parts  in  sections  of  the  cord  and  of  other  portions  of  the 
central  nervous  system.     Degenerated  fibres  have  a  different  staining 
reaction  when  the  sections  are  stained  by  what  are  called  Weigert's 
and  Pal's  methods;    this  consists  in   subjecting  them  to  a  special 
solution  of  hsematoxylin,  and  then  to  certain  differentiating  solutions. 
The  degenerated  fibres  appear  light  yellow,  whereas  the  healthy  fibres 
are  a  deep  blue.     Marchi's  method  is  even  better.     After  hardening 
in  Miiller's  fluid,  Marchi's  solution  (a  mixture  of  Miiller's  fluid  and 


652  STRUCTURE   OF  THE   SPINAL   CORD  [CH.  XLY. 

osmic  acid)  stains  degenerated  fibres  black,  and  leaves  the  rest  of  the 
tissue  unstained.  Accidents  to  the  central  nervous  system  in  man 
have  given  us  much  information  upon  this  subject,  but  this  has  of 
late  years  been  supplemented  and  largely  extended  by  experiments 
on  animals,  particularly  upon  monkeys ;  and  considerable  light  has 
been  shed  upon  the  conduction  of  impulses  to  and  from  the  nervous 
system  by  the  study  of  the  results  of  section  of  different  parts  of 
the  central  nervous  system,  and  of  the  spinal  nerve-roots. 

By  these  methods  the  tracts  in  the  white  matter  have  now  been 
mapped  out,  and  the  principal  ones  are  shown  in  the  succeeding 
diagrams. 

It  will  be  convenient  to  begin  by  considering  the  result  of  cutting 
through  the  roots  of  the  spinal  nerves. 

Cutting  the  anterior  roots  produces  chromatolysis  of  the  cells  of 
the  anterior  horn  from  which  they  originate ;  this  slow  atrophy  is  the 
result  of  disuse  of  the  axons  which  are  cut  and  still  remain  attached  to 
the  cell-bodies.  Wallerian  degeneration  is  limited  to  the  motor  nerve- 
fibres  on  the  distal  side  of  the  point  of  section.  The  fact  that  chro- 
matolysis (see  p.  193)  occurs  when  the  axon  of  a  nerve-cell  is  cut 
through,  furnishes  us  with  a  valuable  method  of  ascertaining  from 
what  nerve-cells  various  tracts  originate. 

Cutting  the  posterior  roots  between  the  spinal  ganglia  and  the 
cord  leaves  the  peripheral  part  of  the  nerve  healthy,  and  degeneration 
occurs  in  the  portion  of  the  root  which  runs  into  the  cord,  because 
the  fibres  are  cut  off  from  the  cells  of  the  spinal  ganglion  from  which 
they  grew.  These  degenerated  nerve-fibres  may  be  traced  up  the 
cord  for  a  considerable  distance.  Each  posterior  root-fibre  when  it 
enters  the  cord  bifurcates,  the  main  branch  passing  upwards,  and  the 
shorter  branch  downwards,  so  that  the  degeneration  is  seen  in  a 
small  tract  called  the  comma  tract  (fig.  403)  immediately  below  the 
point  of  entrance  of  the  cut  posterior  root.  The  upgoing  fibre  is 
contained  in  the  posterior  column  of  white  matter,  and  it  terminates 
in  the  grey  matter  either  in  the  cord  itself  at  a  higher  level,  or  in 
the  medulla  oblongata. 

Fig.  401  represents  in  a  schematic  way  the  manner  in  which  the 
fibres  of  the  two  roots  of  a  spinal  nerve  are  connected  to  the  grey 
matter  in  the  cord. 

1,  2,  3,  4  represent  four  cells  of  the  anterior  horn.  Each  gives 
rise  to  an  axis-cylinder  process  A,  one  of  which  is  shown  terminating 
in  its  final  ramification  in  the  end-plate  of  a  muscular  fibre  M.  Each 
of  these  four  cells  is  further  surrounded  by  an  arborisation  (synapse) 
derived  from  the  fibres  of  the  pyramidal  tract  P,  which  comes  down 
from  the  brain.  The  pyramidal  fibres  really  terminate  around  the 
cells  at  the  base  of  the  posterior  horn ;  these  cells  therefore  act  as 
intermediate  cell-stations  on  the  way  to  those  in  the  anterior  horn. 


CH.  XLV.] 


ROOTS   OF   THE   SPINAL   NERVES 


653 


These    are    omitted    from    the  diagram    to   avoid   confusion   (see, 
however,  fig.  185,  p.  190). 

A  fibre  of  the  posterior  root  is  also  shown ;  this  originates  from 
the  cell  G  of  a  spinal  ganglion ;  the  process  of  this  cell  bifurcates, 
one  branch  (B)  passing  to  the  periphery,  where  it  ends  in  an  arbor- 
escence  in  the  skin  (S) ;  the  arrow  by  the  side  of  this  branch 
represents  the  direction  of  conduction  of  the  sensory  impulses  from 
the  skin.  An  arrow  in  the  opposite  direction  would  indicate  the 
direction  of  its  growth.  The  other  branch  (C)  passes  into  the  spinal 


FIG.  401.— Course  of  nerve-fibres  in  spinal  cord.    (After  Sch.afer.) 

cord,  where  it  again  bifurcates;  the  branch  E,  a  short  one,  passes 
downwards  and  ends  in  an  arborisation  around  one  of  the  small  cells 
(Pj)  of  the  posterior  cornu ;  from  which  a  new  axis-cylinder  arises, 
and  terminates  around  one  or  more  of  the  multipolar  cells  (4)  of  the 
anterior  horn. 

The  main  division  D  travels  up  in  the  posterior  column  of  the 
cord,  and  ends  in  grey  matter  at  various  levels.  Some  collaterals  (5) 
possibly  terminate  by  arborising  directly  around  the  anterior  cornual 
cells,  principally  of  the  same  side ;  others  (6)  do  so  with  an  intermediate 
cell-station  in  a  posterior  cornual  cell  (Pa)  ;  others  (7)  arborise  around 
the  cells  of  Clarke's  column  (C)  in  the  thoracic  region  of  the  cord, 


654 


STRUCTURE  OF  THE   SPINAL   CORD 


[CH.  XLV. 


Goll 


and  from  these  cells  fresh  axis-cylinders  carry  up  the  impulse  to  the 
cerebellum  in  what  are  called  the  cerebellar  tracts,  while  the  main 
fibre  (8)  may  terminate  in  any  of  these  ways  at  a  higher  level 
in  the  cord,  or  above  the  cord  in  the  medulla  oblongata.  A  certain 
number  of  posterior  root -fibres,  however,  cross  the  middle  line  and 
pursue  their  way  up  to  the  bulb  in  the  ascending  tracts  of  the 
opposite  side  of  the  cord. 

In  general  terms  the  anterior  root-fibres  pass  out  of  the  grey 
matter  of  the  anterior  horns,  and  after  a  short  course  leave  the  spinal 
cord  in  the  anterior  spinal  nerve-roots.  The  posterior  roots,  on  the 
other  hand,  do  not  pass  to  any  great  extent  into  the  grey  matter 

immediately,  but  into  the  white 
matter  on  the  inner  side  of  the 
posterior  horn ;  in  other  words, 
they  go  into  the  column  of 
Burdach  (fig.  402);  they  pass 
up  in  this  column,  but  gradu- 
ally approach  the 'middle  line, 
and  are  continued  upwards  to 
the  medulla  in  the  column  of 
Goll;  but  as  they  go  up  they 
become  less  numerous,  as  some 
terminate  in  the  grey  matter  of 
the  cord  on  the  way  in  the 
manner  described.  A  few  fibres 
of  the  posterior  root,  however, 
travel  for  a  short  distance  in  a 
small  tract  on  the  outer  side  of  the  posterior  horn ;  this  is  called  the 
tract  of  Lissauer  (fig.  404);  the  comma  tract  (fig.  403)  has  been 
already  explained. 

Suppose  now  one  cuts  through  several  posterior  roots  between  the 
spinal  ganglia  and  the  cord,  so  that  the  course  of  degeneration  may 
be  more  readily  traced.  Immediately  below  the  points  of  entrance  of 
these  nerve-roots,  the  comma  tract  will  be  found  degenerated ;  imme- 
diately above,  the  degenerated  fibres  will  be  found  in  the  column  of 
Burdach ;  higher  up  in  the  cord  they  will  be  less  numerous,  and  have 
approached  the  middle  line ;  the  fibres  which  enter  the  cord  lowest 
get  ultimately  nearest  the  middle  line,  so  that  the  greater  part  of  the 
column  of  Goll  is  made  up  of  sensory  fibres  from  the  legs ;  the  fibres 
which  enter  the  cord  last,  for  instance  those  from  the  upper  limbs 
and  neck,  pursue  their  upward  course  in  the  column  of  Burdach. 

The  preceding  figure  (fig.  402)  shows  the  degeneration  in  a  section 
of  the  spinal  cord,  after  the  division  of  a  number  of  nerve-roots  on 
one  side.  The  microscopic  section  is  taken  high  up,  so  that  all  the 
degenerated  fibres  have  passed  into  the  column  of  Goll  on  the  same 


FIG.  402. — Degeneration  in  column  of  Goll  after 
section  of  posterior  nerve-roots. 


CH.  XLV.]  DEGENERATION   TRACTS  655 

side ;  the  inner  set  (1)  are  shaded  differently  from  the  outer  set  (2), 
indicating  that  those  nearest  the  middle  line  come  from  the  lowest 
nerve-roots.  Those  which  cross  to  the  opposite  side  soon  after 
entrance  into  the  cord,  are  not  shown ;  they  will  be  found  forming  a 
scattered  degeneration  in  the  ascending  tracts  of  the  other  side. 

We  may  pass  from  this  to  consider  the  tracts  of  degeneration 
that  occur  when  the  spinal  cord  is  cut  right  across  in  the  thoracic 
region.  Some  tracts  will  be  found  degenerated  in  the  piece  of  cord 
below  the  lesion;  these  consist  of  nerve-fibres  that  are  connected 
with  the  nerve-cells  in  the  brain ;  the  principal  ones  are  the  pyramidal 
bracts.  Other  tracts  are  found  degenerated  in  the  piece  of  cord 
above  the  lesion;  these  consist  of  nerve-fibres  that  are  connected 
with  the  nerve-cells  of  the  spinal  ganglia,  or  with  the  cells  of  the 
spinal  cord  itself  below  the  lesion,  and  are  passing  upwards. 

In  general  terms  we  may  say  that  the  tracts  which  degenerate 
downwards  are  the  motor  tracts,  and  those  which  degenerate  upwards 
are  the  afferent  or  sensory  channels.  We  must  also  take  into 
account  groups  of  association  fibres  which  unite  together  different 
regions  of  the  cord ;  these  are  generally  short  tracts  in  which,  there- 
fore, degeneration  can  only  be  traced  a  short  distance  up  or  down. 
The  long  tracts  are  those  which  connect  cord  or  spinal  nerves  with 
brain,  such  as  those  of  Goll  and  Burdach  just  mentioned,  or  the 
pyramidal  tracts  the  main  efferent  pathways. 

Tracts  of  Descending  Degeneration  (fig.  403). 

(1.)  The  crossed  pyramidal  tract. — This  is  situated  in  the  lateral 
column  on  the  outer  side  of  the  posterior  cornu  of  grey  matter.  At 
the  lower  part  of  the  spinal  cord  it  extends  to  the  margin,  but  higher 
up  it  becomes  displaced  from  this  position  by  the  interpolation  of 
another  tract  of  fibres,  to  be  presently  described,  viz.,  the  direct 
cerebellar  tract.  The  crossed  pyramidal  tract  is  large,  and  may 
touch  the  grey  matter  at  the  tip  of  the  posterior  cornu,  but  is 
separated  from  it  elsewhere.  Its  shape  on  cross-section  is  somewhat 
like  a  lens,  but  varies  in  different  regions  of  the  cord,  and  diminishes 
in  size  from  the  cervical  region  downwards,  its  fibres  passing  off  as 
they  descend,  to  arborise  around  the  nerve-cells  in  the  grey  matter  of 
the  cord.  The  fibres  of  which  this  tract  is  composed  are  moderately 
large,  but  are  mixed  with  some  that  are  smaller. 

(2.)  The  direct  or  uncrossed  pyramidal  tract,  or  column  of  Tilrck. — 
This  is  situated  in  the-  anterior  column  by  the  side  of  the  anterior 
fissure.  It  ends  in  the  mid  or  lower  thoracic  region  of  the  cord. 

The  two  pyramidal  tracts  come  down  from  the  brain ;  in  the 
medulla  oblongata,  the  greater  number  of  the  pyramidal  fibres  cross 
over  to  the  other  side  of  the  cord,  which  they  descend ;  hence  the 
term  crossed  pyramidal  tract ;  a  smaller  collection  of  the  pyramidal 


656 


STRUCTURE  OF  THE   SPINAL   CORD 


[CH.  XLV. 


fibres  goes  straight  on,  on  the  same  side  of  the  cord,  and  these  cross 
at  different  levels  in  the  anterior  commissure  of  the  cord  lower  down  ; 
hence  the  disappearance  of  the  direct  pyramidal  tract  in  the  lower 
part  of  the  cord.  The  fact  that  the  crossed  pyramidal  tract  of  one 
side  is  the  fellow  of  the  direct  pyramidal  tract  of  the  other  side,  is 
indicated  in  the  diagram  by  the  direction  of  shading  (see  fig.  403). 


Comma  tract          Septo^-marginal 


Crossed 
idal 


Prepyramidal 
^tract  " 


Antero-lateral 
descending 
tract 


I  bundle 


Bundle  of 
Helweg 


Direct  pyramidal 
tract 


Fio.  403. — Tracts  of  descending  degeneration.    For  the  sake  of  clearness  each  is  shown  on  only  one 

side.    (After  Schafer.) 

Mingled  with  the  fibres  of  the  crossed  pyramidal  tract  are  a  few 
fibres  of  the  pyramid  which  have  not  crossed  in  the  medulla 
oblongata,  and  are  therefore  derived  from  the  same  side  of  the 
cerebrum  (uncrossed  lateral  pyramidal  fibres). 

The  pyramidal  fibres  are  not  found  at  all  in  vertebrates  below 
the  mammals.  In  the  lower  mammals  they  are  very  few,  and  in 
some  rodents  (rat,  mouse,  guinea-pig)  they  are  placed  in  the  posterior 
columns.  The  direct  pyramidal  tract  is  found  only  in  man  and 
the  higher  apes. 

Paralysis  resulting  from  section  of  the  pyramidal  tracts  is  not 
complete  and  persistent.  There  is,  therefore,  some  other  path  by 
which  volitional  impulses  arising  in  the  cortex  can  reach  the  motor 
cells  of  the  cord.  This  alternative  path  is  furnished  by  the  descend- 
ing fibres  of  the  anterior  column,  and  of  the  ventral  parts  of  the 
lateral  column,  especially  in  the  tract  next  to  be  described. 
Section  of  this  part  of  the  cord  produces  quite  as  complete  a 
paralysis  as  does  section  of  the  pyramidal  tracts.  In  vertebrates 
below  mammals  this  is  probably  the  only  path  between  the  higher 
brain  centres  and  the  lower  motor  centres  of  the  cord  (Schafer). 

(3.)  Antero-lateral  descending  tract,  or  tract  of  Loewenthal,  lies  by 
the  side  of  the  anterior  median  fissure,  and  extends  along  the  margin 
of  the  cord  towards  the  lateral  column.  These  fibres  originate  from 


CH.  XLV.]  DEGENERATION   TRACTS  657 

the  posterior  longitudinal  bundle  of  the  medulla  oblongata;  and  from 
other  sources  to  be  described  later.  They  end  by  synapses  in  the 
anterior  horn. 

(4.)  Tfie  prepyramidal  or  rubro-spinal  tract  (Monakow's  bundle). — 
This  is  situated  just  in  front  of  the  crossed  pyramidal  tract.  Its 
origin  is  in  the  cells  of  the  red  nucleus  in  the  mid-brain ;  hence  its 
name,  rubro-spinal.  Its  fibres  end  by  arborisations  in  the  grey  matter 
about  the  middle  of  the  crescent. 

(5.)  Bundle  of  Helweg. — The  exact  origin  and  destination  of  these 
fibres  are  not  known :  they  can  be  traced  from  the  neighbourhood  of 
the  olivary  body  in  the  medulla  oblongata,  and  pass  down  in  the 
anterior  part  of  the  lateral  column  in  the  cervical  region. 

(6.)  Short  tracts  in  the  posterior  column. — These  are  (a)  the  Comma 
tract ;  though  this  degenerates  downwards,  it  is  in  reality  a  sensory 
tract,  being  composed,  as  we  have  already  seen,  of  the  branches  of 
the  entering  posterior  root-fibres  which  pass  downwards  on  entering 
the  cord.  It  is  only  found  for  a  comparatively  short  distance  below 
the  actual  lesion,  (b)  Septo-marginal  fibres;  these  are  few  in 
number,  and  are  mainly  found  near  the  median  fissure,  where  they 
constitute  the  oval  bundle,  and  near  the  posterior  surface,  where  they 
form  the  median  triangle  bundle.  These  are  doubtless  short  associa- 
tion tracts,  and  are  mixed  with  others,  especially  in  the  ventral  part 
of  the  posterior  column,  which  have  an  "  ascending  "  course. 

Tracts  of  Ascending  Degeneration  (fig.  404). 

(1.)  Postero-median  column,  or  column  of  Goll. — This  consists  of 
fibres  derived  from  the  posterior  roots  of  the  sacral,  lumbar,  and  lower 


tract 


Direct  cerebellar 
tract 


Fia.  404.— Tracts  of  ascending  degeneration,  shown  on  one  side  of  the  cord  only.    (After  Schiifer.) 

thoracic  nerves.  These  fibres  enter  the  postero-lateral  column,  and 
gradually  pass  towards  the  mid-line,  as  already  explained.  They 
end  in  the  grey  matter  of  the  nucleus  gracilis  of  the  bulb. 

2  T 


658  STRUCTURE  OF  THE  SPINAL   CORD  [CH.  XLV. 

(2.)  Postero-lateral  column,  or  column  of  Burdach. — Many  of  the 
fibres  of  this  tract,  which  is  also  composed  of  the  entering  posterior 
nerve-roots,  pass  into  the  grey  matter  of  the  cord  either  immediately  on 
entrance,  or  in  their  course  upwards.  The  rest  continue  upwards  to  the 
medulla  oblongata,  but  those  from  the  lower  roots  pass  into  the  column 
of  G-oll,  as  just  stated ;  those  from  the  upper  roots  continue  to  travel 
upwards  in  the  column  of  Burdach,  and  end  in  the  grey  matter  of  the 
nucleus  cuneatus  in  the  medulla  oblongata. 

(3.)  Dorsal  or  direct  cerebellar  tract,  or  tract  of  Flechsig. — This  is 
found  in  the  cervical  and  thoracic  regions  of  the  cord,  and  is  situated 
between  the  crossed  pyramidal  tract  and  the  margin.  It  degenerates 
on  injury  or  section  of  the  cord  itself,  but  not  on  section  of  the 
posterior  nerve-roots.  In  other  words,  its  fibres  are  endogenous,  i.e., 
arise  from  cells  within  the  grey  matter  of  the  cord ;  these  cells  are 
those  of  Clarke's  eolumn  of  the  same  side ;  the  fibres  are  large  ones. 

(4.)  Ventral  cerelellar  or  antero-lateral  ascending  tract,  or  tract  of 
Growers. — This  is  situated  in  front  of  the  crossed  pyramidal  and  direct 
cerebellar  tracts  in  the  lumbar  region,  while  in  the  thoracic  and 
cervical  regions  it  forms  a  narrow  band  at  the  margin  of  the  cord, 
curving  round  even  into  the  anterior  column.  Its  fibres  intermingle 
with  those  of  the  antero-lateral  descending  tract.  They  originate 
from  the  lower  cells  of  Clarke's  column  of  the  same  side. 

Both  of  these  tracts,  as  their  names  indicate,  go  to  the  cerebellum, 
and  form  parts  of  one  and  the  same  system ;  they  connect  the  cells 
of  Clarke's  column  of  the  same  side  with  the  cerebellum.  In  the 
bulb,  the  system  divides ;  the  greater  number  of  fibres  pass  to  the 
vermis  by  the  inferior  cerebellar  peduncle,  while  a  smaller  number 
run  up  farther,  and  then  return  to  the  vermis  by  the  superior 
cerebellar  peduncle.  A  certain  number  of  fibres,  especially  the 
smaller  and  more  centrally  situated  ones,  end  in  grey  matter  in  the 
bulb,  pons,  and  mid-brain. 

(5.)  Tract  of  Lissauer,  or  posterior  marginal  zone. — This  is  a  small 
tract  of  ascending  fibres  situated  at  the  outer  side  of  the  tip  of  the 
posterior  horn.  These  are  fine  fibres  from  the  posterior  roots ;  they 
subsequently  pass  into  the  posterior  cornu. 

Association  fibres  in  the  Spinal  Cord. 

Some  of  the  short  tracts  already  alluded  to  as  demonstrable  in 
the  spinal  cord  are  bundles  of  association  fibres  which  connect 
its  different  levels  together.  The  main  difficulty  of  investi- 
gating them  by  the  degeneration  method  has  arisen  from  the 
fact  that  they  are  largely  intermingled  with,  and  so  are  hard  to 
distinguish  from,  the  long  tracts  which  connect  brain  and  cord 
together.  In  1853  Pfliiger  stated  that  reflex  irradiation  within  the 


CH.  XLV.]  SECTION   OF   THE   SPINAL   COKD  659 

spinal  cord  always  takes  place  in  an  upward  direction,  but  Sher- 
rington  in  his  work  found  many  exceptions  to  this  rule,  and  he 
sought  for  the  paths  which  are  capable  of  carrying  the  impulses 
down  the  cord  by  a  very  ingenious  method.  The  spinal  cord  of  a 
dog  was  completely  divided  across,  and  the  animal  was  kept  alive 
for  a  considerable  time  afterwards;  sufficient  time  was  allowed  to 
elapse  (roughly  about  a  year)  for  all  traces  of  the  degeneration  due 
to  this  lesion  to  have  disappeared.  The  cord  is  then  left,  as  it  were, 
like  a  cleaned  slate,  on  which  once  more  a  new  degeneration  can  be 
written  without  fear  of  confusion  with  a  previous  one.  The  second 
degeneration  produced  by  such  an  operation  as  hemisection  would 
then  affect  the  intra-spinal  fibres  only,  all  the  long  tracts  from  brain 
to  cord  having  been  wiped  out  by  the  first  operation.  The  complete 
topography  of  all  these  fibres,  which  are  very  numerous,  has  not  yet 
been  worked  out.  The  degenerated  fibres  are  scattered  throughout 
the  white  matter,  but  are  most  numerous  at  the  margins  of  the  cord. 
This  is  especially  true  for  the  longer  fibres,  and  some  of  them  appear 
to  be  very  long  indeed.  In  the  case  of  the  longer  fibres  there  is  no 
evidence  of  decussation;  in  the  case  of  the  shorter  fibres  there  is 
some  evidence  that  they  in  part  cross  to  the  other  side. 

Section  of  the  Spinal  Cord. 

Complete  transverse  section  of  the  spinal  cord  leads  to : — 

1.  Loss  of  motion  of  the  parts  supplied  by  the  nerves  below  the 
section  on  both  sides  of  the  body.     The  paralysis  is  not  confined  to 
the   voluntary   muscles,   but  includes   the  muscular   fibres   of  the 
blood-vessels  and  viscera.     Hence  there  is  fall   of  blood-pressure, 
paralysis  of  sphincters,  etc.,  immediately  after  the  operation,  but 
there  is  considerable  recovery  of  involuntary  muscles,  as  they  are 
supplied   by   autonomic   nerves ;    any   voluntary   control   over  the 
sphincters  is,  however,  permanently  lost. 

2.  Loss  of  sensation  in  the  same  regions. 

3.  Degeneration,  ascending  and  descending,  on  both  sides  of  the 
cord. 

Complete  transverse  section  of  the  spinal  cord  may  produce 
immediate  death  if  the  operation  is  performed  sufficiently  high  in 
the  cervical  region;  for  the  paralysed  muscles  will  then  include 
those  of  respiration.  The  spinal  cells  from  which  the  phrenic  and 
other  respiratory  nerves  originate  are  then  cut  off  from  the  respir- 
atory centre  in  the  bulb  above  them,  and  the  animal  will  die  of 
asphyxia.  One  sees  the  same  thing  after  severe  injury  to  the  upper 
cervical  cord  in  man,  as  when  he  "  breaks  his  neck." 

Hemisection. — If  the  operation  performed  is  not  a  complete  cut- 
ting of  the  spinal  cord  across  transversely,  but  a  cutting  of  half  the 
cord  across,  it  is  termed  hemisection,  or  semi-section.  This  loads  to : — 


660 


STRUCTURE   OF   THE   SPINAL   CORD 


[CH.  XLY. 


1.  Loss  of  motion  of  the  parts  supplied  by  the  nerves  below  the 
section  on  the  same  side  of  the  body  as  the  injury. 

2.  Loss  of  sensation  in  the  same  region.     The  loss  of  sensation  is 
not  a  very  prominent  symptom,  and  is  limited  to  the  sense  of  tactile 
discrimination  and  the  muscular  sense.     The  animal  can  still  feel 


FIG.  405. — The  above  diagrams  are  reproductions  of  photo-micrographs  from  the  spinal  cord  of  a  monkey, 
in  which  the  operation  of  left  hemisection  had  been  performed  some  weeks  previously  (Mott).  The 
sections  were  stained  by  Weigert's  method,  by  which  the  grey  matter  is  bleached,  while  the  healthy 
white  matter  remains  dark  blue.  The  degenerated  tracts  are  also  bleached.  A  is  a  section  of  the 
cord  in  the  thoracic  region  below  the  lesion ;  the  crossed  pyramidal  tract  is  degenerated.  B  is  a 
section  lower  down  in  the  lumbar  enlargement ;  the  degenerated  pyramidal  tract  is  now  smaller. 
C  is  a  section  in  the  thoracic  region  some  little  distance  above  the  lesion.  The  degenerated  tracts 
seen  are  in  the  outer  part  of  Goll's  column,  and  in  the  direct  cerebellar  tract.  D  is  a  section  higher 
up  in  the  cervical  region  ;  the  degeneration  in  Goll's  column  now  occupies  a  median  position  ;  the 
degenerations  in  the  direct  cerebellar  tract,  and  in  the  tract  of  Gowers,  are  also  well  shown.  Notice 
that  in  all  cases  the  degenerated  tracts  are  on  the  same  side  as  the  injury. 

sensations  of  pain  and  of  heat  and  cold.    This  is  more  fully  explained 
in  Chapter  XLIX. 

3.  Degeneration,  ascending  and  descending,  largely  confined  to 
the  same  side  of  the  cord  as  the  injury.  The  most  important  of 
these  are  shown  in  the  accompanying  diagrams  (fig.  405),  the  small 
text  beneath  which  should  be  carefully  studied. 


CHAPTEK  XLYI 

STRUCTURE   OF   THE   BULB,    PONS,    AND    MID-BRAIN 

WE  may  study  the  bulb  and  pons  by  examining  first  the  anterior 
or  ventral,  then  the  posterior  or  dorsal  aspect,  and  last  of  all  the 
interior. 

Anterior  Aspect. 

The  bulb  is  seen  to  be  shaped,  like  an  inverted  truncated 
cone,  larger  than  the  spinal  cord,  and  enlarging  as  it  goes  up  until 
it  terminates  in  the  still  larger  pons  (fig.  406,  p).  In  the  middle  line 
is  a  groove,  which  is  a  continuation  upwards  of  the  anterior  median 
fissure  of  the  spinal  cord;  the  columns  of  the  bulb  are,  speaking 
roughly,  continuations  upwards  of  those  of  the  cord,  but  there  is  a 
considerable  rearrangement  of  the  fibres  in  each.  Thus  the  prominent 
columns  in  the  middle  line,  called  the  pyramids  (a  a),  are  composed 
of  the  pyramidal  fibres,  which  in  the  spinal  cord  are  situated  princi- 
pally in  the  lateral  columns  of  the  opposite  side  (crossed  pyramidal 
tracts).  The  decussation  or  crossing  of  the  pyramids  (b)  occurs  at 
their  lower  part:  a  small  collection  of  the  pyramidal  fibres  is, 
however,  continued  down  the  cord  in  the  anterior  column  of  the  same 
side  of  the  cord  (direct  pyramidal  tract):  these  cross  at  different 
levels  lower  down  in  the  cord. 

On  the  outer  side  of  each  pyramid  is  an  oval  prominence  (c  c), 
which  is  not  represented  in  the  spinal  cord  at  all.  These  are  called 
the  olivary  bodies  or  olives ;  they  'consist  of  white  matter  outside, 
with  grey  and  white  matter  in  their  interior. 

The  restiform  bodies  at  the  sides  (d  d)  are  the  continuation  upwards 
of  those  fibres  from  cord  and  bulb  which  enter  the  cerebellum,  and 
the  upper  part  of  each  restiform  body  is  called  the  inferior  peduncle 
of  the  cerebellum. 

Posterior  Aspect. 

Fig.  407  shows  a  surface  view  of  the  back  of  the  bulb,  pons,  and 
mid-brain.  Again  we  recognise  some  of  the  parts  of  the  spinal  cord 

601 


662 


STRUCTURE  OF  THE  BULB,   PONS,   AND   MID-BRAIN         [CH.  XLYI. 


continued  upwards,  though  generally  with  new  names,  and  again  we 
see  certain  new  structures. 

The  posterior  median  fissure  is  continued  upwards,  and  on  each 
side  of  it  is  the  prolongation  upwards  of  the  posterior  column  of 


Fia.  406. — Ventral  or  anterior  surface  of 
the  pons  Varolii,  and  medulla  oblon- 
gata.  a,  a,  Pyramids ;  b,  their  decus- 
sation ;  c,  c,  olivary  bodies ;  d,  d, 
restiform  bodies ;  e,  arcuate  fibres ; 
/,  fibres  passing  from  the  anterior 
column  of  the  cord  to  the  cere- 
bellum ;  g,  anterior  column  of  the 
spinal  cord ;  h,  lateral  column ;  p, 
pons  Varolii ;  i,  its  upper  fibres ; 
5,  5,  roots  of  the  fifth  pair  of  nerves. 


FIG.  407. — Dorsal  or  posterior  surface 
of  the  pons  Varolii,  corpora  quad- 
rigemina,  and  medulla  oblongata. 
The  peduncles  of  the  cerebellum 
are  cut  short  at  the  sides,  a,  a,  The 
upper  pair  of  corpora  quadri- 
gemina ;  b,  b,  the  lower ;  /,  /,  supe- 
rior peduncles  of  the  cerebellum ; 

c,  eminence    connected     with     the 
nucleus   of   the   hypoglossal   nerve : 
e,    that    of    the    glosso-pharyngeal 
nerve;  i,  that  of  the  vagus  nerve; 

d,  d,  restiform  bodies ;  p,  p,  poste- 
rior columns;    v,  v,  groove  in    the 
middle     of    the     fourth     ventricle, 
ending  below  in  the  calamus  scrip- 
torius ;  7,  7,  roots  of  the  auditory 
nerves. 


the  cord.     The  column  of  G-oll  is  now  called  the  Funiculus  gracilis, 
and  the  column  of  Burdach  the  Funiculus  cuneatus. 

The  two  funiculi  graciles  lie  at  first  side  by  side,  but  soon 
diverge  and  form  the  two  lower  boundaries  of  a  diamond-shaped  space 
called  the  floor  of  the  fourth  ventricle;  this  is  made  of  grey  matter; 
the  central  canal  of  the  cord  gets  nearer  and  nearer  to  the  dorsal 
surface  of  the  bulb,  till  at  last  it  opens  out  on  the  back  of  the  bulb, 
and  its  surrounding  grey  matter  is  spread  out  to  form  the  floor  of 
the  fourth  ventricle.  The  two  upper  boundaries  of  the  diamond-shaped 
space  are  made  by  the  superior  peduncles  of  the  cerebellum,  which 
contain  fibres  going  up  through  the  mid-brain  to  the  cerebrum. 
The  middle  peduncles  of  the  cerebellum  are  made  up  of  fibres  running 
towards  each  cerebellar  hemisphere  from  the  opposite  side  of  the  pons. 


CH.  XLVI.]  THE   CRANIAL  NERVES  663 

Running  down  the  centre  of  the  floor  of  the  fourth  ventricle  is 
a  shallow  groove;  on  each  side  of  this  is  a  rounded  longitudinal 
eminence  called  the  eminentia  teres ;  running  across  the  middle  of 
the  floor  are  a  number  of  fibres  (the  striae  acousticce),  which  join  the 
auditory  nerve. 

In  the  upper  part  of  the  diagram,  the  mid-brain,  with  the  corpora 
quadrigemina  (a  a,  I  I),  is  shown.  Here  there  is  once  more  a  canal 
which  penetrates  the  substance  of  the  mid-brain,  and  is  called  the 
aqueduct  of  Sylvius,  or  the  iter  a  tertio  ad  quartum  ventriculum ;  it 
leads,  as  its  name  indicates,  from  the  third  to  the  fourth  ventricle. 

The  Internal  Structure  of  the  Bulb,  Pons,  and  Mid-Brain. 

The  structure  of  the  interior  of  these  parts  is  complex,  and  the 
complexity  arises  from  the  circumstance  that  here  we  have  to  deal 
not  only  with  parts  running  upwards  from  cord  to  brain,  or  down 
from  brain  to  cord,  but  also  with  a  considerable  amount  of  grey 
matter  in  which  some  of  the  white  tracts  terminate,  or  from  which 
new  tracts  issue.  The  most  important  stretch  of  grey  matter  is  that 
which  appears  on  the  floor  of  the  fourth  ventricle,  and  which  is 
continued  upwards  around  the  Sylvian  aqueduct,  and  downwards 
into  the  spinal  cord ;  here  are  situated  groups  of  nerve-cells,  which 
are  spoken  of  as  centres,  or  nuclei.  The  most  important  of  these  are 
those  which  are  connected  with  the  cranial  nerves.  There  are 
twelve  pairs  of  cranial  nerves,  and  of  these  the  last  ten  pairs  originate 
from  the  floor  of  the  fourth  ventricle  or  the  neighbouring  grey 
matter. 

The  following  is  a  list  of  the  cranial  nerves : — 

1.  Olfactory. — This  is  the  nerve  of  smell. 

2.  Optic. — This  is  the  nerve  of  sight. 

A    rr°°ijOCU\  These  three  nerves   supply   the  muscles   of   the 

4.  Trocklear  JT  !, 

6.  AUucens    J  e^ebaU' 

5.  Trigeminal. — This  is  the  great  sensory  nerve  of  the  face  and 
head.     Its  smaller  motor  division  supplies  the  muscles  of  mastication 
and  a  few  other  muscles  also. 

7.  Facial. — This  is  mainly  the  motor  nerve  of  the  face  muscles. 

8.  Auditory. — This  is  divided  into  two  parts,  one  of  which,  called 
the  cochlear  nerve,  is  the  true  nerve  of  hearing,  and  is  distributed  to 
the  cochlea  of  the  internal  ear ;  the  other  division,  called  the  vestibular 
nerve,  is  distributed  to  the  vestibule  and  semicircular  canals  of  the 
internal  ear. 

9.  Glosso-pharyngeal. — This  is  a  mixed  nerve ;.  its  motor  fibres  pass 
to  certain  of  the  pharyngeal  muscles ;  its  sensory  fibres  are  mainly 
concerned  in  the  sense  of  taste. 


664  STRUCTURE   OF   THE   BULB,    PONS,    AND    MID-BRAIN         [CH.  XL7L 

10.  Vagus  or  pneumogastric. — This  is  a  nerve  with  varied  efferent 
and    afferent    functions;    its    branches   pass    to    pharynx,   larynx, 
oesophagus,    stomach,    lungs,    heart,    intestines,    liver   and    spleen. 
These  functions  we  have  already  studied  in  connection  with  those 
organs. 

11.  Spinal  accessory. — The  internal  branch  of  this  nerve  blends 
with  the  vagus,  and  its  larger  external  division  supplies  the  trapezius 
and  the  sterno-mastoid  muscles. 

12.  Hypoglossal. — This  is  the  motor  nerve  to  the  tongue  muscles. 
A  mere  enumeration  of  the  nerves  connected  to  the  bulb  shows 

how  supremely  important  this  small  area  of  the  brain  is  for  carrying 
on  the  organic  functions  of  life.  It  contains  centres  which  regulate 
deglutition,  vomiting,  the  secretion  of  saliva,  etc.,  respiration,  the 
heart's  movements,  and  the  vaso-motor  nerves. 

When  we  further  consider  that  the  various  centres  are  connected 
by  groups  of  association  fibres,  we  at  once  realise  the  reason  for 
the  complexity  of  the  structures  where  all  this  busy  traffic  takes 
place. 

In  the  enumeration  of  the  cranial  nerves,  it  will  be  noticed  that 
many  of  them  are  either  wholly  motor  or  wholly  sensory,  and  that 
some  of  them,  like  the  spinal  nerves,  have  a  double  function.  The 
motor  nerve  fibres  start  as  axons  from  the  groups  of  nerve-cells  in 
the  grey  matter  of  this  region,  just  as  the  motor  fibres  in  the  spinal 
nerves  originate  from  the  cells  of  the  spinal  grey  matter.  There  is 
a  corresponding  resemblance  in  the  origin  of  the  sensory  fibres  of 
the  cranial  and  spinal  nerves.  In  the  latter,  it  will  be  remembered, 
they  originate  as  outgrowths  from  the  cells  of  the  spinal  ganglia,  one 
branch  growing  to  the  periphery,  and  the  other  to  the  spinal  cord, 
where  it  terminates  after  a  more  or  less  extended  course  by  forming 
synapses  with  the  cells  of  the  grey  matter.  In  the  sensory  cranial 
nerves  the  fibres  have  a  corresponding  origin  in  peripheral  ganglia, 
and  those  branches  which  grow  towards  the  bulb  terminate  by  arboris- 
ing around  special  groups  of  cells  spoken  of  as  the  sensory  nuclei. 

The  following  diagram  (fig.  408)  roughly  indicates  the  position 
of  these  nuclei ;  the  motor  nuclei  are  coloured  blue,  and  the  sensory 
red.  It  must,  however,  be  clearly  recognised  that  while  the  motor 
nuclei  are  true  centres  of  origin,  the  so-called  sensory  nuclei  are 
groups  of  cells  around  which  the  entering  sensory  fibres  arborise ;  these 
cells  do  not  give  origin  to  the  axons  of  the  sensory  nerves.  After  we 
have  studied  the  internal  structure  of  the  bulb  we  shall  be  able  to 
return  once  more  to  the  cranial  nerves,  in  order  that  we  consider  their 
origin  and  function  in  greater  detail. 

But  this  diagram  will  give  a  general  idea  of  the  positions  of  the 
nuclei.  "We  see  that  the  so-called  sensory  nuclei  (coloured  red) 
are  in  the  minority;  they  comprise  the  sensory  nucleus  of  the 


CH.  XLVI.] 


THE    CRANIAL   NERVES 


665 


fifth  nerve  with  its  long  descending  root,  the  nuclei  of  the  eighth 
nerve  (only  one  of  which,  VHIra.,  is  seen  in  the  diagram),  and  the 
glosso-pharyngeal  and  vagal  portions  of  a  long  strand  of  nerve-cells 


3rd.  Ventricle 


C.G. 


Str.  A 


Lateral  column 
Funiculus  cuneatus 
Funiculus  gracilis 


FIG.  408.— Diagram  to  show  the  position  of  the  nuclei  of  the  cranial  nerves  (after  Sherrington).  The 
medulla  and  pons  are  viewed  from  the  dorsal  aspect,  the  cerebrum  and  cerebellum  having  been  cut 
away.  The  nuclei  (sensory  coloured  red,  and  motor  blue)  are  represented  as  being  seen  through 
transparent  material.  C.Q.  a.t  anterior  corpus  quadrigeminum ;  C.Q.  p.,  posterior  corpus  quadri- 
geminum  ;  C.G.,  corpus  genieulatum  ;  v.v.,  value  of  Vieussens  ;  I.e.,  locus  cceruleus;  e.t.,  eminentia 
teres;  str.  A.,  stria?  acoustic*.  S.P.,  M.P.,  and  I.P.,  superior  middle  and  inferior  cerebellar 
peduncles  respectively  cut  through.  The  numerals  III.  to  XII.  indicate  the  nuclei  of  the  respec- 
tive cranial  nerves,  all  shown  on  the  left  side  except  the  accessory-vago-glosso-pharyngeal  IX.,  X.,  XI., 
which  to  avoid  confusion  is  placed  on  the  right  side.  Vm.  is  the  motor  nucleus  of  the  fifth  nerve  ; 
Vei.,  the  sensory  nucleus  of  the  same  nerve  with  its  long  descending  root;  VHIm.,  the  median 
nucleus  of  the  auditory  nerve;  N.I).  Nucleus  of  Deiters;  n.  amb.  nucleus  ambiguus.  The  position 
of  the  descending  root  of  the  ninth  and  tenth  (fasciculus  solitarius)  is  also  indicated  (J.  s.). 

called  the  combined  nucleus  of  the  ninth,  tenth,  and  eleventh  nerves. 
The  remaining  nuclei  (coloured  blue)  are  efferent,  and  may  be 
principally  arranged  into  two  groups : — (1)  the  nuclei  of  the  third, 


666 


STRUCTURE   OF  THE   BULB,   PONS,   AND   MID-BRAIN         [CH.  XLVI. 


fourth,  sixth,  and  twelfth  nerves,  which  are  close  to  the  middle  line ; 
and  (2)  the  motor  nucleus  of  the  fifth,  the  nucleus  of  the  seventh,  and 
the  nucleus  ambiguus  (motor  nucleus  of  the  ninth  and  tenth  nerves) 
which  form  a  line  more  lateral  in  position. 

It  should  be  added  that,  except  a  portion  of  the  optic  nerve  fibres, 
a  few  fibres  of  the  third,  and  the  whole  of  the  fourth  nerves,  none 
of  the  fibres  of  the  cranial  nerves  cross  to  the  opposite  side. 

The  first  two  pairs  of  cranial  nerves,  the  olfactory  and  the  optic, 
will  be  studied  in  connection  with  smell  and  vision  later  on. 


SUP.    PED.  OF    CEREBELLUM 
MIDDLE         ., 


CEREBELLAR 

4 
HEMISPHERE 


FIG.  409. — Diagrammatic  representation  of  dorsal  aspect  of  medulla,  pons,  and  mid-brain. 

We  can  now  pass  to  the  consideration  of  transverse  sections  of 
this  part  of  the  central  nervous  system.  We  will  limit  ourselves  to 
seven,  the  level  of  which  is  indicated  in  the  above  diagram  (fig.  409). 
The  cerebellum  has  been  bisected  into  two  halves  and  turned  out- 
wards, its  upper  peduncles  having  been  cut  through  to  render  the 
parts  more  evident.  The  position  of  our  seven  sections  is  indicated 
by  the  transverse  lines  numbered  1  to  7. 

First  section  (fig.  410). — This  is  taken  at  the  lowest  level  of  the 
bulb,  through  the  region  of  the  decussation  of  the  pyramids.  The 
similarity  to  the  cervical  cord  will  be  at  once  recognised;  the 


CH.  XLYI.] 


SECTIONS    OF   THE    BULB 


667 


passage  of  the  pyramidal  fibres  (P)  from  the  anterior  part  of  the 
bulb  to  the  crossed  pyramidal  tract  of  the  opposite  side  of  the  cord 
cuts  off  the  tip  of  anterior  horn  (A), 
which  in  sections  higher  up  appears  as 
an  isolated  mass  of  grey  matter,  called 
the  lateral  nucleus  (fig.  411,  nl).  The 
V  formed  by  the  two  posterior  horns 
is  opened  out,  and  thus  the  grey 
matter  with  the  central  canal  is  brought 
nearer  to  the  dorsal  aspect  of  the  bulb ; 
the  tip  of  the  cornu  swells  out  to 
form  the  substantia  gelatinosa  of  Ro- 
lando (E),  which  causes  a  prominence 
on  the  surface  called  the  tubercle  of 
Rolando ;  Gr  and  C  are  the  funiculi 
gracilis  and  cuneatus  respectively,  the 
continuations  upwards  of  the  columns 
of  Goll  and  Burdach. 

Many  of  the  fibres  of  the  pyramidal  tract 
terminate  in  the  mid-brain  and  pons,  hence 
this  tract  is  reduced  in  size  when  it  reaches 
the  bulb.  The  pyramidal  fibres  on  their  long 
journey  give  off  collaterals  to  the  cortex 
cerebri,  the  basal  ganglia  of  the  cerebrum, 
the  substantia  nigra  of  the  raid-brain,  the 
nuclei  pontis  of  the  pons,  and  lower  down  in 
the  cord  to  the  base  of  its  posterior  horn.  They,  however,  do  not  give  off  col- 
laterals to  the  motor  nuclei  of  the  cranial  nerves  on  their  passage  through  the  bulb 
(Schafer).  The  only  collaterals  given  off  in  this  region  are  a  few  to  the  olivary  nuclei. 

Second  section  (fig.  411). — This  is  taken  through  the  upper 
part  of  the  decussation.  Beginning  in  the  middle  line  at  the  top  of 
the  diagram,  we  see  first  the  posterior  median  fissure  (p.m/.),  below 
which  is  the  grey  matter  enclosing  the  central  canal  (c.c.),  and  con- 
taining the  nuclei  of  the  eleventh  and  twelfth  nerves ;  the  funiculus 
gracilis  (/.</.)  comes  next,  and  then  the  funiculus  cuneatus  (f.c.)  ;  these 
two  funiculi  have  now  grey  matter  in  their  interior:  these  masses 
of  grey  matter  are  called  respectively  nucleus  gracilis  (n.g.)  and 
nucleus  cuneatus  (n.c.) ;  the  fibres  which  have  ascended  the  posterior 
columns  of  the  cord  terminate  by  arborising  around  the  cells  of  this 
grey  matter ;  the  fibres  from  the  lower  part  of  the  body  end  in  the 
nucleus  gracilis,  and  those  from  the  upper  part  of  the  body  in  the 
nucleus  cuneatus.  These  nuclei  form  a  most  important  position  of 
relay  in  the  course  of  the  afferent  fibres  from  cord  to  brain.  The 
new  fibres  (the  second  relay  of  the  sensory  spinal  path)  arising  from 
the  cells  of  these  nuclei  pass  in  a  number  of  different  directions,  and 
break  up  the  rest  of  the  grey  matter  into  what  is  called  iheformatio 
reticularis  (f.r.) 


FIG.  410.— Section  through  the  bulb  at 
the  level  of  the  decussation  of  the 
pyramids.  G,  funiculus  gracilis,  con- 
tinuation of  column  of  Goll ;  C,  funiculus 
cuneatus,  continuation  of  column  of 
Burdach ;  R,  substantia  gelatinosa  of 
Rolando,  continuation  of  posterior  horn 
of  spinal  cord  ;  L,  continuation  of  lat- 
eral column'Of  cord  ;  A,  remains  of  part 
of  the  anterior  horn,  separated  from 
the  rest  of  the  grey  matter  by  the 
pyramidal  fibres  P,  which  are  crossing 
from  the  pyramid  of  the  medulla  to  the 
posterior  part  of  the  lateral  column  of 
the  opposite  side  of  the  cord. 

(After  L.  Clarke.) 


668 


STRUCTURE   OF   THE   BULB,    PONS,    AND    MID-BRAIN      [CH.  XLTI. 


The  nucleus  gracilis  and  nucleus  cuneatus  are  often  spoken  of  as 
the  posterior  column  nuclei ;  they  do  not  receive  all  the  ascending 
branches  of  the  posterior  root  fibres,  for  a  number  of  these  branches 
have  already  entered  the  grey  matter  and  arborised  amongst  its  cells 
in  the  spinal  cord  itself.  The  cells  of  the  posterior  column  nuclei 
are  of  moderate  size,  and  their  axons  pass  as  internal  arcuate  fibres 
into  the  reticular  formation  between  the  two  olivary  bodies,  which 
is  known  as  the  inter-olivary  layer.  They  cross  the  median  raphe 
dorsal  to  the  pyramids,  and  then  turn  upwards  towards  the  upper 


n.e 


n.c 


a.m.f. 


PIG.  411.— Transverse  section  of  the  medulla  oblongata  in  the  region  of  the  superior  decussation.  a.m./., 
Anterior  median  fissure ; /.a.,  superficial  arcuate  fibres;  py.,  pyramid;  n.a.r.,  nuclei  of  arcuate 
fibres; /.a1,  deep  arcuate  fibres  becoming  superficial;  o,  of,  lower  end  of  olivary  nucleus;  n.L, 
.  nucleus  lateralis;  f.r.,  fprmatio  reticularis;  /.o2,  arcuate  fibres  proceeding  from  the  formatio 
reticulans;  g,  substantia  gelatinosa  of  Rolando;  d.V.,  descending  root  of  fifth  nerve;  f.c., 
fumculus  cuneatus;  n.c.,  nucleus  cuneatus;  n.c.',  external  cuneate  nucleus;  n.g.,  nucleus 
gracihs ;  f.g.,  funiculus  gracilis;  p.m.f.,  posterior  median  fissure;  c.c.,  central  canal  surrounded 
Dy  grey  matter,  in  which  are  n.XL,  nucleus  of  the  eleventh  and  n.XIL,  nucleus  of  the  twelfth 
n«rve ;  s.d.,  superior  decussation  (decussation  of  fillet).  (Modified  from  Schwalbe.) 

parts  of  the  brain,  and  so  constitute  what  is  known  as  the  fillet.  In 
the  higher  parts  of  the  bulb  and  pons,  this  tract  is  reinforced  by 
fibres  from  the  cells  of  the  sensory  nuclei  of  the  cranial  nerves. 
The  fillet  becomes  a  longitudinal  bundle,  which  passes  upwards  to 
the  optic  thalamus,  which  forms  the  next  cell-station  on  the  path  of 
the  sensory  impulses  to  the  cortex. 

Other  points  to  be  noticed  in  the  section  are  the  substantia 
gelatinosa  of  Eolando  (g)  (representing  the  tip  of  the  posterior  cornu 
of  the  cord),  now  separated  from  the  surface  by  the  descending  root 
of  the  fifth  nerve  (d.  V.) ;  the  lateral  nucleus  (n.l.)  (remains  of  the 


CH.  XL VI.] 


SECTIONS    OF   THE   BULB 


669 


anterior  cornu  of  the  cord) ;  the  lower  part  of  the  grey  matter  of  the 
olivary  body  (o,  o'),  and  most  anteriorly  the  pyramid  (py). 

Third  section.— This  (fig.  412)  is  taken  at  about  the  middle  of 
the  olivary  body,  and  passes  also  through  the  lower  part  of  the  floor 
of  the  fourth  ventricle.  The  central  canal  has  now  opened  out  into 
the  fourth  ventricle,  and  the  grey  matter  on  its  floor  contains  the 
nuclei  of  the  twelfth  and  tenth  nerves ;  bundles  of  the  fibres  of  these 
nerves  course  through  the  substance  of  the  bulb,  leaving  it  at  the 
places  indicated  in  the  diagram. 


n.c 


FIG.  412.— Section  of  the  medulla  oblongata  at  about  the  middle  of  the  olivary  body,  f.l.a.,  Anterior 
median  fissure;  n.ar.,  nucleus  arcuatus;  p,  pyramid;  XII.,  bundle  of  hypoglossal  nerve  emerging 
from  the  surface;  at  b,  it  is  seen  coursing  between  the  pyramid  and  the  olivary  nucleus,  o;  f.a.e., 
external  arcuate  fibres ;  n.L,  nucleus  lateralis ;  a.,  arcuate  fibres  passing  towards  restiform  body, 
partly  through  the  substantia  gelatinosa,  g,,  partly  superficial  to  the  descending  root  of  the  fifth 
nerve,  d.V. ;  X.,  bundle  of  vagus  root  emerging;  f.r.,  formatio  reticularis ;  C.r.,  corpus  restiforme, 
beginning  to  be  formed,  chiefly  by  arcuate  fibres,  superficial  and  deep ;  n.c.,  nucleus  cuneatus ;  n.g., 
nucleus  gracilis;  <,  attachment  of  the  ligula;  /.s.,  funiculus  solitarius;  n.X.,  n.X.',  two  parts  of 
the  vagus  nucleus;  n.XII.,  hypoglossal  nucleus;  «.£.,  nucleus  of  the  funiculus  teres;  n.am., 
nucleus  ambiguus;  r.,  raphe;  A.,  continuation  of  the  anterior  column  of  cord;  o',  o",  accessory 
olivary  nucleus;  p.o.l.,  pedunculus  olivse.  (Modified  from  Schwalbe.) 

The  nucleus  gracilis  and  nucleus  cuneatus  are  pushed  into  a  more 
lateral  position,  and  higher  up  are  replaced  by  small  masses  of  grey 
matter  mingled  with  nerve-fibres  (nucleus  posterior) ;  the  restiform 
body  (C.r.)  now  forms  a  well-marked  prominence,  and  the  olivary 
body  is  well  seen  with  its  dentate  nucleus ;  from  the  open  mouth  of 
this  corrugated  layer  of  grey  matter  a  large  number  of  fibres  issue, 
and  passing  through  the  raphe,  course  as  internal  arcuate  fibres  to 
the  opposite  restiform  body,  and  thus  to  the  cerebellum ;  some  pass 
to  the  restiform  body  of  the  same  side;  the  continuation  of  the 


670 


STRUCTURE  OF  THE   BULB,   PONS,   AND   MID-BRAIN      [CH.  XLVL 


direct  cerebellar  tract  of  the  cord  also  passes  into  the  restiform  body. 
Its  fibres  terminate  by  arborisations  round  Purkinje's  cells  in  the 
vermis  of  the  cerebellum.  The  continuation  of  the  tract  of  Gowers 
lies  just  dorsal  to  the  olivary  body.  The  funiculus  solitarius  and 
nucleus  ambiguus,  also  seen  in  this  section,  will  be  considered  in 
our  account  of  the  origin  of  the  ninth  and  tenth  cranial  nerves. 

Fourth  section  (fig.  413). — This  is  taken  through  the  middle  of 
the  pons,  and  shows  much  the  same  kind  of  arrangement  as  in  the 
upper  part  of  the  bulb.  The  general  appearance  of  the  section  is, 
however,  modified  by  a  number  of  transversely  coursing  bundles  of 


FIG.  413.— Section  across  the  pons,  about  the  middle  of  the  fourth  ventricle,  py,  Pyramidal  bundles  ; 
po.,  transverse  fibres  passing  pol  behind,  andpo2,  in  front  of  py;  r.,  raphe  ;  o.s.,  superior  olive; 
a.V.,  bundles  of  motor  root  of  V.  nerve  enclosed  in  a  prolongation  of  the  substance  of  Rolando;  t, 
trapezium ;  VI.,  the  sixth  nerve,  n.VL,  its  nucleus  ;  VII.,  facial  nerve;  Vll.a.,  intermediate  por- 
tion, n.VIL,  its  nucleus;  VIII.,  auditory  nerve ;  n.VIIL,  Deiters'  nucleus,  formerly  called  the 
lateral  nucleus  of  the  auditory.  (After  Quain.) 

fibres,  most  of  which  are  passing  to  the  cerebellar  hemispheres  and 
form  the  middle  cerebellar  peduncles.  Intermingled  with  these  is  a 
considerable  amount  of  grey  matter  (nuclei  pontis). 

From  the  cells  of  the  nuclei  pontis,  the  fibres  of  the  middle 
peduncle  take  origin,  and  many  fibres  and  collaterals  of  the  pyramidal 
tract  arborise  around  them.  The  continuation  of  the  pyramids  (py)  is 
imbedded  between  these  transverse  bundles.  The  pyramidal  fibres 
which  terminate  in  the  pons  are  situated  postero-laterally,  and  are 
spoken  of  as  cortico-pontine  in  contradistinction  with  those  of  the 
pyramidal  tract  proper  (cortico-spinal)  which  pass  down  through  the 
bulb  to  the  cord. 

The  pyramidal  bundles  are  separated  from  the  reticular  formation 


CH.  XLVI.]  SECTIONS   OF  PONS   AND   MID-BRAIN  671 

by  deeper  transverse  fibres,  which  constitute  what  is  known  as  the 
trapezium  (f).  These  fibres  belong  to  a  different  system,  and  form 
part  of  the  central  auditory  path ;  some  of  them  connect  the  auditory 
nuclei  of  the  two  sides  together.  The  larger  olivary  nucleus  is  no 
longer  seen,  but  one  or  two  small  collections  of  grey  matter  (o.s.)  repre- 
sent it  and  constitute  the  superior  olivary  nucleus.  These  as  well  as  a 
collection  of  nerve-cells  in  the  trapezium  (nucleus  of  the  trapezium) 
are  connected  with  fibres  of  the  trapezium,  while  some  of  their  axons 
pass  into  the  adjacent  lateral  part  of  the  fillet. 

The  nucleus  of  Deiters  (n.  VII L,  fig.  413)  begins  to  appear  in  the 
upper  part  of  the  bulb,  and  extends  into  the  pons ;  it  lies  near  the 
floor  of  the  ventricle,  a  little  mesial  to  the  restiform  body.  The 
nerve-fibres  connected  with  its  cells  pass  towards  the  middle  line, 
and  enter  the  posterior  longitudinal  bundle,  which  is  more  clearly  seen 
in  the  two  next  sections  (fig.  414).  This  bundle  of  fibres  connects 
Deiter's  nucleus,  the  nucleus  of  the  third  and  sixth  nerves,  and  the 
anterior  horn  cells  of  the  spinal  cord.  The  fibres  which  pass  into  it 
from  Deiters'  nucleus  bifurcate,  one  branch  passing  upwards  to 
arborise  around  the  cells  mainly  of  the  oculo-motor  nucleus  of  the 
opposite  side ;  the  other  extends  downwards  through  the  bulb  into 
the  cord,  where  they  are  found  in  the  antero-lateral  descending  tract 
of  each  side.  They  end  by  synapses  around  the  anterior  horn  cells. 

This  bundle  receives  in  addition  to  the  fibres  from  Deiters'  nucleus,  other  fibres 
from  the  sensory  nucleus  of  the  fifth  nerve,  and  from  large  cells  in  the  reticular  for- 
mation of  mid-brain,  pons,  and  bulb. 

The  nerves  which  are  connected  with  the  grey  matter  of  this 
region  of  the  pons  are  the  sixth,  seventh,  and  eighth,  as  shown  in  the 
diagram.  The  nuclei  in  connection  with  the  fifth  nerve  are  higher 
up,  where  the  floor  of  the  ventricle  is  again  narrowing.  At  last,  in 
the  region  of  the  mid-brain,  we  once  more  get  a  canal  (Sylvian 
aqueduct)  which  corresponds  to  the  central  canal  of  the  spinal  cord. 

Fifth  and  Sixth  sections  are  taken  through  the  mid-brain,  and 
are  drawn  on  a  smaller  scale  than  the  others  we  have  been  examin- 
ing ;  they  represent  the  actual  size  of  the  sections  obtained  from  the 
human  subject. 

Near  the  middle  is  the  Sylvian  aqueduct,  with  its  lining  of  ciliated 
epithelium.  In  the  grey  matter  which  surrounds  it  are  large  nerve- 
cells  from  which  the  fourth  nerve,  and  higher  up  the  third  nerve, 
originate ;  the  fibres  of  the  third  nerve  are  seen  issuing  from  these  in 
fig.  414,  R,  III.  The  reticular  formation  of  the  pons  is  continued  up 
into  the  mid-brain,  and  is  called  the  tegmentum.  It  is  composed  of 
both  longitudinal  and  transverse  bundles  of  fibres  intermingled  with 
grey  matter.  Its  transverse  fibres  include  those  of  the  superior 
peduncles  of  the  cerebellum  which  decussate  in  the  middle  line  (fig. 
414,  A,  S.C.P.). 


672  STRUCTURE   OF   THE   BULB,    PONS,    AND    MID-BRAIN       [CH.  XLVI 

Another  important  longitudinal  bundle  in  the  tegmentum  is  the 
fillet.  This,  we  have  seen,  is  the  longitudinal  continuation  of  the 
internal  arcuate  fibres,  which,  starting  from  the  cells  of  the  posterior 
column  nuclei  of  the  opposite  side,  form  the  second  relay  on  the 
sensory  path ;  to  these  fibres  others  are  added  which  originate  from 


C.Q.  /  c.o. 


FIG.  414.— Outline  of  two  sections  across  the  mid-brain :  A,  through  the  middle  of  the  inferior ;  B, 
through  the  middle  of  the  superior  corpora  quadrigemina,  C.Q.  Cr.,  crusta;  S.N.,  substantia  nigra 
— shown  only  on  one  side ;  T,  tegmentum ;  S,  Sylvian  aqueduct,  with  its  surrounding  grey  matter ; 
L.G.,  lateral  groove;  p.l.,  posterior  longitudinal  bundle  ;  d.  V.,  descending  root  of  the  fifth  nerve  ; 
S.C.P.,  superior  cerebellar  peduncle ;  F,  fillet ;  III.,  third  nerve.  The  dotted  circle  in  B  represents 
the  situation  of  the  tegmental  nucleus.  In  B  the  three  divisions  of  the  crusta  are  indicated  on  one 
side.  The  pyramidal  fibres  (Pi/)  are  in  the  middle,  and  the  fronto-cerebellar  (F.C.)  and  temporo- 
occipital  cerebellar  (T.O.C.)  at  the  sides.  (After  Schafer.) 

other  masses  of  grey  matter  in  bulb  and  pons.  In  the  mid-brain  the 
fillet  splits  into  three  bundles,  termed  the  lateral,  the  upper,  and  the 
mesial  fillet. 

(1)  The  lateral  fillet  is  chiefly  formed  by  fibres  derived  from  the  accessory  audi- 
tory, the  inferior  olivary,  and  trapezoid  nuclei  of  the  opposite  side.     Some  of  its 
fibres  terminate  by  synapses  around  a  new  collection  of  cells  (the  lateral  fillet 
nucleus) ;  their  axons  pass  inwards  towards  the  raphe.     The  rest  of  its  fibres  can  be 
traced  to  the  grey  matter  of  the  inferior  corpora  quadrigemina. 

(2)  The  upper  fillet  consists  of  fibres  which  go  to  the  superior  corpora  quadri- 
gemina and  partly  to  the  tegmental  region  of  the  mid-brain  and  optic  thalamus. 

(3)  The  mesial  fillet  goes  on  through  the  tegmentum  of  the  crus  cerebri,  and  its 
fibres  terminate  around  the  cells  of  the  optic  thalamus,  and  the  subthalamic  region. 
From  here  fresh  axons  forming  a  new  relay  continue  the  afferent  impulses  to  the 
cortex  of  the  cerebrum. 

The  mesial  fillet  is  the  important  link  in  this  region  between 
the  sensory  spinal  nerves  and  the  part  of  the  brain  which  is  the  seat 
of  those  processes  we  call  sensations.  But  most  of  the  fibres  which 
continue  the  sensory  path  of  the  cranial  nerves  form  another  less 
well-defined  tract  (the  central  tract  of  the  sensory  cranial  nerves)  which 
lies  dorsal  to  the  fillet,  but  terminates  like  it  in  the  subthalamic 
region  and  optic  thalamus,  whence  a  new  relay  carries  on  the 
impulses  to  the  cortex. 

Ventral  to  the  tegmentum  is  a  layer  of  grey  matter,  of  which 
the  cells  are  deeply  pigmented ;  hence  it  is  called  the  substantia 
nigra  (S.N.).  This  receives  many  collaterals  from  the  pyramidal 
bundles. 

The  white  matter  on  the  ventral  side  of  this  is  known  as  the 


CH.  XLVI.]        ORIGINS   AND    FUNCTIONS    OF   CRANIAL  NERVES  673 

crusta  (Or)  orpes.  It  is  here  that  the  pyramidal  bundles  are  situated ; 
these  occupy  its  middle  three-fifths  (Py).  The  mesial  fifth  is  occupied 
by  fibres  passing  from  the  frontal  region  of  the  cerebrum  to  the  pons, 
and  thence  to  the  cerebellum ;  hence  they  are  called  fronto-cerebellar 
fibres.  The  fibres  occupying  the  lateral  fifth  are  usually  spoken  of 
as  temporo-occipital  cerebellar  fibres,  but  there  is  no  certainty  as  yet 
regarding  their  origin  or  functions. 

The  corpora  quadrigemina  are  formed  mainly  of  grey  matter; 
from  each  superior  corpus  a  bundle  of  white  fibres  passes  upwards 
and  forwards  to  the  geniculate  bodies,  eventually  joining  the  optic 
tract  of  the  same  side.  The  white  layer  on  the  surface  of  the  grey 
matter  of  the  C.  quadrigemina  is  derived  from  the  optic  tract;  these 
fibres  come  from  the  retina,  and  terminate  by  arborising  around  the 
cells  of  the  grey  matter  of  the  C.  quadrigemina. 

The  cells  of  the  grey  matter  of  the  corpora  quadrigemina  differ 
greatly  in  form  and  size ;  the  destination  of  their  axons  is  not  pre- 
cisely known,  but  some  pass  ventralwards,  cross  at  the  raphe,  and 
constitute  the  fountain  decussation  of  Meynert ;  after  decussation 
they  form  the  main  mass  of  the  ventral  longi- 
tudinal bundle ;  this  gives  off  collaterals  to  the 
nuclei  of  the  three  nerves  that  supply  the  eye 
muscles,  and  then  runs  ventro-laterally  to  the 
posterior  longitudinal  bundle,  with  which  its 
fibres  ultimately  mix  in  the  antero-lateral 
descending  tract  of  the  spinal  cord.  Fio  415._Sect^through 

Seventh    section. — This    is    through    the       cms   of  cerebrum,    cr, 

T,     •  j  e  .1       /     !_•    i_  j.    •  crusta ;     S.N..    substantia 

CrUS.       It    IS  made  lip  Of  CrUSta    (which  Contains          nigra;  T,  tegmentum. 

the  motor  fibres),  tegmentum  (which  contains 

the  sensory  fibres,  especially  the  bundle  called  the  mesial  fillet),  and 

the  substantia  nigra,  the  grey  matter  which  separates  them. 

Origins  and  Functions  of  the  Cranial  Nerves. 

Having  now  studied  the  internal  construction  of  these  parts,  we 
can  take  up  more  fully  the  origins  and  functions  of  the  cranial  nerves 
which  originate  there.  The  olfactory  nerve  is  connected  to  the 
cerebrum,  and  will  be  considered  with  the  sense  of  smell.  The 
optic  nerve  will  be  studied  with  vision,  though  it  is,  as  we  have  seen, 
immediately  connected  with  the  mid-brain. 

The  third,  fourth,  and  sixth  nerves  supply  the  muscles  of  the  eye. 
Gaskell  discovered  among  the  rootlets  of  the  third  and  fourth  nerves 
the  vestiges  of  a  degenerated  and  functionless  ganglion,  which  indicates 
the  previous  existence  of  a  separate  sensory  root.  Sherrington  has 
shown  that  in  these  three  nerves  sensory  fibres  are  present  which  are 
connected  to  the  sensorial  nerve  endings  (muscle- spindles). 

The  third  nerve  (motor  oculi)  arises  in  a  group  of  nerve-cells  in 

2  U 


674  STRUCTURE   OF   THE   BULB,   PONS,   AND   MID-BRAIN       [CH.  XLYI. 

the  grey  matter  on  the  side  of  the  Sylvian  aqueduct  underneath  the 
superior  corpus  quadrigeminum,  and  close  to  the  middle  line.  The 
anterior  part  of  this  nucleus  is  composed  of  small  cells  from  which 
small  nerve-fibres  originate  for  the  ciliary  muscle  and  sphincter  of 
the  iris  (intrinsic  muscles  of  the  eyeball).  These  fibres  correspond 
to  the  visceral  fibres  of  a  spinal  nerve,  and,  like  them,  have  a  cell 
station,  namely,  in  the  ciliary  ganglion.  The  posterior  part  of  the 
nucleus  is  composed  of  larger  cells,  and  these  give  rise  to  larger 
fibres  which  supply  the  following  extrinsic  eye-muscles: — superior 
rectus,  inferior  rectus,  internal  rectus,  inferior  oblique  and  levator 
palpebrse. 

The  fourth  nerve  (trochlear)  takes  origin  from  the  grey  matter 
immediately  below  the  centre  of  the  third,  but  slightly  more  lateral 
in  position.  It  is  underneath  the  inferior  corpus  quadrigeminum. 
It  supplies  the  superior  oblique  muscle  of  the  opposite  eyeball. 

The  sixth  nerve  (abducens)  arises  from  a  centre  beneath  the 
eminentia  teres  in  the  upper  part  of  the  floor  of  the  fourth  ventricle 
near  the  middle  line.  It  supplies  the  external  rectus. 

It  is  obviously  necessary  that  the  eye-muscles  should  work 
together  harmoniously,  that  the  two  eyeballs  should  also  be  moved 
simultaneously  and  in  corresponding  directions,  and  that  such  move- 
ments should  take  place  in  accordance  with  the  necessities  of  vision. 
This  is  provided  for  in  the  shape  of  association  fibres  which  link  the 
centres  of  the  eye-muscles  together.  The  principal  association  tracts 
are  the  posterior  longitudinal  bundle,  which  connects  the  nuclei  of 
the  third  and  sixth  nerves,  and  the  ventral  longitudinal  bundle 
which  unites  the  optic  nerves  through  the  intermediation  of  the  cells 
of  the  C.  quadrigemina,  with  the  nuclei  of  all  these  nerves.  It  should 
also  be  remembered  that  all  the  fibres  of  the  fourth,  and  some  of 
those  of  the  third  nerve,  decussate  in  the  middle  line. 

The  fifth  nerve  (trigeminal)  is  a  mixed  nerve  ;  it  leaves  the  side  of 
the  pons  in  a  smaller  motor,  and  a  larger  sensory  division.  The 
former  supplies  the  muscles  of  mastication,  the  tensors  of  the  palate 
and  tympanum,  the  mylo-hyoid,  and  the  anterior  belly  of  the 
digastric;  the  sensory  division  has  upon  it  a  ganglion  called  the 
Gasserian  ganglion;  it  is  the  great  sensory  nerve  of  the  face  and 
head.  The  motor  fibres  arise  from  the  motor  nucleus  (Vra,  fig.  408), 
which  lies  at  the  lateral  edge  of  the  upper  part  of  the  floor  of  the 
fourth  ventricle,  but  a  certain  number  of  its  fibres  arise  from  cells 
in  the  lower  part  of  the  mid-brain  and  upper  part  of  the  pons; 
this  long  stretch  of  nerve-cells,  indicated  by  the  long  blue  tail  in  the 
diagram,  is  called  the  accessory  or  superior  motor  nucleus  of  the  fifth. 
The  sensory  fibres  arise  from  the  cells  of  the  Gasserian  ganglion, 
which  resemble  in  structure  those  of  a  spinal  ganglion ;  one  branch 
of  each  passes  to  the  periphery  in  the  skin  of  the  head  and  face,  and 


CH.  XLVI.]  THE  SEVENTH  NERVE  675 

the  other  grows  central  wards ;  on  reaching  the  pons  these  bifurcate, 
the  ascending  branches  arborise  around  the  principal  sensory  nucleus 
of  the  fifth  (yd,  fig.  408),  which  lies  just  lateral  to  the  motor  nucleus, 
while  the  descending  branches  pass  down  into  the  bulb,  where  they 
form  the  descending  root  of  the  fifth,  and  some  reach  as  far  down 
in  the  spinal  cord  as  the  second  cervical  nerve.  Mingled  with  these 
descending  fibres  are  numerous  nerve-cells,  many  of  which  are  grouped 
in  clusters  (islands  of  Calleja),  and  the  descending  fibres  form  synapses 
around  them.  The  new  axons  arising  from  the  cells  of  the  sensory 
nuclei  pass  upwards  in  three  principal  tracts: — (1)  The  greater 
number  cross  the  raphe  and  join  the  mesial  fillet ;  (2)  some  ascend 
the  fillet  of  the  same  side ;  and  (3)  others  pass  into  a  special  ascending 
bundle  which  lies  near  the  ventricular  floor  (the  central  tract  of  the 
cranial  sensory  nerves). 

The  seventh  nerve  (facial)  is  the  great  motor  nerve  of  the  face 
muscles.  It  also  supplies  the  platysma,  the  stapedius,  stylo-hyoid, 
and  posterior  belly  of  the  digastric.  When  it  is  paralysed,  the 
muscles  of  the  face  being  all  powerless,  the  countenance  acquires  on 
the  paralysed  side  a  characteristic,  vacant  look,  from  the  absence  of  all 
expression :  the  angle  of  the  mouth  is  lower,  and  the  paralysed  half 
of  the  mouth  looks  longer  than  that  on  the  other  side ;  the  eye  has 
an  unmeaning  stare,  owing  to  the  paralysis  of  the  orbicularis  palpe- 
brarum.  All  these  peculiarities  are  exaggerated  when  at  any  time 
the  muscles  of  the  opposite  side  of  the  face  are  made  active  in  any 
expression,  or  in  any  of  their  ordinary  functions.  In  an  attempt  to 
blow  or  whistle,  one  side  of  the  mouth  and  cheeks  acts  properly,  but 
the  other  side  is  motionless,  or  flaps  loosely  at  the  impulse  of  the 
expired ,  air ;  in  trying  to  suck,  one  side  only  of  the  mouth  acts ; 
in  feeding,  on  account  of  paralysis  of  the  buccinator  muscle,  food 
lodges  between  the  cheek  and  gums. 

The  motor  fibres  originate  from  a  nucleus  in  the  ventricular  floor 
below  that  of  the  fifth  and  to  the  outer  side  of  that  of  the  sixth 
nerve.  As  they  curve  over  the  nucleus  of  the  sixth,  they  give  off  a 
bundle  of  fine  fibres  which  cross  the  raphe,  but  their  destination  is 
unknown.  The  facial  nucleus  receives  collaterals  from  the  sensory 
tracts  in  the  reticular  formation. 

The  seventh  nerve,  however,  is  not  wholly  motor.  The  geniculate 
ganglion  on  it  is  of  spinal  type ;  the  fibres  which  arise  from  it  pass 
centrally  into  the  pars  intermedia  of  Wrisberg,  which  enters  the  pons 
between  the  seventh  and  eighth  nerves ;  these,  like  other  sensory  fibres, 
divide  into  ascending  and  descending  branches ;  the  latter  have  been 
traced  down  to  the  sensory  nucleus  of  the  glosso-pharyngeal  nerve. 
The  peripheral  branches  of  the  geniculate  ganglion  cells  pass  into  the 
large  superficial  petrosal  and  chorda  tympani,  the  gustatory  fibres  of 
which  they  probably  furnish.  The  secretory  fibres  of  the  chorda 


676 


STRUCTURE   OF   THE    BULB,    PONS,    AND    MID-BRAIN        [CH.  XLVI. 


tympani  are  efferent  fibres  which  reach  it  from  the  facial  nucleus 
via  the  pars  intermedia. 

The  eighth  nerve  (auditory)  runs  into  the  hinder  margin  of  the 
pons  by  two  roots.  One  winds  round  the  restiform  body  dorsal  to 
it,  and  is  known  as  the  dorsal  or  cochlear  division ;  the  other  passes 
ventro-mesially  on  the  other  side  of  the  restiform  body,  and  is  known 
as  the  ventral  or  vestibular  division. 

We  will  take  these  two  parts  separately.  The  fibres  of  the 
cochlear  nerve  take  origin  from  the  bipolar  nerve-cells  of  the  spiral 
ganglion  of  the  cochlea;  the  peripheral  axons  ramify  among  the 
hair  cells  of  the  organ  of  Corti,  and  the  central  axons  pass  towards 
the  pons ;  as  they  enter  they  bifurcate,  and  some  pass  to  and  arborise 


tub. 


FIBRES  TO  NUCL.LEMNISCI 
&CORPORA  QUADR1GEMINA 


\S.O. 


NERVE-ENDINGS 

IN  ORGAN  OF  CORTl 

FIG.  416. — Cochlear  division  of  the  auditory  nerve,  r,  Restiform  body ;  K,  descending  root  of  „ the  fifth 
nerve;  tub.ac.,  acoustic  tubercle;  n.acc.,  accessory  nucleus;  s.o.,  superior  olive;  n.tr.,  trapezoid 
nucleus ;  n.VI.,  nucleus  of  the  sixth  nerve ;  VI.,  issuing  fibre  of  sixth  nerve.  (Schafer.) 

around  a  collection  of  nerve-cells  situated  between  the  two  roots  and 
the  restiform  body,  called  the  accessory  auditory  nucleus  ;  the  remain- 
ing fibres  terminate  similarly  in  a  collection  of  cells  in  the  grey  matter 
overlying  the  restiform  body,  and  extending  into  the  ventricular 
floor  in  its  widest  part.  This  is  called  the  ganglion  of  the  root,  and 
the  mass  of  grey  matter  is  termed  the  acoustic  tubercle.  The  auditory 
path  is  continued  by  new  axons  that  arise  from  these  cells.  Those 
from  the  accessory  nucleus  enter  the  trapezium,  and  pass  in  it  partly 
to  the  superior  olive  and  trapezoid  nucleus  of  the  same  side,  but 
mainly  to  the  corresponding  nuclei  of  the  opposite  side ;  some  fibres 
end  here,  others  traverse  the  nuclei,  and  merely  give  off  collaterals  to 
them ;  they  then  turn  upwards  in  the  lateral  fillet,  and  so  reach  the 
inferior  C.  quadrigemina.  The  fibres  which  arise  in  the  acoustic 


CH.  XLVI.] 


THE   EIGHTH   NERVE 


677 


tubercle  pass  superficially  over  the  floor  of  the  ventricle,  forming  the 
stria  acoustics;  having  crossed  the  raphe,  they  join  the  fibres  from  the 
accessory  nucleus  in  their  course  to  the  superior  olive  and  fillet. 
Here  again,  however,  a  few  fibres  pass  to  the  fillet  of  the  same  side. 

The  vestibular  nerve  arises  from  the  bipolar  cells  of  the  ganglion 
of  Scarpa,  which  is  situated  in  the  internal  auditory  meatus.  The 
peripheral  axons  ramify  among  the  hair  cells  of  the  epithelium  in  the 
utricle,  saccule,  and  semi-circular  canals.  The  central  axons  enter  a 
collection  of  small  nerve- cells  between  the  restiform  body  and  the 
descending  root  of  the  fifth ;  this  is  termed  the  principal  nucleus  ;  here 


TO  VERMIS 


TO  HEMISPHERE 


FIBRES    OF 
VESTIBULAR 
ROOT 


NERVE 
ENDINGS 
IN  MACUL/E 
&AMPULL/E 


FIG,  417.— Vestibular  division  of  the  auditory  nerve,  r,  Restiform  body ;  V,  descending  root  of  the  fifth 
nerve ;  d,  libres  of  descending  vestibular  root ;  n.d.,  cell  of  descending  vestibularnucleus  ;  D,  nucleus 
of  Deiters  ;  B,  nucleus  of  Bechterew;  n.t.,  nucleus  tecti  of  cerebellum  :  p.l.b.,  posterior  longitudinal 
bundle.  (Schiifer.) 

they  bifurcate ;  the  descending  branches  run  towards  the  lower  part  of 
the  bulb,  and  arborise  around  the  cells  of  the  neighbouring  grey  matter 
(descending  vestibular  nucleus).  The  ascending  branches  pass  upwards 
in  the  restiform  body  to  the  cerebellum,  in  their  course  giving  off  many 
collaterals  which  form  synapses  with  the  large  cells  of  two  nuclei 
near  the  outer  angle  of  the  ventricular  floor,  and  known  as  the 
nucleus  of  Deiters  and  nucleus  of  Bechterew  respectively.  The  fibres 
which  arise  from  Deiters'  nucleus  pass  into  the  posterior  longitudinal 
bundles  of  both  sides  (see  p.  674) ;  those  which  start  in  Bechterew 's 
nucleus  become  longitudinal,  but  their  destination  is  uncertain. 

The  accompanying  diagrams  (figs.  416  and  417)  will  serve  to  render 
these  complex  relationships  clearer. 


678  STRUCTURE  OF  THE   BULB,   PONS,   AND   MID-BRAIN        [CH.  XLYI. 

The  ninth  nerve  (glosso-pharyngeal)  gives  filaments  through  its 
tympanic  branch  (Jacobsen's  nerve)  to  parts  of  the  middle  ear; 
also,  to  the  carotid  plexus,  and  through  the  great  superficial  petrosal 
nerve  to  the  spheno-palatine  (Meckel's)  ganglion.  After  communi- 
cating, either  within  or  without  the  cranium,  with  the  vagus,  it  leaves 
the  cranium,  divides  into  the  two  principal  divisions  indicated  by 
its  name,  and  supplies  the  mucous  membrane  of  the  posterior  and 
lateral  walls  of  the  upper  part  of  the  pharynx,  the  Eustachian  tube, 
the  arches  of  the  palate,  the  tonsils  and  their  mucous  membrane, 
and  the  tongue  as  far  forwards  as  the  foramen  caecum  in  the  middle 
line,  and  to  near  the  tip  at  the  sides  and  inferior  part. 

It  contains  motor  fibres  to  the  stylo-pharyngeus,  the  constrictors 
of  the  pharynx,  and  probably  to  the  levator  palati  and  other  muscles 
of  the  palate,  except  the  tensor,  which  is  supplied  by  the  fifth  nerve. 
The  nerve  also  contains  fibres  concerned  in  common  sensation,  and 
the  sense  of  taste,  and  secretory  fibres  for  the  parotid  gland. 

The  cells  from  which  the  motor  fibres  originate  are  situated  in  a 
special  nucleus,  which  is  a  continuation  upwards  of  the  nucleus 
ambiguus  (the  chief  motor  nucleus  of  the  tenth  or  vagus  nerve).  The 
sensory  fibres  arise  in  the  jugular  and  petrosal  gangSa  from  cells  of 
the  spinal  ganglion  type.  When  the  central  axons  reach  the  bulb 
they  bifurcate  as  usual;  the  descending  branches  pass  down  the 
funiculus  solitarius  and  terminate  in  synapses  around  the  cells 
scattered  among  its  fibres.  The  ascending  branches  pass  almost 
horizontally  to  arborise  around  the  cells  of  the  principal  nucleus 
(IX.  in  fig.  408).  The  arrangement,  in  fact,  is  very  like  that  of  the 
tenth  nerve  now  to  be  described. 

The  tenth  nerve  (vagus  or  pneumo-gastric)  has  so  many  and 
important  functions  that  I  shall  not  attempt  to  describe  them  here ; 
it  would  mean  rewriting  a  great  deal  of  what  we  have  already  learnt 
in  connection  with  heart,  respiration,  digestion,  etc.  It  is  sufficient 
to  say  that  it  contains  both  efferent  and  afferent  fibres.  The  efferent 
fibres  arise  partly  from  the  upper  part  of  the  combined  nucleus,  which 
lower  down  gives  origin  to  the  spinal  accessory  nerve  (fig.  408,  X.)  but 
mainly  from  the  nucleus  ambiguus,  the  position  of  which  is  shown  in 
fig.  408,  coloured  blue,  and  also  in  transverse  section  in  figs.  412  and 
418.  The  afferent  fibres  originate  from  the  cells  of  the  ganglion  of 
the  trunk  and  of  the  root ;  they  enter  the  bulb  and  bifurcate ;  the 
ascending  branches  are  short  and  arborise  around  the  cells  of  the 
principal  nucleus  (X.  in  fig.  408) ;  the  descending  fibres,  together  with 
similar  ones  derived  from  the  glosso-pharyngeal  nerve,  and  pars 
intermedia,  pass  down  in  the  descending  root  of  vagus  and  glosso- 
pharyngeal,  which  is  also  known  as  the  funiculus  solitarius.  These 
fibres  terminate  by  arborising  around  the  cells  of  the  grey  matter 
that  lies  along  its  mesial  border  (descending  nucleus  of  vagus  and 


CH.  XLVI.]  THE    ELEVENTH   AND   TWELFTH   NERVES 


679 


glosso-pharyngeal).  This  approaches  the  middle  line  as  it  descends, 
and  finally  joins  that  of  the  opposite  side  over  the  central  canal 
(commissural  nucleus). 

The  eleventh  nerve  (spinal  accessory)  is  wholly  efferent :  it  arises 
by  two  distinct  origins — one  from  a  centre  in  the  floor  of  the  fourth 
ventricle,  and  connected  with  the  glosso-pharyngeal-vagus-nucleus ; 
the  other,  from  the  outer  side  of  the  anterior  cornu  of  the  spinal  cord 
as  low  down  as  the  fourth  cervical  nerve.  The  fibres  from  the  two 
origins  come  together  at  the  jugular  foramen,  but  separate  again  into 
two  branches,  outer  and  inner.  The  outer,  consisting  of  large 
medullated  fibres  from  the  spinal  origin,  supplies  the  trapezius  and 


cf.n.X  X/. 


Fio.  418.— The  tenth  and  twelfth  nerves,  pyr,  Pyramid  ;  n.XIL,  nucleus  of  hypoglossal ;  XII.,  fibre  of 
hypoglossal ;  d.n.X.XL,  combined  nucleus  of  vagus  and  spinal  accessory;  n.amb.,  nucleus 
ambiguus ; /.s.,  fasciculus  solitarius,  descending  fibres  of  vagus  and  glosso-pharyngeal ;  f.s.n.,  its 
nucleus;  X.,  motor  fibre  of  vagus ;  g,  ganglion  cell  in  vagus  trunk  giving  rise  to  a  sensory  fibre; 
d.  V.,  descending  root  of  the  fifth  nerve  ;  r,  restiform  body.  (Schiifer.) 

sterno-mastoid  muscles.  The  inner  branch,  consisting  of  small 
medullated  fibres  from  the  medulla,  supplies  chiefly  viscero-motor 
and  cardio-inhibitory  filaments  to  the  vagus.  The  muscles  of  the 
larynx,  all  of  which  are  supplied  by  branches  of  the  vagus,  derive 
their  motor  nerves  from  the  accessory;  Vrolik  states  that  in  the 
chimpanzee  the  internal  branch  of  the  accessory  does  not  join  the 
vagus  at  all,  but  goes  direct  to  the  larynx.  The  crico-thyroid,  how- 
ever, receives  fibres  which  leave  the  bulb  by  glosso-pharyngeal 
rootlets. 

The  twelfth  nerve  (hypoglossal)  is  also  entirely  efferent.  It  sup- 
plies the  muscles  of  the  tongue.  It  arises  from  a  large  celled  and  long 
nucleus  in  the  bulb,  close  to  the  middle  line  (see  figs.  408  and  418). 


CHAPTER   XLVII 

STRUCTURE   OF   THE   CEREBELLUM 

THE  cerebellum  is  composed  of  an  elongated  central  portion  or  lobe, 
called  the  vermis  or  vermiform  process,  and  two  hemispheres.  Each 
hemisphere  is  connected  with  its  fellow  by  means  of  the  vermiform 
process. 

The  cerebellum  is  composed  of  white  and  grey  matter,  the  latter 


Fia.  419. — Cerebellum  in  section  and  fourth  ventricle,  with  the  neighbouring  parts.  1,  median  groove 
of  fourth  ventricle,  ending  below  in  the  calamus  scriptorius,  with  the  longitudinal  eminences  formed 
by  the  fasciculi  teretes,  one  on  each  side;  2,  the  same  groove,  at  the  place  where  the  white  streaks 
of  the  auditory  nerve  emerge  from  it  to  cross  the  floor  of  the  ventricle  ;  3,  inferior  peduncle  of  the 
cerebellum,  formed  by  the  restiform  body  ;  4,  funiculus  gracilis ;  above  this  is  the  calamus  scrip- 
torius ;  5,  superior  peduncle  of  cerebellum ;  6,  6,  fillet  to  the  side  of  the  crura  cerebri ;  7,  V,  lateral 
grooves  of  the  crura  cerebri;  8,  corpora  quadrigemina.  (From  Sappey,  after  Hirschfeld  and 
Leveille.) 

being  external,  like  that  of  the  cerebrum,  and  like  it,  infolded,  so 
that  a  larger  area  may  be  contained  in  a  given  space.  The  convolu- 
tions of  the  grey  matter,  however,  are  arranged  after  a  different 
pattern,  as  shown  in  fig.  419.  The  tree-like  arrangement  of  the  white 


CH.  XLVII.]  THE   CEREBELLUM  681 

matter  on  section  has  given  rise  to  the  name  arbor  vitce.  Besides 
the  grey  substance  on  the  surface,  there  are,  in  the  centre  of  the 
white  substance  of  each  hemisphere,  small  masses  of  grey  matter,  the 
largest  of  which,  called  the  corpus  dentatum  (fig.  420,  cd),  resembles 
very  closely  the  corpus  dentatum  of  the  olivary  body  in  appearance. 


FIG.  420. — Outline  sketch  of  a  section  of  the  cerebellum,  showing  the  corpus  dentatum.  The  section 
has  been  carried  through  the  left  lateral  part  of  the  pons,  so  as  to  divide  the  superior  peduncle  and 
pass  nearly  through  the  middle  of  the  left  cerebellar  hemisphere.  The  olivary  body  has  also  been 
divided  longitiidinally  so  as  to  expose  in  section  its  corpus  dentatum.  cr,  Crus  cerebri  ;  /,  tillet ;  q, 
corpora  quadrigemina ;  sp,  superior  peduncle  of  the  cerebellum  divided ;  mp,  middle  peduncle  or 
lateral  part  of  the  pons  Varolii,  with  fibres  passing  from  it  into  the  white  stem  ;%w,  continuation 
of  the  white  stem  radiating  towards  the  arbor  vitai  of  the  folia  ;  cd,  corpus  dentatum ;  o,  olivary 
body  with  its  corpus  dentatum  ;  p,  pyramid.  (Allen  Thomson.)  §. 

In  a  section  through  the  cerebellar  cortex  the  following  layers 
can  be  seen. 

Underneath  the  pia  mater  is  the  external  layer  of  grey  matter;  it 
is  formed  chiefly  of  fine  nerve-fibres  with  small  nerve-cells  scattered 
through  it.  Into  its  outer  part,  processes  of  pia  mater  pass  verti- 
cally; these  convey  blood-vessels.  There  are  also  here  numerous 
long  tapering  neuroglia-cells.  The  internal  or  granular  layer  of  grey 
matter  is  made  up  of  a  large  number  of  small  nerve-cells  mixed  with 
a  few  larger  ones,  and  some  neuroglia-cells.  Between  the  two  layers 
is  an  incomplete  stratum  of  large  flask-shaped  cells,  called  the  cells 
of  Purkinje.  Each  of  these  gives  off  from  its  base  a  process  which 
becomes  the  axon  of  one  of  the  medullated  fibres  of  the  white  matter ; 
the  neck  of  the  flask  passing  in  the  opposite  direction  breaks  up  into 
dendrites  which  pass  into  the  external  layer  of  grey  matter.  By 
Golgi's  method  (fig.  421)  these  dendrons  have  been  shown  to  spread 
out  in  planes  transverse  to  the  direction  of  the  lamellae  of  the  organ. 

Each  cell  of  Purkinje  is  further  invested  by  arborisations  of  two 
sets  of  nerve-fibres.  One  of  these  (originating  from  the  fibres  of  the 
white  matter  which  are  not  continuous  as  axis-cylinders  from  the 
cells  of  Purkinje)  forms  a  basket-work  round  the  dendrons ;  the  other 
(originating  as  axis-cylinder  processes  from  the  nerve-cells  of  the 
external  layer)  forms  a  felt-work  of  fibrils  round  the  body  of  the 
cell. 

The  cells  of  the  internal  layer  of  grey  matter  are  small ;  their 


682 


STRUCTURE  OF  THE  CEREBELLUM 


[CH.  XLTII. 


dendrites  intermingle  with  those  of  neighbouring  cells ;  their  axons 
penetrate  into  the  external  layer,  but  their  final  destination  is 
uncertain.  Kamifying  among  these  cells  are  fibres  characterised  by 
possessing  bunches  of  short  branches  at  intervals  (moss-fibres  of 
Cajal). 

The  peduncles  of  the  cerebellum  are  three  in  number — superior, 
middle,  and  inferior ;  we  have  already  had  occasion  to  mention  them 
in  our  study  of  the  bulb,  pons,  and  mid -brain.  The  course  of  the 
fibres  has  been  chiefly  studied  by  the  degeneration  method. 

The  inferior  peduncle,  or  restiform  body,  is  composed  of  ascending 
fibres  which  pass  into  it  —  (1)  from  the  cerebellar  tracts  of  the 


FIG.  421.— Section  of  cerebellar  cortex,  stained  by  Golgi's  method  ;  I.  taken  across  the  lamina;  II.  in 
the  direction  of  the  lamina;  A,  outer  or  molecular  layer;  B,  inner  or  granular  layer ;  c,  white 
matter,  a,  Cell  of  Purkinje ;  &,  small  cells  of  inner  layer ;  c,  dendrons  of  these  cells ;  d,  axis- 
cylinder  process  of  one  of  these  cells  becoming  longitudinal  in  the  outer  layer  ;  e,  bifurcation  of  one 
of  these ;  g,  a  similar  cell  lying  in  the  white  matter.  (Ramon  y  Cajal.) 

same  side,  and  (2)  from  the  olivary  nucleus  of  the  opposite  side; 
(3)  possibly  a  few  fibres  from  the  nucleus  gracilis  and  nucleus 
cuneatus  also  join  it;  and  lastly,  (4)  it  receives  numerous  fibres 
from  the  vestibular  nerve,  or  from  the  nuclei  in  which  it  terminates 
in  the  pons.  The  inferior  peduncle  is  thus  mainly  a  spino-cere- 
bellar  path,  serving  by  the  cerebellar  tracts  to  unite  the  same 
side  of  the  cord  with  the  vermis,  and  the  opposite  side  of  the  cord 
with  the  cerebellar  hemisphere  via  the  opposite  olivary  nucleus  and 
reticular  formation  of  the  bulb. 

The  middle  peduncle  is  wholly  formed  of  fibres  which  originate 
from  the  cells  of  the  nuclei  pontis :  they  pass  from  one  side  of  the 
pons  to  the  opposite  cerebellar  hemisphere.  This  peduncle  is  the 
last  relay  of  the  cerebro-cerebellar  path. 


CH.  XLVII.]  CONNECTIONS   OF  THE   CEREBELLUM  683 

The  superior  peduncle :  the  axons  of  the  cells  of  Purkinje  mainly 
terminate  in  the  nucleus  dentatus,  and  the  other  subsidiary  masses 
of  grey  matter  situated  in  the  interior  of  the  cerebellum ;  from  the 
cells  of  these  nuclei  a  fresh  relay  of  fibres  issues,  conveying  impulses 
from  the  cerebellum  to  other  parts,  but  mainly  to  the  opposite 
cerebral  hemisphere ;  these  fibres  constitute  the  superior  cerebellar 
peduncle.  They  cross  the  middle  line,  give  off  numerous  collaterals 
to  the  red  nucleus  of  the  opposite  side,  and  also  to  the  nucleus  of  the 
opposite  third  nerve.  The  majority  terminate  in  the  optic  thalamus, 
whence  a  fresh  relay  continues  the  impulse  to  the  cerebral  cortex. 
This  therefore  is  the  cerebello -cerebral  path. 

After  the  fibres  of  the  superior  peduncle  have  crossed  the  middle 
line,  they  give  off  descending  branches  which  run  towards  the  bulb 
and  cord,  though  whether  they  reach  as  far  down  as  the  spinal  cord 
is  doubtful.  There  is,  however,  a  cerebello-spinal  path  ma  the  red 
nucleus  with  which  the  fibres  that  issue  from  the  cerebellum  com- 
municate after  crossing,  for  it  is  from  the  red  nucleus  that  the 
bundle  of  Monakow  arises  which  crosses  the  middle  line  and  is  seen 
in  the  cord  as  the  rubro-spinal  or  prepyramidal  tract ;  it  terminates 
in  the  anterior  horn  of  the  spinal  grey  matter.  The  cerebello-spinal 
path  therefore  exhibits  a  double  crossing;  the  first  is  that  of  the 
superior  peduncle  to  reach  the  opposite  red  nucleus,  and  the  second 
is  that  of  the  bundle  of  Monakow;  in  this  way  the  cerebellar  hemi- 
sphere is  linked  to  the  same  side  of  the  spinal  cord. 

In  addition  to  all  these  fibres,  the  superior  peduncle  also 
contains  some  fibres  of  the  spino  -  cerebellar  tracts,  which 
after  ascending  the  spinal  cord,  bulb  and  pons  turns  round  and 
course  back  along  the  superior  peduncle  into  the  cerebellum; 
these  fibres  are  distributed  mainly  to  the  lower  part  of  the 
vermis. 

The  next  figure  (fig.  422)  shows  the  principal  connections  of  the 
cerebellum  in  a  diagrammatic  way. 

Beginning  at  the  bottom,  we  see  one  of  the  cells  of  a  spinal 
ganglion  (s.G.)  sending  its  peripheral  axon  to  the  skin  (s.) ;  its  central 
axon  enters  the  spinal  cord  and  ascends  its  posterior  column,  to 
terminate  in  the  posterior  column  nuclei  of  the  bulb.  This  is  marked 
"to  Bulb."  This  is  the  first  segment  of  the  sensory  path  to  the 
cerebrum,  but  its  further  course  is  not  shown. 

The  entering  fibre  of  the  posterior  root  gives  off  collaterals  to  the 
spinal  grey  matter ;  some  of  these  pass  to  cells  in  the  posterior  horn 
(P.H.C.),  from  which  a  fresh  relay  carries  on  the  impulse  to  anterior 
horn  cells,  one  of  which  (A.H.C.)  is  seen  sending  its  axon  ma  the 
anterior  root,  to  end  in  the  muscular  fibre  M. 

Other  collaterals  terminate  by  synapses  around  the  cells  of 
Clarke's  column  (c.c.).  Two  of  these  cells  are  shown;  this  is  the 


684 


STRUCTURE   OF   THE   CEREBELLUM 


[CH.  XLVII. 


FIG.  422.— The  main  connections  of  the  cerebellum. 


CH.  XLVII.]  CONNECTIONS   OF  THE   CEREBELLUM  685 

first  cell-station  on  the  cerebellar  path.  One  of  these  is  represented 
as  giving  origin  to  a  fibre  of  the  direct  cerebellar  tract  (D.C.T.),  which 
enters  the  cerebellum  by  its  inferior  peduncle.  The  other  cell  of 
Clarke's  column  is  shown  giving  origin  to  a  fibre  of  Gowers'  tract 
(G.T.)  ;  it  is  represented  as  making  a  sharp  turn  after  having  reached 
its  highest  point,  and  enters  the  cerebellum  by  its  superior  peduncle ; 
both  of  these  spino-cerebellar  tracts  (coloured  blue  in  the  diagram) 
terminate  in  the  cortex  of  the  vermis ;  but  only  a  small  proportion 
of  their  fibres  take  the  roundabout  path  by  the  superior  peduncle 
(see  p.  658). 

Coming  next  to  the  middle  peduncle,  we  see  one  of  its  fibres 
(M.P.)  arising  from  a  cell  of  the  nucleus  pontis,  and  crossing  the 
middle  line  to  terminate  in  the  cortex  of  the  opposite  cerebellar 
hemisphere ;  entering  the  nucleus  pontis,  we  see  one  of  the  cortico- 
pontine  fibres  from  the  cerebrum  The  arrows  indicate  that  this  is 
the  path  (coloured  red  in  diagram)  by  which  impulses  reach  the 
cerebellum  from  the  cortex  of  the  cerebrum.  The  fibres  from  the 
cerebrum  to  the  nucleus  pontis  come  in  large  measure  from 
the  frontal  lobe  (see  next  chapter). 

The  superior  peduncle  is  more  complicated,  p  is  one  of  the  cells 
of  Purkinje  in  the  cortex  cerebelli ;  its  axon  passes  to  the  nucleus 
dentatus  of  the  cerebellum ;  from  the  cells  of  the  nucleus  dentatus 
fresh  axons  carry  on  the  impulse  to  the  optic  thalamus  of  the  opposite 
side  ;  one  of  these  fibres  (S.P.)  is  shown.  From  the  optic  thalamus  a 
fresh  relay  continues  the  impulse  to  the  cortex  cerebri.  Each  fibre 
of  the  superior  peduncle,  after  it  has  crossed  the  middle  line  (oo),  gives 
off  a  descending  branch  (D.),  the  destination  of  which  is  uncertain ;  it 
also  gives  off  branches  to  the  red  nucleus ;  from  the  cells  of  the  red 
nucleus  the  fibres  of  Monakow's  bundle  (M.B.)  continues  the  impulse 
down  to  the  anterior  horn-cells  of  the  opposite  side ;  owing  to  the 
double  crossing  the  cerebellar  hemisphere  is  thus  brought  into  connec- 
tion with  the  same  side  of  the  spinal  cord. 


CHAPTER  XLV1II 


STRUCTUKE  OF  THE  CEREBRUM 


THE  cerebrum  consists  of   two   halves,  called   cerebral  hemispheres, 
separated  by  a  deep  longitudinal  fissure  and  connected  by  a  large 


FIG.  423. — View  of  the  Corpus  Callosum  from  above.    J. — The  upper  surface  of  the  corpus  cal 
been  fully  exposed  by  separating  the  cerebral  hemispheres  and  throwing  them  to  the  side ; 


losum  has 
the  gyrus 

fornicatus  has  been  detached,  and  the  transverse  fibres  of  the  corpus  callosum  traced  for  some 
distance  into  the  cerebral  medullary  substance.  1,  the  upper  surface  of  the  corpus  callosum ;  2, 
median  furrow  or  raphe ;  3,  longitudinal  striae  bounding  the  furrow;  4,  swelling  formed  by  the 
transverse  bands  as  they  pass  into  the  cerebrum ;  5,  anterior  extremity  or  knee  of  the  corpus  cal- 
losum ;  6,  posterior  extremity ;  7,  anterior,  and  8,  posterior  part  of  the  mass  of  fibres  proceeding 
from  the  corpus  callosum ;  9,  margin  of  the  swelling ;  10,  anterior  part  of  the  convolution  of  the 
corpus  callosum;  11,  hem  or  band  of  union  of  this  convolution;  12,  internal  convolutions  of  the 
parietal  lobe  ;  13,  upper  surface  of  the  cerebellum.  (Sappey,  after  Foville.) 

band  of  transverse  commissural  fibres  known  as  the  corpus  callosum 
(fig.  423).     The  interior  of  each  hemisphere  contains  a  cavity  of  com- 


CH.  XLVIII.] 


STRUCTURE   OF   THE   CEREBRUM 


687 


plicated  shape,  called  the  lateral  ventricle ;  the  lateral  ventricles  open 
into  the  third  ventricle.  Fig.  424  represents  a  dissected  brain  in  which 
the  greater  part  of  the  corpus  callosum  has  been  removed;  the 
ventricles  are  thus  exposed. 

Each  hemisphere  is  covered  with  grey  matter,  which  passes  down 


FIG.  424. — Dissection  of  brain,  from  above,  exposing  the  lateral,  fourth,  and  fifth  ventricles  with  the 
surrounding  parts,  i. — a,  anterior  part,  or  genu  of  corpus  callosum  ;  b,  corpus  striatum  ;  &',  the 
corpus  striatum  of  left  .side,  dissected  so  as  to  expose  its  grey  substance  ;  c,  points  by  a  line  to  the 
taenia  semicircularis  ;  d,  optic  thalamus;  e,  anterior  pillars  of  fornix  divided  ;  below  they  are  seen 
descending  in  front  of  the  third  ventricle,  and  between  them  is  seen  part  of  the  anterior  commis- 
sure ;  in  front  of  the  letter  P,  is  seen  the  slit-like  fifth  ventricle,  between  the  two  laminae  of  the 
septum  lucidum  ;  /,  soft  or  middle  commissure ;  g  is  placed  in  the  posterior  part  of  the  third 
ventricle ;  immediately  behind  the  latter  are  the  posterior  commissure  (just  visible)  and  the  pineal 
gland,  the  two  crura  of  which  extend  forwards  along  the  inner  and  npper  margins  of  the  optic 
thalami ;  h  and  i,  the  corpora  quadrigemina ;  k,  superior  cms  of  cerebellum  ;  close  to  k  is  the  valve 
of  Vieussens,  which  has  been  divided  so  as  to  expose  the  fourth  ventricle ;  J,  hippocampus  maior 
and  corpus  fimbriatum,  or  taenia  hippocampi;  m,  hippocampus  minor;  n,  eminentia  collaterals  ; 
o,  fourth  ventricle;  p,  'posterior  surface  of  medulla  oblongata;  r,  section  of  cerebellum  ;  s,  upper  part 
of  left  hemisphere  of  cerebellum  exposed  by  the  removal  of  part  of  the  posterior  cerebral  lobe. 
(Hirschfeld  and  Leveille.) 

into  the  fissures.  This  surface  grey  matter  is  called  the  cerebral 
cortex.  The  amount  of  this  grey  matter  varies  directly  with  the 
amount  of  convolution  of  the  surface.  Under  it  white  matter  is 
situated ;  and  at  the  base  there  are  masses  of  grey  matter ;  part  of 
these  basal  ganglia  are  seen  forming  part  of  the  wall  of  the  ventricles. 
The  anterior  basal  ganglion  is  called  the  corpus  striatum;  it  is 


688 


STRUCTURE   OF   THE    CEREBRUM 


[CH.  XLVI11. 


divided  into  two  parts,  called  the  lenticular  or  extra-ventricular  nucleus, 
and  the  caudate  or  intra-ventricular  nucleus.  It  has  received  the 
latter  name  because  it  is  seen  in  the  interior  of  the  ventricle.  The 
posterior  basal  ganglion  is  called  the  optic  thalamus. 

Passing  up  between  the  basal  ganglia  are  the  white  fibres  which 
enter  or  leave  the  cerebral  hemisphere  by  the  crus ;  these  constitute 
the  internal  capsule.  This  passes  in  front  between  the  two  subdivi- 
sions of  the  corpus  striatum,  and  behind  between  the  optic  thalamus 
and  the  lenticular  nucleus  of  the  corpus  striatum. 

The  relationship  of  these  parts  is  best  seen  in  a  vertical  section ; 
such  as  is  represented  in  the  next  diagram  (fig.  425). 


FIG.  425.— Vertical  section  through  the  cerebrum  and  basal  ganglia  to  show  the  relations  of  the  latter, 
co.,  Cerebral  convolutions;  c.c.,  corpus  callosum  ;  v.L,  lateral  ventricle;  /,  fornix;  vIII.,  third 
ventricle;  n.c.,  caudate  nucleus;  th,  optic  tlialamus;  n.l.  .lenticular  nucleus  ;  c.i.,  internal  capsule; 
el.,  claustrum  ;  c.e.,  external  capsule  ;  m,  corpus  mammillare ;  t.o.,  optic  tract ;  s.t.t.,  stria  termin- 
alis ;  n.a.,  nucleus  amygdalae  ;  cm,  soft  commissure  ;  co.i.,  Island  of  Reil.  (Schwalbe.) 

One  hemisphere  is  seen,  with  portions  of  the  other.  The  surface 
darkly  shaded  indicates  the  grey  matter  of  the  cortex,  which  passes 
down  into  the  fissures ;  one  very  extensive  set  of  convolutions  (co.i.), 
passes  deeply  into  the  substance  of  the  hemisphere;  this  is  called 
the  Island  of  Eeil ;  the  lowest  stratum  of  grey  matter  is  separated 
from  this  to  form  a  narrow  isolated  strip  of  grey  matter  called  the 
claustrum  (cl.).  In  the  middle  line  the  great  longitudinal  fissure 
is  seen  extending  as  far  as  (c.c.)  the  corpus  callosum,  the  band  of 
white  matter  that  forms  the  great  commissure  between  the  two 
hemispheres;  beneath  this  are  the  lateral  ventricles  which  com- 
municate by  the  foramen  of  Munro  with  the  third  ventricle :  the 
fornix  is  indicated  by  the  letter  /.  Contributing  to  the  floor  of  the 
lateral  ventricle,  one  next  sees  the  optic  thakrnus  (th.),  and  the  tail 


CH.  XLV1II.]  STRUCTURE   OF   THE   CEREBRUM  689 

end  of  the  nucleus  caudatus  (n.c.) ;  the  section  being  taken  somewhat 
posteriorly.  The  nucleus  lenticularis  is  marked  nl. ;  and  the  band  of 
white  fibres  passing  up  between  it  and  the  thalamus  is  called  the 
internal  capsule  (c.i.)\  the  narrow  piece  of  white  matter  between 
the  claustrum  and  the  lenticular  nucleus  is  called  the  external 
capsule  (c.e.). 

For  the  student  of  medicine  the  internal  capsule  is  one  of  the 
most  important  parts  of  the  brain.  In  it  are  the  continuations  of 
the  fibres  which  we  have  previously  traced  as  far  as  the  crus  cerebri ; 
the  motor-fibres  of  the  crusta  are  continued  into  the  anterior  two- 
thirds  of  its  posterior  limb  (i.e.  behind  the  genu  *  in  fig.  426) ;  the 
sensory  fibres  of  the  tegmentum  into  the  posterior  third  of  this  limb. 
When  these  fibres  get  beyond  the  narrow  pass  between  the  basal 
ganglia,  they  spread  out  in  a  fan-like  manner  and  are  distributed  to 
the  grey  cortex ;  the  motor-fibres  come  down  from  the  motor  area  in 
front  of  the  fissure  of  Eolando ;  the  sensory  fibres  go  to  certain  con- 
volutions behind  this  fissure.  The  name  corona  radiata  is  applied 
to  the  fan-like  spreading  of  the  fibres;  the  fibres  as  they  pass 
through  the  handle  of  the  fan,  or  internal  capsule,  communicate 
with  the  nerve-cells  of  the  grey  matter  of  the  basal  ganglia;  the 
pyramidal  fibres  on  their  way  down  to  the  medulla  and  cord  from 
the  motor  area  of  the  brain  send  off  collaterals  or  side  branches 
which  arborise  around  the  cells  of  the  corpus  striatum,  and  to  a 
less  degree  around  those  of  the  optic  thalamus;  the  axis-cylinder 
processes  of  these  cells  pass  out  to  join  the  pyramidal  tract  on  its 
downward  course.  The  sensory  fibres  on  their  way  up  terminate 
by  arborising  round  the  cells  of  the  optic  thalamus,  and  in  the 
subthalamic  area.  This,  in  fact,  is  another  cell-station  or  position  of 
relay  :  the  fibres  passing  out  from  the  cells  of  the  thalamus  continue 
the  impulse  up  to  the  cortex. 

The  importance  of  the  internal  capsule  is  rendered  evident  when 
one  considers  the  blood  supply  of  these  parts ;  at  the  anterior  and 
posterior  perforated  spots,  numerous  small  blood-vessels  enter  for  the 
supply  of  the  basal  ganglia,  and  these  are  liable  to  become  diseased, 
and  if  they  rupture,  a  condition  called  apoplexy  is  the  result ;  if  the 
haemorrhage  is  excessive,  death  may  occur  almost  immediately ;  but 
if  the  patient  recovers,  a  condition  of  more  or  less  permanent  paralysis 
remains  behind ;  and  a  very  large  amount  of  paralysis  results  from  a 
comparatively  limited  lesion,  because  so  many  fibres  are  congregated 
together  in  this  narrow  isthmus  of  white  matter.  If  the  haemorrhage 
is  in  the  anterior  part  of  the  posterior  limb,  motor  paralysis  of  the 
opposite  side  of  the  body  (hemiplegia)  will  be  the  most  marked 
symptom.  If  the  haemorrhage  occurs  in  the  posterior  part,  sensory 
paralysis  of  the  opposite  side  of  the  body  will  be  the  most  marked 
symptom.  If  the  motor-fibres  are  affected,  degeneration  will  occur 

2  X 


690 


STRUCTURE  OF  THE  CEREBRUM 


[CH.  XLVIII. 


in  the  pyramidal  tract,  and  can  be  traced  through  the  pes  of  the  crus 
and  mid-brain  to  the  pyramid  of  the  pons  and  bulb,  and  then  in  the 
crossed  pyramidal  tract  of  the  opposite  side  and  in  the  direct  pyra- 
midal tract  of  the  same  side  of  the  cord. 

Fig.  426  represents  a  horizontal  view  through  the  hemisphere. 
The  internal  capsule  (c)  at  the  point  *  makes  a  bend  called  the  genu 


FIG.  426  —Diagram  to  show  the  connection  of  the  Frontal  and  Occipital  Lobes  with  the  Cerebellum,  etc. 
The  dotted  lines  passing  in  the  crusta  (T.OC.),  outside  the  motor  fibres,  indicate  the  connection 
between  the  temporo-occipital  lobe  and  the  cerebellum.  F.C.,  The  fronto-cerebellar  fibres,  which 
pass  anteriorly  to  the  motor  tract  in  the  crusta  ;  I.F.,  fibres  from  the  caudate  nucleus  to  the  pons. 
Fr. ,  frontal  lobe ;  Oc.,  occipital  lobe;  A. F.,  ascending  frontal;  AP.,  ascending  parietal  convolutions  ; 
PCF.,  precentral  fissure  in  front  of  the  ascending  frontal  convolution  ;  FR,  fissure  of  Rolando;  IFF., 
intraparietal  fissure.  A  section  of  the  crus  is  lettered  on  the  left  side.  S.N.,  Substantia  nigra ;  PV., 
pyramidal  motor  fibres,  which  on  the  right  are  shown  as  continuous  lines  converging  to  pass  through 
the  posterior  limb  of  i.e.,  internal  capsule  (the  knee  or  elbow  of  which  is  shown  thus  *)  upwards  into 
the  hemisphere  and  downwards  through  the  pons  to  cross  at  the  medulla  in  the  pyramidal  decussa- 
tion.  Ipt,  Crossed  pyramidal  tract ;  apt,  direct  pyramidal  tract.  (Gowers.) 

or  knee,  behind  which  the  motor-fibres,  and  more  posteriorly  still 
the  sensory-fibres,  pass.  Some  of  the  connections  between  cerebrum 
and  the  cerebellum  are  also  indicated. 

The  Convolutions  of  the  Cerebrum. 

The  surface  of  the  brain  is 'marked  by  a  great  number  of  depres- 
sions which  are  called  fissures  or  sulci,  and  it  is  this  folding  of  the 
surface  that  enables  a  very  large  amount  of  the  precious  material 
called  the  grey  matter  of  the  cortex  to  be  packed  within  the  narrow 
compass  of  the  cranium.  In  the  lowest  vertebrates  the  surface  of 
the  brain  is  smooth,  but  going  higher  in  the  animal  scale  the  fissures 
make  their  appearance,  reaching  their  greatest  degree  of  complexity 
in  the  higher  apes  and  in  man. 


CH.  XLV1II.]  THE  CONVOLUTIONS   OF  THE   CEREBRUM 


691 


In  an  early  embryonic  stage  of  the  human  foetus  the  brain  is  also 
smooth,  but  as  development  progresses  the  sulci  appear,  until  the 
climax  is  reached  in  the  brain  of  the  adult. 

The  sulci,  which  make  their  appearance  first,  both  in  the  animal 


FIG.  427. 

A.  Cerebral  Hemisphere  of  adult  Maeacque  monkey. 

B.  Cerebral  Hemisphere  of  child  shortly  before  birth. 

The  two  brains  are  very  much  alike,  but  the  growth  forwards  of  the  frontal  lobes  even  at  this  early 
stage  of  development  of  the  human  brain  is  quite  well  seen.  S.  fissure  of  Sylvius ;  B,  fissure  of 
Rolando. 

scale  and  in  the  development  of  the  human  foetus,  are  the  same. 
They  remain  in  the  adult  as  the  deepest  and  best-marked  sulci;  they 
are  called  the  primary  fissures  or  sulci,  and  they  divide  the  brain  into 


Fio.  428.— Brain  of  the  Orang,  jj  natural  size,  showing  the  arrangement  of  the  convolutions.  Sy,  fissure 
of  Sylvius ;  R,  fissure  of  Rolando ;  EP,  external  parieto-occipital  fissure  ;  Olf,  olfactory  lobe  ;  Cb, 
cerebellum  ;  PV,  pons  Varolii ;  MO,  medulla  oblongata.  As  contrasted  with  the  human  brain,  the 
frontal  lobe  is  short  and  small  relatively,  the  fissure  of  Sylvius  is  oblique,  the  teraporo-sphenoidal 
lobe  very  prominent,  and  the  external  parieto-occipital  fissure  very  well  marked.  Note  also  the 
bend  or  genu  in  the  Rolandic  fissure.  This  is  found  in  all  anthropoid  apes. 

lobes;   the   remaining   sulci,  called   the  secondary  fissures   or  sulci, 
further  subdivide  each  lobe  into  convolutions  or  gyri. 

A  first  glance  at  an  adult  human  brain  reveals  what  appears  to 
be  a  hopeless  puzzle ;  this,  however,  is  reduced  to  order  when  one 


692 


STRUCTURE  OF  THE  CEREBRUM 


[CH.  XLV1II. 


studies  the  brain  in  different  stages  of  development,  or  compares  the 
brain  of  man  with  that  of  the  lower  animals.  The  monkey's  brain 
in  particular  has  given  the  key  to  the  puzzle,  because  there  the 
primary  fissures  are  not  obscured  by  the  complexity  and  contorted 
arrangement  of  secondary  fissures. 

The  preceding  figure  (fig.  427),  comparing  the  brain  of  one  of  the 
lower  monkeys  with  that  of  the  child  shortly  before  birth,  shows  the 
close  family  likeness  in  the  two  cases. 

Fig.  428  gives  a  representation  of  the  brain  of  one  of  the  higher 
monkeys,  the  orang-outang,  where  there  is  an  intermediate  condition 
of  complexity  by  which  we  are  led  lastly  to  the  human  brain. 

Let  us  take  first  the  outer  surface  of  the  human  hemisphere ;  the 
primary  fissures  are — 

1.  The  fissure  of  Sylvius ;  this  divides  into  two  limbs,  the  posterior 
of  which  is  the  larger,  and  runs  backwards  and  upwards,  and  the 
anterior  limb,  which,  passing  into  the  substance  of  the  hemisphere, 
forms  the  Island  of  Eeil. 

2.  The  fissure  of  Rolando  (the  central  fissure)  runs  from  about 


R  O  N  TA  J. 


FIG.  429.— Eight  cerebral  hemisphere,  outer  surface. 

the  middle  of  the  top  of  the  diagram  (fig.  429),  downwards  and 
forwards. 

3.  The  external  parieto-occipital  fissure  (PAR.  oc.  F.)  is  parallel  to  the 
fissure  of  Eolando,  but  more  posterior  and  much  shorter ;  in  monkeys 
it  is  longer  (see  fig.  428),  as  it  is  not  interrupted  by  annectent  gyri. 

These  three  fissures  divide  the  brain  into  five  lobes : — 

1.  The  frontal  lobe, ;  in  front  of  the  fissure  of  Eolando. 

2.  The  parietal  lobe;  between  the  fissure  of  Eolando  and  the 
external  parieto-occipital  fissure. 

3.  The  occipital  lobe  ;  behind  the  external  parieto-occipital  fissure. 

4.  The  temporo-sphenoidal  lobe ;  below  the  fissure  of  Sylvius. 

5.  The  Island  of  Eeil. 

It  will  be  noticed  that  the  names  of  the  lobes  correspond  to  those 
of  the  bones  of  the  cranial  vault  which  cover  them.  There  is  no 


CH.  XLVIIL] 


THE  CEREBRAL   CONVOLUTIONS 


693 


exact  correspondence  between  the  bones  and  the  lobes,  but  the  precise 
position  of  the  various  convolutions  in  relation  to  the  surface  of  the 
skull  is  a  matter  of  anatomy  which,  in  these  days  of  brain-surgery, 
is  of  overwhelming  importance  to  the  surgeon.  The  position  of  a 
localised  disease  in  the  brain  can  be  determined  very  accurately,  as 
we  shall  see  later,  by  the  symptoms  exhibited  by  the  patient,  and  it 
would  be  obviously  inconvenient  to  the  patient  if  the  surgeon  was 
unable  to  trephine  over  the  exact  spot  under  which  the  diseased  con- 
volution lies,  but  had  to  make  a  number  of  exploratory  holes  to  find 
out  where  he  was. 

Each  lobe  is  divided  into  convolutions  by  secondary  fissures. 

1.  The  frontal  lobe  is  divided  by  the  central  frontal  or  precentral 
sulcus,  which  runs  upwards  parallel  to  the  fissure  of  Rolando,  and  two 
transverse  frontal  sulci,  upper  and   low^er,  into   four   convolutions; 
namely,  the  ascending  frontal  convolution,  in  front  of  the  fissure  of 
Rolando,  and  three  transverse  frontal  convolutions,  upper,  middle,  and 
lower,  which  run  outwards  and  forwards  from  it. 

2.  The  parietal  lobe  has  one  important  secondary  sulcus,  at  first 
running  parallel  to  the  fissure  of  Rolando  and  then  turning  back 
parallel  to  the  margin  of  the  brain.     It  is  called  the  intra-parietal 
sulcus.     The  lobe  is  thus  divided  into  the  ascending  parietal  convolu- 
tion behind  the  fissure  of   Rolando,  the  supra-marginal  convolution 
between  the  intra-parietal   sulcus,  and  the  fissure  of  Sylvius,  the 
angular  convolution  which  turns  round  the  end  of  the  Sylvian  fissure, 
and  the  superior  parietal  convolution,  or  parietal  lobule,  in  front  of  the 
external  parieto-occipital  fissure. 


UQBC 


Fio.  430.— Right  cerebral  hemisphere,  mesial  surface. 

3.  The  occipital  lobe  is  divided  into  upper,  middle,  and  lower 
occipital  convolutions  by  two  secondary  fissures  running  across  it. 

4.  The    temporal    or    temporo-sphenoidal    lobe    is    similarly 
divided  into  upper,  middle,  and  lower  temporal  convolutions  by  two 
fissures  running  parallel  to  the  fissure  of  Sylvius ;  the  upper  of  these 
fissures  is  called  the  parallel  fissure. 


694 


STRUCTURE  OF   THE   CEREBRUM 


[CH.  XLVIII. 


5.  The  Island  of  Reil  is  divided  into  convolutions  by  the  break- 
ing up  of  the  anterior  limb  of  the  Sylvian  fissure. 

Coming  now  to  the  mesial  surface  of  the  hemisphere  (fig.  430), 
its  subdivisions  are  made  evident  by  cutting  through  the  corpus 
callosum,  which  unites  the  hemisphere  to  its  fellow.  The  sub- 
division into  lobes  is  not  so  apparent  here  as  on  the  external 
surface  of  the  hemisphere,  so  we  may  pass  at  once  to  the  con- 
volutions into  which  it  is  broken  up  by  fissures. 

In  the  middle  the  corpus  callosum  is  seen  cut  across ;  above  it 
and  parallel  to  its  upper  border  is  a  fissure  called  the  calloso-marginal 
fissure,  which  turns  up  and  ends  on  the  surface  near  the  upper  end 
of  the  fissure  of  Eolando.  The  convolution  above  this  is  called  the 
marginal  convolution,  and  the  one  below  it  the  callosal  convolution  or 
gyrus  fornicatus.  The  deep  fissure  below  the  corpus  callosum  running 
from  its  posterior  end  forwards  and  downwards  is  called  the  dentate 
fissure;  this  forms  a  projection  seen  in  the  interior  of  the  lateral 
ventricle,  and  called  there  the  hippocampus  major ;  the  hippocampal 
convolution,  together  with  the  gyrus  fornicatus  above  the  corpus 
callosum,  constitutes  the  limbic  lobe.  Bolow  the  dentate  fissure  is 
another  called  the  collateral  fissure,  above  which  is  the  uncinate 
convolution,  and  below  which  is  the  inferior  temporal  convolution 
which  we  have  previously  seen  on  the  external  surface  of  the 
hemisphere  (see  fig.  429).  In  the  occipital  region  the  internal  parieto- 
occipital  fissure,  which  is  a  continuation  of  the  external  parieto-occipital 
fissure,  passes  downwards  and  forwards  till  it  meets  the  calcarine 
fissure,  which  is  a  primary  fissure ;  these  two  enclose  between  them  a 
wedge-shaped  piece  of  brain  called  the 
cuneus  or  cuneate  lobule;  the  square 
piece  above  it  is  called  the  precuneus 
or  quadrilateral  lobule. 

The  only  convolutions  now  left  are 
those  which  are  placed  on  the  surface 
of  the  frontal  lobe  that  rests  on  the 
orbital  plate  of  the  frontal  bone ;  they 
are  shown  in  fig.  395,  2  %  2"  (p.  642), 
and  may  be  seen  diagrammatically  in 
fig.  431,  the  end  of  the  temporal  lobe 
being  cut  off  to  expose  the  convolu- 
tions of  the  central  lobe  or  Island  of 
Eeil. 

Along  the  edge  is  the  continuation 
of  the  marginal  convolution  (M);  next  comes  the  olfactory  sulcus 
(o),  in  which  the  olfactory  tract  and  bulb  lie;  then  the  triradiate 
orbital  sulcus  (o.s.),  which  divides  the  rest  of  this  surface  into  three 
convolutions. 


A.P.S 


FIG.  431.— Orbital  surface  of  frontal  lobe. 

M,  marginal  convolution. 

0,  olfactory  sulcus. 
O.S.,  orbital  sulcus. 

1,  Island  of  Reil. 

S.a.,  anterior  limb  of  Sylvian  fissure. 
S.p.,  posterior  limb  of  Sylvian  fissure. 
A.P.S.,  anterior  perforated  spot. 


CH.  XLV11I.] 


STRUCTURE   OF   THE   CORTEX 


695 


Histological  Structure  of  the  Cerebral  Cortex. 

The  possibility  of  differentiating  the  cerebral  cortex  in  relation 
to  its  functions  took  origin  in  the  work  of  Bevan  Lewis  and  Henry 
Clarke  in  1878,  and  the  subject  has  in  recent  years  received  attention 


Fin.  432.— The  layers  of  the  conical  grey 
matter  of  the  cerebrum.    (Mey nert. ) 


H 


Fio.  433.— Principal  types  of  cells  in  the 
cerebral  cortex. 

A,  medium-sized   pyramidal    cell    of   the 
second  layer. 

B,  large  pyramidal  cell. 

C,  polymorphic  cell. 

D,  cell  of  which  the  axis- cylinder  process  is 

ascending. 

E,  neuroglia  cell. 

F,  cell  of  the  first  layer,  forming  an  inter- 

mediate cell-station  between  sensory 
fibres  and  motor  cells.  Notice  the 
tangential  direction  of  the  nerve- 
fibres. 

G,  sensory  fibre  from  the  white  matter. 
11,  white  matter. 

1,  collateral  of  the  white  matter.    (Ramon 
y  Cajal.) 


at  the  hands  of  A.  W.  Campbell,  Brodmann  J.  S. •  Bolton,  and  others. 
Certain  main  features  have  been  established,  although  unanimity  on 
the  interpretation  of  all  the  facts  has  not  yet  been  reached. 


696 


STRUCTURE  OF  THE  CEREBRUM 


[CH.  XLVIII. 


The  cortex  may  be  divided  into  five  primary  laminae : — 

1.  The  outer  fibre  layer   or  superficial  lamina. — The   fibres  are 
largely  derived  from  the  dendrons  of  the  cells  of  the  next  layer.     The 
nerve-cells  (F  in  fig.  433)  intermingled  with  these  are  branched,  and 
have  several   processes  which  lie   horizontally  beneath  the  surface 
(tangential  fibres).     There   are   doubtless   association  units  linking 
the  incoming  afferent  neurons  to  those  which  are  motor.     Neuroglia 
cells  are  also  present. 

2.  The  outer  cell  lamina  or  layer  of  small  pyramids. — There  are 
several  deep,  and  the  largest  cells  are  situated  most,  deeply.     Each  of 
these   has  an  apical   process   running   to   the   surface,   where    the 
branches  run  tangentially.     The  lateral  processes  are  also  branched 


FIG.  434.— Human  cerebral  cortex :  Golgi's  method.    Low  power.    (Mott.) 

dendrons.  The  axon  originates  from  the  base.  The  layer  of  small 
pyramids  increases  in  depth  as  we  ascend  the  animal  scale.  They 
are  believed  to  be  association  units  subserving  the  higher  mental 
processes. 

3.  The  middle  cell  lamina  (numbered  4  in  figure  432). — This 
consists  of  small  cells  called  granules.  This  layer  is  a  distinguishing 
mark  of  sensory  areas,  and  is  practically  absent  in  the  pre-Eolandic 
or  motor  convolutions. 

4.^  The  inner  fibre  layer. — In  certain  regions  of  the  cortex  this 
contains  the  giant  pyramids  or  Betz  cells,  which  are  characteristic 
of  the  motor  areas.  In  the  visual  cortex  the  so-called  solitary  cells 
of  Meynert  are  present  here. 


CH.  XLVIIL] 


STRUCTURE  OF  THE   CORTEX 


697 


5.  The  inner  cell  lamina  or  polymorphic  layer. — These  are  small 
scattered  cells,  many  of  a  fusiform  shape.  In  the  Island  of  Eeil  this 
layer  is  hypertrophied,  and  is  separated  from  the  rest  of  the  grey 
matter  by  a  stratum  of  white  fibres;  it  is  known  then  as  the 
claustrum. 

The  G-olgi  method  of  staining  has  proved  conspicuously  useful  for 
studying  the  shapes  and  dispositions  of  the  cells  (figs.  433,  434,  435). 

Nerve-fibres  pass  in  vertical  streaks  through  the  deeper  layers  of 
the  grey  matter ;  some  of  these  are  axons  conveying  impulses  down- 
wards, others  are  sensory  in  function  and  carry  impulses  upwards. 
Some  strands  lie  parallel  to  the  surface  of  the  cortex;  this  is 
specially  noticeable  in  the  layers  we  have  numbered  1  and  4.  In 


FIG  435.—  II  tman  cerebral  cortex,  showing  a  Betz  cell  or  giant  pyramid :  Golgi's  method. 
High  power.    (Mott.) 

the  portion  of  the  occipital  lobe  which  is  the  visual  sphere,  the 
granule  layer  (No.  3),  which  is  so  specially  characteristic  of  sensory 
function,  is  of  great  depth  and  is  divided  into  two  by  optic  radiations 
running  horizontally,  which  constitute  the  white  line  of  Gennari. 

Bolton  regards  the  fifth  lamina  as  the  fundamental  cell  layer,  the 
others  being  formed  from  it  from  within  outwards,  both  in  embryonic 
and  historical  development.  Defect  of  development  of  the  outer  layers 
leads  to  various  forms  of  amentia  (inborn  lack  of  mental  develop- 
ment, or  idiocy) ;  in  dementia  (degenerative  mental  change  coming 
on  later  in  life)  there  are  retrograde  changes  in  the  upper  layers  of 
cells.  The  fifth  or  inner  cell  layer  is  probably  concerned  with  the 
performance  of  organic  and  instinctive  activities,  and  there  is  but 


698  STRUCTURE  OF  THE   CEREBRUM  [CH.  XLY1II. 

little  difference  seen  here  between  man,  monkey,  and  dog.  The 
second  layer,  on  the  other  hand,  is  concerned  with  the  psychic  or 
associational  functions,  and  attains  its  maximum  depth  in  man. 

The  archipallium  (p.  646)  is  the  portion  of  the  cortex  which 
makes  it  appearance  earliest  in  vertebrates,  and  is  associated  with 
the  rhinencephalon  or  olfactory  lobe  of  the  pala-encephalon.  In 
mammals  it  is  reduced  to  small  proportions  in  comparison  with  the 
rest  of  the  cortex,  which  is  termed,  on  account  of  its  later  appearance 
in  historical  development,  the  neopallium.  In  man,  the  archipallium 
is  doubled  in  to  form  the  hippocampus  major,  which  projects  into  the 
lateral  ventricle;  this  is  continuous  externally  around  the  dentate 
sulcus  with  the  gyrus  hippocampi.  This  part  of  the  cortex  is  easily 
distinguishable  from  the  neopallium,  being  much  simpler  in  structure 
— the  pyramids,  for  instance,  are  reduced  to  a  single  layer,  and  the 
smaller  cells  nearer  the  surface  are  grouped  in  a  characteristic  nest- 
like  way. 

The  White  Matter  of  the  Cerebrum. 

The  white  matter  of  the  cerebrum,  like  white  matter  elsewhere,  is 
made  up  of  medullated  nerve  fibres.  According  to  the  direction  of 
the  fibres,  they  may  be  divided  into  three  principal  groups : — 

1.  Association  fibres. — These  pass  from  convolution  to  convolution, 
and  the  principal  bundles  of  these  are  shown  semi-diagrammatically 
in  fig.  436. 

2.  Commissural  fibres. — These   pass  by   the   commissures  of  the 
brain,  of  which  the  most  important  is  the  corpus  callorum,  so  as  to 
link  the  convolutions  of  one  hemisphere  with  the   corresponding 
convolutions  in  the  opposite  hemisphere,  where  they  terminate  in 
arborisations  (synapses)  around  the  cells  of  the  grey  cortex. 

3.  Projection  fibres. — These   are   the  fibres  which   run  more  or 
less  vertically  and  link  the  cerebrum  to  the  lower  portions  of  the 
central^  nervous  system.     They  may  be  subdivided  into  the  efferent 
projection  fibres,  which  convey  impulses  downwards,  and  the  afferent 
projection  fibres,  which  convey  impulses  upwards.     They  are  shown 
semi-diagrammatically  in  fig.  437. 

The  term  projection  fibre  almost  explains  itself.  By  means  of 
the  efferent  projection  system  the  cerebrum  is  able  to  project  its 
impulses  to  the  cord,  and  thence  to  the  muscles  at  the  periphery. 
By  means  of  the  afferent  projection  system  the  surface  of  the  body, 
provided  as  it  is  with  sense  organs,  is  able  to  project  its  impulses  to 
the  seat  of  sensation. 

The  efferent  projection  system. — The  most  important  portion  of 
this  is  the  cerebro-spinal  motor  tract.  The  cells  of  the  cortex  which 
give  rise  to  these  fibres  are  par  excellence  the  Betz  cells,  which  are 
found  in  the  fourth  layer  in  the  region  of  the  brain,  known  as  the 


CH.  XLV11I.] 


THE   PROJECTION   FIBRES 


699 


Fid.  436.— Lateral  view  of  a  human  hemisphere,  showing  the  main  bundles  of  association  fibres  (Starr). 
A,  A,  between  adjacent  convolutions  ;  B,  between  frontal  and  occipital  areas  ;  C,  between  frontal 
and  temporal  areas  (cingulum) ;  D,  between  frontal  and  temporal  areas  (fasciculus  uncinatus)  ;  E, 
between  occipital  and  temporal  areas  (fasciculus  longitudinalis  inferior) ;  C.N.,  caudate  nucleus; 
O.T.,  optic  thalamua. 


Fio.  437.— Schema  of  the  projection  fibres  within  the  brain  (Starr).  A,  tract  from  the  frontal  gyri  to  the 
pons  nuclei  and  so  to  the  cerebellum ;  B,  motor  pyramidal  tract ;  C,  sensory  tract  for  touch  ; 
D,  visual  tract;  E,  auditory  tract;  F,  G,  H,  superior,  middle,  and  inferior  cerebellar  peduncles;  J, 
fibres  between  the  auditory  nucleus  and  the  inferior  corpus  quadrigeminum  ;  K,  motor  decussation 
in  the  bulb  ;  F.V.,  fourth  ventricle.  The  numerals  refer  to  the  cranial  nerves.  The  sensory  radia- 
tions are  seen  to  be  massed  towards  the  occipital  end  of  the  hemisphere. 


700  STRUCTURE  OF  THE  CEREBRUM         [CH.  XLVTII. 

motor  area  (the  convolutions  immediately  in  front  of  the  Eolandic 
fissure).  The  axon  of  each  of  these  giant  pyramids  originates  from 
its  base,  and  fig.  438  (next  page)  shows  in  outline  the  destination 
of  the  fibres. 

1  is  a  cell  of  the  motor  or  Eolandic  area  of  the  cerebral  cortex ; 
its  axon  (Ax)  passes  down  in  the  pyramidal  tract,  and  crosses  the 
middle  line  (oo)  at  the  pyramidal  decussation.  It  gives  off  collaterals, 
one  of  which  (assoc.)  is  an  association  fibre  passing  to  terminate  in 
the  cortex  of  a  neighbouring  convolution ;  another,  labelled  commis,  is 
a  commissural  fibre  passing  in  the  corpus  callosum  to  the  opposite 
hemisphere ;  others  pass  into  basal  ganglia. 

In  the  cord,  collaterals  pass  off  to  end  in  synapses  around  cells 
at  the  base  of  the  posterior  horn,  and  the  main  fibre  has  a  similar 
termination;  from  each  of  these  posterior  horn  cells,  a  short  axon 
passes  to  end  in  an  arborisation  around  an  anterior  cornual  cell; 
only  one  of  these  is  shown ;  the  motor  nerve-fibre  passes  from  this 
to  muscular  fibres,  to  terminate  in  end-plates  there. 

The  pyramidal  cell  numbered  2  is  taken  to  illustrate  the  similar 
relationships  between  the  cortex  and  muscles  supplied  by  cranial 
nerves ;  its  axon  is  represented  as  ending  in  the  motor  nucleus  of 
the  seventh  nerve,  and  the  new  axon  arising  there  passes  to  face- 
muscles.  In  order  to  prevent  confusion  in  the  diagram,  cell  2  is 
placed  in  one  of  the  upper  convolutions ;  the  face  area  of  the  cortex 
is  really  below  those  for  the  limbs. 

The  cell  numbered  3  illustrates  the  fact  that  certain  axons  never 
reach  the  spinal  cord,  but  terminate  in  the  grey  matter  of  the  mid- 
brain  and  pons ;  such  fibres  may  therefore  be  called  cortico-pontine, 
in  contradistinction  to  the  pyramidal  fibres,  which  are  cortico-spinal. 
From  these  subsidiary  masses  of  grey  matter  in  the  pons  and  mid- 
brain,  new  tracts,  such  as  the  bundle  of  Monakow  or  prepyramidal 
tract,  arise  (ponto-spinal  fibres),  which  continue  on  the  impulse  to  the 
anterior  cornual  cells. 

No  attempt  has  been  made  in  this  diagram  to  insert  autonomic 
fibres  with  their  accessory  cell-stations  in  ganglia  outside  the 
central  nervous  systems.  For  these  the  reader  is  referred  back  to 
Chap.  XVII. 

The  afferent  projection  system. — This  is  also  indicated  in  outline 
in  the  same  diagram  (fig.  438).  A  is  a  cell  of  one  of  the  spinal 
ganglia  on  the  posterior  nerve-roots;  its  peripheral  axon  terminates 
in  muscular  tendons  or  in  skin,  and  the  impulse  it  conducts  is 
afferent,  as  shown  by  the  arrow.  The  central  axon  passes  into 
the  spinal  cord,  and  its  impulse  ultimately  arrives  at  the  cortex  of 
the  opposite  side  through  several  intermediate  cell-stations.  The 
last  relay  on  the  sensory  path  passes  from  O.T.,  the  optic  thalamus, 
to  the  cortex,  and  is  linked  up  to  the  motor  cell  (1)  by  the  associa- 


CH.  XLV1IL]      AFFERENT  TRACTS  TO  THE  CORTEX 


701 


tion    unit   (4)  in   the    superficial   layer   of   the  grey  matter.      Its 
intervening  course  from  spinal  ganglion  to  optic  thalamus  is,  to  save 
confusion  in  the  diagram,  represented  by  a  dotted  line.     The  diagram 
on  the  next  page  (fig.  439)  fills  in  the  details  of  the  sensory  path. 
Beginning  at  the  lower  part  of  the  diagram  (fig.  439)  on  the  right- 


FACE  MUSCLE 


Fia.  488.— Diagram  of  the  principal  efferent  channels. 

hand  side,  we  see  one  of  the  cells  of  a  spinal  ganglion.  Its  central 
axon  enters  the  cord,  runs  up  the  posterior  column,  and  terminates  in 
one  or  other  of  the  dorsal  column  nuclei  (gracilis  or  cuneatus) ;  the  new 
axons  arising  there,  called  arcuate  fibres,  cross  the  middle  line  and 
ascend  as  fibres  of  the  main  fillet  to  the  optic  thalamus ;  from  which, 
as  we  have  seen,  a  new  relay  carries  on  the  impulse  to  the  cortex. 


702 


STRUCTURE  OF  THE  CEREBRUM        [CH.  XLVIII. 


Corp.  (fuadr.  posterior 


Ga/nglion  -  cell 
of  cerebral  nerve  (  Vth.) 


Thala,mus 


Fibre.from  sensory 
nucleus  qf  cerebral- 
uerve(Vth.)to  Ihalcunus 


Upper  or  main 
fillet 


Fibre 

or  lateral  fiU^et  — 
to  corp.  cfuadr  post. 


Fibre  of  main 


fillet  to  thalamus 


Fibre  from  cord 
to  thalamus. 


HedioM 
•plan 

FIG.  439.— Diagram  of  principal  sensory  channels.    (B.  A.  Schafer.) 


CH.  XLVIII.]       AFFERENT  TRACTS  TO  THE  CORTEX  703 

In  the  cord,  however,  it  gives  off  many  collaterals,  some  of  which 
arborise  around  anterior  horn  cells  of  the  same  or  the  opposite  side, 
to  form  the  basis  of  spinal  reflex  action.  Others  are  shown  crossing 
the  middle  line,  and  they  ultimately  reach  the  thalamus  by  the 
ascending  tracts  of  the  opposite  side  of  the  spinal  cord  and  bulb. 

The  arrangement  of  the  sensory  cranial  nerves  is  very  similar ;  a 
cell  of  the  Gasserian  ganglion  is  seen  sending  its  peripheral  axon  to  the 
face  region  in  the  fifth  nerve,  and  its  central  axon  to  arborise  around 
the  cells  of  the  sensory  nucleus  of  the  fifth  nerve  in  the  bulb.  From 
these  cells  the  second  relay  carries  on  the  impulse  to  the  thalamus. 

The  arrangement  of  the  cochlear  nerve  is  very  similar ;  the  second 
relay,  via  trapezium  and  lateral  fillet,  carries  the  impulse,  however,  to 
the  posterior  corpus  quadrigeminum  instead  of  to  the  optic  thalamus ; 
a  third  relay,  not  shown  in  the  diagram,  completes  the  journey  from 
this  mass  of  grey  matter  to  the  cortex. 

The  connections  of  the  cord  and  cerebrum  to  the  cerebellum  we 
have  previously  studied  (see  fig.  422,  p.  684),  and  so  they  are  not 
shown  in  the  present  diagrams. 

Particular  attention  should  be  paid  to  the  following  point :  when 
an  afferent  fibre  enters  the  spinal  cord,  it  divides  into  three  main 
sets  of  branches.  The  first  set,  the  shortest,  forms  synapses  with 
the  motor  cells  of  the  anterior  horn ;  here  we  have  the  anatomical 
basis  of  spinal  reflex  action.  The  second  set  passes  through  an 
intermediate  cell-station  in  Clarke's  column  to  the  cerebellum,  the 
emerging  fibres  from  which  also  influence  the  motor  discharge  of 
the  cortical  and  anterior  horn  cells.  The  third  set,  the  longest, 
passes  through  three  intermediate  cell-stations  (the  first  in  the 
nucleus  gracilis  or  cuneatus,  the  second  in  the  optic  thalamus,  the 
third  in  the  association  units  in  the  cortex),  and  ultimately  reaches 
the  pyramidal  nerve-cells  of  the  cerebral  cortex,  the  efferent  fibres 
(pyramidal  fibres)  of  which  pass  to  the  motor  cells  of  the  anterior 
cornu  and  influence  their  discharge.  The  motor  nerve-cells  of  the 
anterior  horn  may  thus  be  influenced  by  the  afferent  impulses 
via  three  paths  or  nervous  circles.  In  health,  all  these  nervous 
circles  are  in  action  to  produce  coordinated  muscular  impulses.  In 
locomotor  ataxy,  which  is  a  degeneration  of  the  cells  of  the  ganglia 
on  the  posterior  roots  and  their  branches,  all  these  nervous  circles 
are  deranged,  and  the  result  is  loss  of  reflex  action,  and  incoordina- 
tion  of  muscular  movements. 


CHAPTEE  XLIX 

FUNCTIONS   OF  THE   SPINAL  CORD 

THE  functions  of  the  spinal  cord  fall  into  two  categories  :  functions 
of  the  grey  matter,  which  consist  in  the  conversion  of  afferent  into 
efferent  impulses  (reflex  action) ;  and  functions  of  the  white  matter, 
which  are  those  of  conduction. 

The  Cord  as  an  Organ  of  Conduction. 

The  fibres  of  the  spinal  cord  consist  of  three  main  groups ;  these 
are — (1)  the  association  tracts,  which  connect  together  different 
segments  of  the  cord  and  thus  bring  about  coordination  of  the 
impulses,  which  leave  it  at  various  levels,  in  relationship  to  the 
impulses  which  enter  the  cord  either  below  or  above  any  particular 
region ;  (2)  the  efferent  projection  fibres,  which  connect  the  cord  with 
the  different  parts  of  the  brain  above  it.  The  main  motor  path,  the 
pyramidal  tract,  comes  into  this  category ;  and  after  our  full  descrip- 
tion of  its  course,  we  need  not  do  more  here  than  remind  the  reader 
that  it  originates  from  the  giant  pyramids  of  the  motor  area  of  the 
cortex,  and  that  its  fibres  cross  to  the  opposite  side  of  the  spinal 
cord,  the  principal  decussation  occurring  at  the  lowest  level  of  the 
bulb ;  from  the  grey  matter  in  which  it  terminates  in  the  cord,  the 
impulse  is  continued  onwards,  until  in  the  end  it  reaches  the  muscles 
via  the  fibres  which  leave  the  cord  in  the  anterior  nerve-roots ;  (3) 
the  afferent  projection  system  of  fibres;  these  primarily  enter  the 
cord  by  the  posterior  spinal  nerve-roots.  The  impulses  which  these 
convey  enter  (a)  the  spinal  grey  matter,  (6)  the  cerebellum,  and  (c) 
the  cerebrum,  the  seat  of  consciousness. 

It  is  these  sensory  tracts  which  are  the  most  complex,  not  only 
on  account  of  the  cell-stations  in  their  course,  but  also  on  account  of 
the  difficulty  of  determining  in  animals  the  different  kinds  of  sensa- 
tions which  are  present  in  health,  or  which  may  be  absent  after 
injury  to  various  tracts.  It  is,  however,  certain  that  ultimately,  so 
far  as  the  cerebrum  is  concerned,  crossing  occurs  somewhere,  so  that 

704 


CH.  XLIX.]  CONDUCTION   IN  THE  COED  705 

each  hemisphere  is  related  to  the  opposite  half  of  the  body,  not  only 
in  regard  to  motion  but  in  regard  to  sensation  also.  The  main 
difficulty  of  investigators  has  been  to  determine  exactly  where  the 
crossing  occurs;  in  man  especially,  many  of  the  impulses  cross 
shortly  after  their  entry  into  the  cord,  and  then  travel  up  to  the 
higher  centres  by  paths  on  the  opposite  side  of  the  cord  to  that  by 
which  they  enter.  In  such  investigations  on  man,  various  injuries 
to  the  cord  have  to  be  carefully  studied,  and  it  is  such  careful  study 
that  has  led  to  this  conclusion. 

For  fifty  years,  physiologists,  stimulated  by  the  work  of  Brown- 
Sequard,  have  attempted  to  trace  the  upward  paths  of  afferent 
impulses  through  the  spinal  cord.  By  experiments  on  animals,  the 
secondary  ascending  degenerations  which  follow  injury  can  be  fol- 
lowed with  exactitude,  and  traced  into  bulb,  cerebrum,  cerebellum, 
or  other  parts.  But  even  though  such  animals  may  be  long  under 
observation,  they  cannot  tell  us,  and  we  can  only  with  difficulty 
and  ill-success  guess,  how  their  sensations  are  affected  by  the  lesion. 

On  the  other  hand,  the  clinical  observer  may  expend  much 
time  and  trouble  in  determining  the  nature  of  the  loss  of  sensation, 
but  it  is  usually  impossible  to  verify  the  anatomical  position  and 
nature  of  the  lesion.  In  many  cases  where  a  microscopical  examina- 
tion has  been  made,  the  disease  has  been  of  a  progressive  nature,  or 
the  patient  has  died  from  complications,  which  detract  from  his 
suitability  for  an  examination  of  this  kind. 

Nevertheless,  by  a  combination  of  the  experimental  and  clinical 
methods,  we  have  now  arrived  at  some  accuracy  on  these  points,  and 
it  is  impossible  to  overestimate  in  this  direction  the  value  of  the 
psycho-physical  examination  of  patients  which  has  within  the  last 
few  years  been  made  by  Head,  Eivers,  and  Sherren. 

In  order,  however,  to  examine  the  sensations  of  a  patient,  it  is 
necessary  to  know  first  how  to  classify  the  sensations  which  are  the 
result  of  cutaneous  stimulation.  To  do  this,  we  must  somewhat 
anticipate  what  we  shall  go  into  more  fully  in  the  chapter  on  the 
Cutaneous  Senses.  It  has  been  proved  that,  scattered  over  the 
external  surface  of  the  body,  are  a  number  of  spots,  some  which  are 
more  susceptible  to  one  form  of  stimulus  than  others.  The  spots  are 
of  four  kinds,  known  as  touch  spots,  pain  spots,  heat  spots,  and  cold 
spots,  and  these  correspond  to  the  four  kinds  of  sensations  which  we 
experience  as  the  result  of  cutaneous  excitation.  They  correspond 
to  different  kinds  of  end-organs  in  the  skin,  and  the  impulses  are 
carried  to  the  central  nervous  system  by  different  groups  of  fibres. 

Dr  Head  found,  from  an  experiment  he  made  by  cutting  a  sensory 
cutaneous  nerve  in  his  own  arm,  that  although  the  patch  of  skin 
supplied  by  the  nerve  was  entirely  destitute  of  sensation,  the  under- 
lying parts  were  still  sensitive  to  pressure  and  to  pain.  These  deep 

2  Y 


706  FUNCTIONS   OF  THE   SPINAL  CORD  fCH.  XL1X. 

sensations  are  subserved  by  nerve-fibres  which  are  distributed  with 
the  muscular  nerves.  It  is  by  means  of  the  sensory  nerves  of  muscles, 
tendons,  and  joints  that  we  are  aware  of  the  position  of  our  limbs, 
and  the  extent  of  muscular  contraction. 

After  a  time  true  cutaneous  sensation  returned  when  the  severed 
nerve  regenerated,  but  it  was  not  until  many  months  elapsed  that 
sensation  was  as  sharp  and  as  accurately  localised  as  it  was  before 
the  nerve  had  been  cut.  The  first  sensations  that  returned  enabled 
Head  to  feel  pain,  to  distinguish  large  differences  of  temperature, 
and  to  localise  the  position  of  a  touch  somewhat  inaccurately.  Head 
terms  such  imperfect  sensations  protopathic.  The  ability  to  localise 
accurately,  to  distinguish  small  differences  of  temperature  and  the 
finer  distinctions  generally  of  cutaneous  sensations,  returned  later, 
and  are  spoken  of  as  epicritic.  We  may  thus  divide  the  main  sensa- 
tions coming  from  the  periphery  of  the  body  into  deep  and 
cutaneous ;  and  the  cutaneous  sensations  into  protopathic  and  epi- 
critic. The  other  classification  into  sensations  of  touch,  heat,  cold, 
and  pain,  cuts  across  the  first;  thus  we  may  have  pain  that  is  of 
deep  or  of  cutaneous  origin ;  we  may  have  temperature  sensations 
which  are  both  rough  or  protopathic,  and  accurate  or  epicritic ;  and 
we  may  feel  pressure  and  localise  it  by  means  of  the  cutaneous  sense 
proper,  or  by  the  stimulation  of  the  sensory  nerves  in  the  deeper 
structures.  Whether  different  nerve-fibres  are  concerned  in  the 
transmission  of  protopathic  and  epicritic  impulses  is  a  matter  of 
doubt.  It  is  quite  possible  that  the  same  fibres  may  be  concerned 
in  the  transmission  of  both. 

Diseases  of  the  spinal  cord  in  man  usually  are  widespread  and 
affect  many  tracts ;  the  disorders  of  muscular  paralysis  and  of  sensa- 
tion thus  produced  will  therefore  be  complex.  The  more  limited  the 
lesion,  the  fewer  tracts  will  be  affected,  and  such  conditions  are 
therefore  more  on  all  fours  with  these  localised  lesions  or  sections 
of  tracts  which  can  be  performed  on  animals.  The  operation  of 
hemisection  in  an  animal  produces  paralysis  of  the  same  side  of  the 
body  below  the  injury.  So  it  is  in  a  man  in  whom  disease  has  pro- 
duced an  interruption  of  the  pathways  on  one  side  only  of  the  cord. 
But  such  an  animal  or  man  (and  the  observation  is  more  accurate  in 
man)  will  not  have  lost  all  sensation  on  the  same  side ;  tactile 
discrimination,  and  the  motorial  sense  will  have  largely  disappeared, 
but  sensations  of  pain,  of  heat,  and  of  cold  will  still  remain,  because 
the  tracts  which  convey  such  impulses  cross  over  in  the  cord  at 
varying  levels  after  entering  it,  and  therefore  any  loss  in  such  sensa- 
tions will  occur  on  the  opposite  side  to  that  which  is  injured. 

It  was  no  doubt  absence  of  correct  knowledge  on  this  question 
that  led  Schiff  to  imagine  that  impulses  translated  by  the  brain,  as 
sensations  of  temperature  and  pain,  travelled  up  by  the  grey  matter, 


CH.  XLIX.]  CONDUCTION   IN   THE   CORD  707 

and  not  by  the  posterior  columns.  It  certainly  is  the  case  that  in 
the  condition  called  syringomyelia  (a  disease  of  the  grey  matter  of 
the  cord),  sensations  of  heat,  cold,  and  pain  are  lost,  but  this  is  due 
to  the  disease  cutting  through  the  crossing  fibres  which  convey  the 
impulses  in  question.  Head  has  pointed  out  that  disease  strictly 
limited  to  the  grey  matter  does  not  produce  loss  of  any  kind  of 
sensation,  except  by  interfering  with  those  paths  which  pass  through 
its  substance. 

We  have  seen  that  afferent  impulses  pass  into  the  cord  by 
peripheral  nerves  (the  primary  or  peripheral  level)  in  certain  com- 
binations from  the  protopathic,  epicritic,  and  deep  systems.  In  the 
spinal  cord  these  are  sorted  out  and  travel  up  in  new  combinations, 
and  it  is  possible  that  before  they  finally  reach  the  cortex  a  fresh 
sorting  may  take  place  in  higher  cell-stations  before  they  ultimately 
arrive  at  the  seat  of  consciousness.  The  first  rearrangement  occurs 
at  the  secondary  level,  that  is  on  entrance  into  the  cord,  and  a 
further  sorting  at  the  third  level,  but  of  this  but  comparatively 
little  is  known  at  present.  We  shall  here  only  deal  with  the 
rearrangement  at  the  second  level,  as  derived  from  a  study  of  spinal 
cord  disease. 

We  may  make  a  rough  comparison  of  what  occurs,  to  what  takes 
place  in  the  correspondence  which  flows  in  from  all  quarters  to  a 
busy  man,  such  as  a  Secretary  of  State.  The  letters  will  come  from 
all  quarters,  and  deal  with  numerous  topics ;  some  will  be  private 
letters,  some  will  be  advertisements,  some  will  be  official,  some 
begging  letters,  and  so  forth.  This  mass  of  correspondence  will  be 
sorted  out  by  minor  officials,  the  advertisements  and  the  begging 
letters  will  probably  never  reach  the  busy  officer  of  State,  and  he  will 
therefore  not  be  conscious  of  their  existence  unless  he  examines  the 
waste-paper  basket.  But  the  private  letters  and  the  official  letters 
will  be  sorted  out  into  separate  bags,  whether  they  come  from  England 
or  from  outlying  parts  of  the  Empire,  and  these  ultimately  reach  his 
eye.  In  the  same  way,  the  impulses  that  give  rise  to  pain,  whether 
from  cutaneous  or  deep  structures,  will  all  be  combined  and  travel  up 
one  path.  Those  due  to  heat  or  to  cold,  whether  protopathic  or 
epicritic,  in  other  paths;  those  which  are  tactile  or  motorial,  in 
another.  And  so  a  localised  spinal  lesion  may  interrupt  all  the 
fibres  subserving  the  sensation  of  heat  without  interfering  with  those 
which  underlie  sensations  of  cold,  and  so  forth. 

Tactile,  painful,  and  thermal  impulses,  and  those  associated  with 
tactile  localisation,  cross  in  their  passage  through  the  spinal  cord  at 
varying  levels  soon  after  entrance.  But  the  sensory  impulses  which 
underlie  the  recognition  of  passive  position  and  movement,  and  finer 
tactile  discrimination,  do  not  cross  within  the  limits  of  the  spinal 
cord ;  they  pass  up  the  posterior  column  on  the  side  of  entrance,  and 


708  FUNCTIONS    OF   THE   SPINAL   CORD  [CH.  XL1X. 

so  reach  the  gracile  and  cuneate  nuclei  of  the  bulb,  and  it  is  the 
fibres  which  arise  from  the  cells  of  these  nuclei  which  cross  in  the 
decussation  of  the  fillet. 

The  rapidity  with  which  the  sensory  impulses  cross  to  the 
opposite  side  varies  greatly.  Some,  such  as  those  associated  with 
pain,  heat,  and  cold,  cross  over  in  the  space  of  five  or  six  spinal 
segments.  With  tactile  impulses  the  crossing  is  evidently  less  rapid ; 
but  until  the  crossing  is  completed  there  will  obviously  be  two 
channels,  one  on  each  side  of  the  cord,  open  for  tactile  impulses ; 
and  such  a  double  path  will  be  shorter  for  the  impulses  which  cross 
more  rapidly;  and  finally,  as  just  stated,  the  impulses  associated 
with  position,  movement,  and  tactile  discrimination  have  only  one 
path  in  the  cord,  as  the  decussation  does  not  take  place  until  the 
bulb  is  reached ;  hence  a  hemisection  of  the  cord,  or  of  one  posterior 
column,  will  abolish  these  forms  of  sensibility  from  the  parts  below 
the  lesion,  on  the  same  side  of  the  body  as  the  lesion. 

Painful  impulses  from  the  skin  arriving  in  the  cord  from  proto- 
pathic  fibres  pass  into  the  second  level  at  the  point  of  entry,  and 
rapidly  cross  over  to  the  other  side.  Fibres  of  the  deep  system 
running  with  the  muscular  nerves  and  carrying  impulses  also  of  a 
painful  kind  from  the  same  part  of  the  body  do  not  necessarily  enter 
the  cord  by  the  same  posterior  roots  as  those  carrying  cutaneous 
painful  stimuli.  Thus  more  than  one  segment  of  the  cord  is 
required  before  all  painful  impulses  from  any  one  part  of  the  body 
can  be  gathered  together  and  recombined.  This  is  the  reason  why, 
in  a  local  lesion  in  the  cord,  there  may  be  a  want  of  correspond- 
ence between  the  extent  of  the  cutaneous  and  deep  analgesia  (loss 
of  sensation  to  pain). 

Up  to  this  point  we  have  only  considered  the  sorting  out  of  those 
impulses  which  reach  the  cerebrum  and  thus  rise  into  consciousness. 
In  addition  to  this  there  is  another  group  of  impulses  which  never 
rise  into  consciousness  at  all,  and  although  these  are  afferent  they 
are  therefore  not  sensory. 

Our  previous  illustration  of  the  correspondence  of  a  busy  man 
may  help  us  again  in  understanding  this.  His  clerks  sort  his  letters, 
and  those  of  a  certain  kind  (circulars  and  the  like)  will  probably  never 
reach  him  at  all.  So  it  is  with  afferent  impulses;  the  primary 
sorting  is  into  sensory  and  non-sensory ;  the  sensory  impulses  are 
again  sorted  into  those  of  touch,  pain,  and  temperature;  the  non- 
sensory  impulses  are  those  mainly  destined  for  the  cerebellum,  and 
reach  it  by  the  cerebellar  tracts.  These  travel  up  the  cord  on  the 
side  of  entry,  and  reach  the  same  side  of  the  cerebellum.  This 
explains  the  delay  in  the  crossing  of  the  sensory  impulses  which 
subserve  the  sense  of  position  and  movement  and  tactile  discrimina- 
tion, a  crossing  which,  as  we  have  seen,  does  not  occur  until  the  bulb 


CH.  XLIX.]          REFLEX  ACTION  OF  THE  CORD  709 

is  reached.  It  is  impulses  from  the  joints  and  muscles  which  are 
specially  important  for  the  cerebellum  to  enable  it  to  carry  out  its 
functions  of  equilibration  and  coordination  of  muscular  movements. 
These  impulses  are  non-sensory,  but  they  are  carried  by  fibres  which 
originate  as  collaterals  from  those  which  carry  the  true  sensory 
impulses  of  the  same  nature  to  the  cerebrum.  This  group  of  fibres 
therefore  remains  in  the  cord  on  the  side  of  entry,  in  order  to  be  in 
the  neighbourhood  of  the  cerebellar  tracts ;  the  impulses  reach  the 
cerebellar  tracts  with  the  intermediation  of  a  cell-station  in  Clarke's 
column.  When  the  tract  conveying  what  we  may  term  the  motorial 
sensations  to  the  cerebrum  has  ministered  in  this  way  to  the  needs 
of  the  cerebellum,  there  is  nothing  to  prevent  it  following  the 
example  of  the  other  tracts,  so  when  the  spinal  cord  is  passed  and 
the  bulb  reached,  crossing  of  these  fibres  occurs  in  due  course. 

To  sum  up — the  spinal  cord  is  the  seat  of  the  transmutation  of 
most  of  the  impulses  of  the  first  or  peripheral  level  into  those  of 
the  secondary  level  of  the  afferent  projection  system.  This  recom- 
bination takes  place  on  the  same  side  as  that  by  which  the  impulses 
enter  the  cord.  The  secondary  paths  for  sensory  impulses  then  cross 
with  greater  or  less  rapidity,  so  that  ultimately  all  except  those 
subserving  the  sense  of  position  and  movement  and  tactile  dis- 
crimination have  passed  to  the  opposite  side  within  the  limit  of  the 
spinal  cord  •  and  those  which  do  not  cross  in  the  cord  do  so  after 
reaching  the  nuclei  of  the  posterior  columns.  At  the  same  time, 
within  the  spinal  cord  afferent  impulses  become  separated  into  sensory 
and  non-sensory,  and  the  latter  are  exemplified  by  those  which  reach 
the  same  side  of  the  cerebellum  by  the  cerebellar  tracts. 

Reflex  Action  of  the  Spinal  Cord. 

The  reflex  actions  of  the  spinal  cord  may  first  be  studied  in  the 
brainless  frog.  In  such  a  low  type  of  animal,  the  interdependence  of 
cord  and  brain  is  not  such  a  marked  feature  as  it  is  in  the  higher 
animals,  and  the  spinal  cord  possesses  within  itself  a  great  power  of 
controlling  and  coordinating  very  complex  reflex  actions.  A  study 
of  the  reactions  of  the  frog's  spinal  cord,  moreover,  illustrates  most  of 
the  fundamental  facts  in  relation  to  reflex  action  generally. 

After  destruction  of  the  brain  the  shock  of  the  operation 
renders  the  animal  for  a  variable  time  motionless  and  irresponsive 
to  stimuli,  but  later  on  it  gradually  assumes  a  position  which  differs 
but  little  from  that  of  a  living  conscious  frog.  If  thrown  into 
water  it  will  swim ;  if  placed  on  a  slanting  board  it  will  crawl  up  it 
(Goltz) ;  if  stroked  on  the  flanks  it  will  croak  (Goltz) ;  if  it  is  laid  on 
its  back,  and  a  small  piece  of  blotting-paper  moistened  with  acid  be 
placed  on  the  skin,  it  will  generally  succeed  in  kicking  it  off;  if  a 


710  FUNCTIONS   OF   THE   SPINAL   CORD  [CH.  XL1X. 

foot  is  pinched  it  will  draw  the  foot  away;  if  left  perfectly  quiet  it 
remains  motionless. 

The  muscular  response  that  follows  an  excitation  of  the  surface 
is  purposive  and  constant,  the  path  along  which  the  impulse  is  pro- 
pagated being  definite. 

Under  certain  abnormal  conditions,  however,  the  propagation  of 
the  impulse  in  the  cord  is  widespread,  the  normal  paths  being,  as  it 
were,  broken  down.  This  is  seen  in  the  convulsions  that  occur  on 
slight  excitation  in  animals  or  men  who  have  suffered  from  profuse 
haemorrhage,  or  in  the  disease  called  lockjaw  or  tetanus.  Such  a 
condition  is  easily  demonstrable  in  a  brainless  frog  under  the  influence 
of  strychnine:  after  the  injection  of  a  few  drops  of  a  1  per  cent, 
solution  under  the  skin,  cutaneous  excitation  no  longer  produces  co- 
ordinated responses,  but  paroxysms  of  convulsions,  in  which  the  frog 
assumes  a  characteristic  attitude,  with  arms  flexed  and  legs  extended. 

Spreading  of  reflexes. — If  one  lower  limb  is  excited,  it  is  that  limb 
which  responds :  if  the  excitation  is  a  strong  one  it  will  spread  to  the 
limb  of  the  opposite  side,  and  if  stronger  still,  to  the  upper  limbs  also. 

Pfliiger  taught  that  the  direction  of  irradiation  within  the  spinal 
cord  was  always  upwards.  Sherrington  has  shown  that  this  is  not 
so,  and  has  discovered  many  descending  paths  (see  p.  659). 

Cumulation  of  reflexes. — This  is  well  illustrated  by  Turck's  method. 
If  a  number  of  beakers  of  water  are  prepared,  acidulated  with  1,  2, 
4,  etc.,  parts  of  sulphuric  acid  per  1000,  and  the  tips  of  the  frog's 
toes  are  immersed  in  the  weakest,  the  frog  at  first  takes  no  notice  of 
the  fact,  but  in  time  the  cumulation  or  summation  of  the  sensory 
impulses  causes  the  animal  to  withdraw  its  feet.  If  this  is  repeated 
with  the  stronger  liquids  in  succession,  the  time  that  intervenes  before 
the  muscles  respond  becomes  less  and  less.  This  method  also  serves 
to  test  reflex  irritability  when  the  frog  is  under  the  influence  of 
various  drugs. 

Inhibition  of  reflexes.—  If,  instead  of  the  whole  brain,  the  cerebrum 
only  is  destroyed,  and  the  optic  lobes  are  left  intact,  response  to 
excitation  is  much  slower,  the  influence  of  the  remaining  part  of  the 
brain  inhibiting  the  reflex  action  of  the  cord.  Or  if  in  doing  the 
experiment  with  acid  just  described  the  toes  of  the  other  foot  are 
being  simultaneously  pinched,  the  response  to  the  acid  is  delayed. 

This  influence  of  the  brain  on-  the  cord  is  also  illustrated  in  man, 
by  the  fact  that  a  strong  effort  of  the  will  can  control  many  reflex 
actions.  It  is,  for  instance,  possible  to  subdue  the  tendency  to 
sneeze ;  if  one  accidentally  puts  one's  hand  in  a  flame,  the  natural 
reflex  is  to  withdraw  it :  yet  it  is  well  known  that  Cranmer,  when  being 
burnt  at  the  stake,  held  his  hand  in  the  flames  till  it  was  consumed. 

After  the  spinal  cord  has  been  divided  by  injury  or  disease  in  the 
thoracic  region,  the  brain  can  no  longer  exert  this  controlling  action  ; 


CH.  XL1X.]  REFLEX   ACTION    IN    MAN  711 

hence  the  part  of  the  cord  below  the  injury  having  it,  as  it  were,  all 
its  own  way,  has  its  reflex  irritability  increased.*  The  increase  of 
reflex  irritability  is  also  seen  in  the  disease  called  lateral  sclerosis; 
here  the  lateral  columns,  including  the  pyramidal  tract,  become 
degenerated,  and  so  the  path  from  the  brain  to  the  cells  of  the  cord 
is  in  great  measure  destroyed.  In  these  patients  the  increase  of 
reflex  irritability  may  become  a  very  distressing  symptom,  slight 
excitations,  like  a  movement  of  the  bed-clothes,  arousing  powerful 
convulsive  spasms  of  the  legs. 

Reflex  Action  in  Man. 

The  reflexes  obtainable  in  man  form  a  most  important  factor 
in  diagnosis  of  diseases  of  the  nervous  system ;  each  action  is  effected 
through  an  afferent  sensory  nerve,  a  system  of  nerve-cells  in  the 
cord  termed  the  reflex  centre,  and  an  efferent  motor  nerve;  the 
whole  constitutes  what  is  called  the  reflex  arc.  The  absence  of 
certain  reflexes  may  determine  the  position  in  the  spinal  cord  which 
is  the  seat  of  disease. 

Two  forms  of  reflex  action  must  be  distinguished  :— 

1.  Superficial  reflexes.     These  are  coordinated  reflex  actions,  and 
are  excited  by  stimulation  of  the  skin. 

2.  Deep  reflexes  or  tendon  reflexes. 

Superficial  Reflexes. — These  are  obtained  by  a  gentle  stimula- 
tion, such  as  a  touch  on  the  skin ;  the  muscles  beneath  are  usually 
affected,  but  muscles  at  a  distance  may  be  affected  also.  Thus  a 
prick  near  the  knee  will  cause  a  reflex  flexion  of  the  hip. 

The  most  important  of  these  reflexes  are : 

a.  Plantar  reflex:   withdrawal   of   the  feet  when  the  soles  are 
tickled. 

b.  Grluteal  reflex :  a  contraction  in  the  gluteus  when  the  skin  over 
it  is  stimulated. 

c.  Cremasteric  reflex :  a  retraction  of  the  testicle  when  the  skin  on 
the  inner  side  of  the  thigh  is  stimulated. 

d.  Abdominal    reflex:    a    contraction    of    the    muscles    of    the 
abdominal  wall  when  the   skin    over   the   side  of  the  abdomen  is 
stroked ;  the  upper  part  of  this  reflex  is  a  very  definite  contraction 
at  the  epigastrium,  and  has  been  termed  the  epigastric  reflex. 

e.  A  series  of  similar  reflex  actions  may  be  obtained  in  the  muscles 
of  the  back,  the  highest  being  in  the  muscles  of  the  scapula. 

f.  In  the  region  of  the  cranial  nerves  the  most  important  reflexes 
are  those  of  the  eye — (i)  the  conjunctival  reflex,  the  movement  of  the 

*  In  some  injuries  to  the  cord  produced  by  crushing,  there  is  a  loss  of  reflexes 
below  the  injury!  These,  however,  are  not  simple  transverse  lesions  ;  the  loss  of 
reflex  action  is  due  partly  to  shock,  and  partly  to  extensive  injury  of  the  grey  matter. 


712 


FUNCTIONS   OF  THE   SPINAL   COKD 


[CH.  XLIX. 


FIG.  440.— The  Knee-jerk.    (Gowers.) 


eyelids  when  the  front  of  the  eyeball  is  touched ;  and  (ii)  the  con- 
traction of  the  pupil  on  exposure  of  the  eye  to  light,  and  its  dilatation 
on  stimulation  of  the  skin  of  the  neck. 

Tendon  Reflexes. — When  the  muscles  are  in  a  state  of  slight 
tension,  a  tap  on  their  tendons  will  cause  them  to  contract.     The 

tendon  reflexes  which  are 
generally  examined  are  the 
patella  tendon  reflex  or  knee- 
jerk,  the  tendo  Achillis  reflex 
or  ankle-jerk,  and  phenomenon 
known  as  ankle-clonus. 

The  knee-jerk. — The  quad- 
riceps muscle  is  slightly 
stretched  by  putting  one  knee 
over  the  other;  a  slight  blow 
on  the  patella  tendon  causes  a 
movement  of  the  foot  for- 
wards, as  indicated  in  the 
dotted  line  of  fig.  440.  The 
phenomenon  is  present  in 
health. 

The  ankle-jerk  is  one  of 
great  importance,  for  in  such 

diseases  as  locomotor  ataxy,  in  which  the  tendon  reflexes  are  lost,  it 

usually  disappears  before  the  knee-jerk.     It  is  best  elicited  if  the 

patient  kneels   with   one  knee 

upon  a  cushioned  chair,  whilst 

standing  on  the  other  leg  by  the 

side   of   the    chair.      The    calf 

muscles  of  the  kneeling  leg  are 

thus  relaxed,  and  a  sharp   tap 

upon  the  tendo  Achillis  elicits 

the  jerk. 

Ankle-clonus.  —  This  is   eli- 
cited as  depicted  in   the   next 

figure:     the    hand    is    pressed 

against  the  sole  of  the  foot,  the 

calf  muscles  are  thus  put  on  the 

stretch  and  they  contract,  and 

if  the   pressure   is   kept  up  a 

quick  succession  or  clonic  series 

of  contractions  is  obtained.     This,  however,  is  not  readily  obtained 

in  health. 

The  phenomena  depend  for  their  occurrence  on  the  integrity  of 

the  reflex  arc.     Disease   or   injury  to   the   afferent   nerve,  efferent 


FIG.  441. — Ankle-clonus.    (Gowers.) 


CH.  XLIX.]  REFLEX  ACTION   IN   MAN  713 

nerve,  or  spinal  grey  matter,  abolishes  them.  Thus  they  cannot  be 
obtained  in  locomotor  ataxy  (damage  to  the  posterior  nerve-roots), 
or  in  infantile  paralysis  (damage  to  the  anterior  horns  of  grey 
matter). 

They  are  excessive  in  those  conditions  which  increase  reflex 
irritability,  such  as  severance  of  brain  from  cord,  and  in  lateral 
sclerosis,  that  is,  a  degenerative  condition  of  the  pyramidal  tract. 

In  order  that  the  muscle  may  respond,  it  is  necessary  that  it 
be  in  an  irritable  condition;  this  is  accomplished  by  putting  it 
slightly  on  the  stretch,  and  so  calling  forth  the  condition  called  tonus, 
and  thus  a  readiness  to  contract  on  slight  provocation.  Until  the 
last  few  years,  considerable  doubt  existed  as  to  whether  the  tendon- 
reflexes  were  true  reflex  actions,  because  it  was  asserted  that  the 
time  intervening  between  the  stimulus  and  the  muscular  response 
was  too  short.  Now  that  we  know  that  nerve-impulses  are  in  man 
propagated  at  the  rate  of  120  metres  per  second  (and  not  at  the  rate 
of  30  metres  per  second  as  was  formerly  supposed),  this  difficulty 
has  disappeared.  Jolly  has  made  careful  time  measurements,  and 
demonstrated  that  in  the  knee-jerk  there  is  sufficient  time  for  the 
nerve  impulse  to  travel  to  the  spinal  cord  and  back  again,  but  that 
the  time  occupied  in  the  cord  itself  is  only  about  half  that  which  is 
necessary  in  the  case  of  ordinary  coordinated  reflex  actions.  This  is 
explicable  on  the  assumption  that  the  tendon  reflexes  are  subserved 
by  the  collaterals  of  the  entering  afferent  fibres  which  go  direct  to 
the  anterior  horn  cells,  whereas  ordinary  reflexes  are  worked  through 
intermediate  neurons,  and  therefore  have  to  pass  through  additional 
synapses. 

The  increased  rapidity  of  a  tendon  reflex  is  useful,  for  a  sudden 
strain  on  a  ligament  would  rupture  some  of  its  fibres  or  lead  to 
injury  of  the  joint  surfaces  if  too  great  a  time  intervened  before  the 
muscles  could  contract  and  so  save  the  joint. 

The  exact  course  of  the  reflex  arc  concerned  in  the  knee-jerk  has 
been  worked  out  by  Sherrington  in  the  monkey.  The  nerve-fibres 
are  mainly  those  which  pass  (1)  to  and  from  the  crureus  by  the 
anterior  crural  nerve,  and  (2)  to  and  from  the  hamstrings  by  the 
sciatic  nerve.  The  fibres  which  supply  the  crureus  arise  from  the 
spinal  nerve-roots  which  in  man  correspond  to  the  3rd  and  4th 
lumbar ;  the  hamstring  supply  is  from  the  5th  lumbar  and  1st  and 
2nd  sacral  roots. 

Lombard's  experiments  upon  the  knee-jerk  indicate  that  it  is 
sometimes  more  readily  obtained  even  in  the  same  person  than  at 
other  times.  It  varies  with  changes  in  mental  activity,  and  during 
sleep  may  be  entirely  absent.  It  is  increased  and  diminished  by 
whatever  increases  or  diminishes  the  relative  state  of  irritability  of 
the  nervous  system  as  a  whole. 


714  FUNCTIONS   OF   THE   SPINAL   CORD  [CIL  XL1X. 

Closely  related  to  this  is  the  phenomenon  known  as  reinforcement 
of  the  knee-jerk,  which  was  first  described  by  Jendrassik  in  1883,  and 
has  since  been  studied  by  numerous  observers.  The  extent  of  the 
jerk  may  be  increased  if  at  the  time  the  patella  tendon  is  struck,  a 
strong  voluntary  contraction,  such  as  clenching  the  fists  or  the  jaw, 
is  made  by  the  individual.  In  many  normal  persons  the  knee-jerk 
is  difficult  to  elicit,  but  in  these  it  may  usually  be  obtained  by  the 
reinforcing  action  just  described. 

After  the  reinforcing  action  has  occurred  it  is  followed  by  an 
interval  in  which  the  knee-jerk  is  lessened  (inhibition  or  negative 
reinforcement).  Many  explanations  have  been  offered  of  the 
phenomenon ;  one  is  the  "  overflow  "  theory,  that  is,  motor  impulses 
from  the  brain  which  produce  a  contraction  of  hands  or  jaw  will  not 
only  affect  the  lower  centres  concerned  in  such  movements,  but  will 
also  overflow  to  other  regions,  for  instance,  those  which  come  into 
play  in  the  knee-jerk  and  influence  motor  irritability  there.  The 
"  drainage "  theory  of  M'Dougall  to  be  described  a  few  paragraphs 
ahead  may  possibly  explain  reinforcement ;  the  drainage  of  nervous 
potential  to  one  part  will  lessen  the  resistance  of  the  synaptic 
junctions  and  cause  a  drainage  of  nervous  energy  from  other  parts, 
and  so  allow  reflex  actions  to  be  more  readily  elicited  there. 

We  have  devoted  most  space  to  the  knee-jerk  because  this  tendon  reflex  is  the 
one  which  has  been  longest  known  and  most  worked  at.  The  recent  investiga- 
tions of  Babinski  have,  however,  shown  that  other  tendon  phenomena  may  be 
quite  as  easily  investigated,  and  in  some  cases  are  more  valuable  aids  to  diagnosis 
than  the  knee-jerk.  Amongst  these  we  have  already  referred  to  the  ankle-jerk. 
Another  phenomenon  allied  to  these  is  usually  called  UabinskVs  sign,  or  the  extensor 
plantar  reflex.  If  the  sole  of  the  foot  is  stroked,  the  usual  response  is  flexion  of 
the  toes,  and  especially  of  the  big  toe.  If  the  pyramidal  tract  is  diseased,  extension 
of  the  great  toe  occurs.  This  is  a  very  delicate  reaction,  and  occurs  long  before 
any  exaggeration  of  the  knee-jerk  takes  place.  In  new-born  children  the  normal 
response  is  not  obtained  because  their  pyramidal  tracts  are  not  then  fully  developed. 
The  weakness  of  the  test,  however,  is  that  in  many  people  it  is  difficult  to  elicit 
the  reflex,  and  minor  conditions  such  as  cold  feet  interfere  with  it. 

Among  numerous  other  reactions  there  is  one  which  Hertz  proposes  to  call 
BabinskVs  second  sign  ;  it  is  this.  If  a  normal  person  lies  down  with  the  legs  widely 
separated  and  the  arms  folded,  and  tries  to  sit  up,  both  legs  rise  from  the  ground 
to  an  equal  extent.  On  letting  himself  fall  back  sharply  both  legs  again  rise 
equally  from  the  ground.  In  hemiplegia  due  to  organic  disease,  as  soon  as  the 
patient  is  strong  enough  to  make  such  an  effort,  the  paralysed  leg  rises  higher  than 
the  healthy  limb.  In  hysterical  hemiplegia,  which  often  simulates  the  genuine 
disease,  the  paralysed  leg  remains  flat  on  the  ground,  both  on  sitting  up  or  lying 
down,  as  this  is  what  an  uninitiated  person  would  expect.  This  has  been  found  of 
much  service  in  distinguishing  the  two  conditions. 

Reciprocal  Action  of  Antagonistic  Muscles. — This  is  an 
interesting  branch  of  muscle  physiology,  which  we  owe  to  the 
researches  of  Sherrington.  In  brief,  he  shows  that  the  inhibition 
of  the  tonus  of  a  voluntary  muscle  may  be  brought  about  by 
excitation  of  its  antagonist. 


CH.  XLIX.]  ANTAGONISTIC   MUSCLES  715 

Movement  at  a  joint  in  any  direction  involves  the  shortening 
of  one  set  of  muscles  and  the  elongation  of  another  (antagonistic) 
set.  The  stretching  of  a  muscle  produced  by  the  contraction  of 
its  antagonist  mechanically  stimulates  the  sensory  nerve-endings 
in  the  muscle  -  spindles  of  the  muscle  that  is  under  exten- 
sion; in  this  way  a  reflex  of  pure  muscular  initiation  may  be 
started.  Experiments  show  that  electrical  excitation  of  the 
central  end  of  an  exclusively  muscular  nerve  produces  inhibition 
of  the  tonus  of  its  antagonist.  For  instance,  the  central  end  of  the 
severed  hamstring  nerve  is  faradised.  This  nerve  contains  in  the 
cat  4510  nerve-fibres,  and  of  these  about  1810  are  sensory  in 
function ;  *  these  come  from  the  flexor  muscles  of  the  knee,  not 
from  the  skin.  The  effect  of  the  stimulation  of  the  nerve  on  the 
tonus  of  the  extensor  muscles  of  the  knee  is  seen  (a)  in  elongation 
of  those  muscles,  (b)  in  temporary  diminution  of  the  knee-jerk. 
The  experiment  may  be  varied  as  follows :  the  exposed  flexor 
muscles  detached  from  the  knee,  and  therefore  incapable  of 
mechanically  affecting  the  position  of  the  joint,  are  stretched  or 
kneaded.  This  produces  a  reflex  elongation  of  the  extensor  muscles 
of  the  knee  and  a  temporary  diminution  of  the  knee-jerk.  The 
effects  are  in  fact  the  same  as  those  produced  by  faradisation  of  the 
central  end  of  the  nerve  supplying  them.  It  may  therefore  be  that 
reciprocal  innervation,  which  is  a  common  form  of  coordination  of 
antagonistic  muscles,  is  secured  by  a  simple  reflex  mechanism,  an 
important  factor  in  its  execution  being  the  tendency  for  the  action  of 
a  muscle  to  produce  its  own  inhibition  reflexly  by  mechanical  stimu- 
lation of  the  sensory  apparatus  in  its  antagonist. 

We  have  in  our  description  of  the  anatomical  path  of  the  entering 
posterior  roots  drawn  attention  to  what  may  be  termed  the  three 
"  nervous  circles  "  by  which  an  afferent  impulse  may  affect  the  motor 
discharge  from  the  anterior  horn-cells  of  the  cord ;  there  is  the  short 
path  by  the  collaterals  of  the  entering  fibre  which  pass  directly  to 
these  cells,  and  there  are  the  two  longer  paths,  via  the  cerebellum 
and  cerebrum  respectively.  In  the  execution  of  a  voluntary  action 
all  three  circles  are  in  activity  to  produce  the  coordination  and  due 
contraction  and  elongation  of  antagonistic  muscles  which  characterise 
an  effective  muscular  act.  Section  of  the  posterior  roots  produces 
not  only  an  inability  to  carry  out  reflex  actions,  but  also  leads  to  an 
inability  to  carry  out  effectively  those  more  complicated  reflex  actions 
which  are  called  voluntary,  and  in  which  the  brain  participates. 
Locomotor  ataxy,  or  tabes  dorsalis,  is  a  slowly  progressive  disease, 
the  anatomical  basis  of  which  is  a  degeneration  of  the  nerve-units  of 
tho  spinal  ganglia.  It  is,  therefore,  analogous  to  a  physiological 

*  The  number  of  sensory  nerve-fibres  is  determined  by  counting  the  healthy 
fibres  in  the  nerve  after  section  of  the  anterior  nerve-roots. 


716 


FUNCTIONS   OF  THE  SPINAL  COED 


[CH.  XL1X. 


experiment  in  which  the  posterior  roots  are  divided,  and  although 
some  fibres  may  remain  which  still  allow  of  the  passage  of  nervous 
impulses,  the  action  of  the  three  circles  is  greatly  interfered  with ; 
the  spinal  reflex  arc  is  at  fault ;  this  is  shown  by  the  loss  of  reflex 
action,  the  disappearance  of  the  tendon  reflexes,  and  the  want  of 
tonus  in  antagonistic  muscles ;  the  main  symptom  of  the  disease  is 
want  of  muscular  coordination,  and  this  is  produced  not  only  by  the 
lesion  in  the  spinal  cord,  but  is  accentuated  by  the  want  of  continuity 
in  the  other  two  circles,  so  that  the  brain  is  unable  to  effectively 
control  the  motor  discharge  from  the  anterior  cornual  cells. 

M'DougalVs  "Drainage"  theory.— This  theory  is  an  attempt  to  explain  the 
reciprocal  action  of  antagonistic  muscles. 

The  accompanying  diagram  represents  two  antagonistic  muscles  (fig.  442)  with 


FLEXOR 


EXTENSOR 


Fio.  442.— Diagram  to  illustrate  M'Dougall's  "Drainage"  theory. 


their  nerve  supplies.  Each  is  in  connection  with  a  reflex  arc  shown  in  a  simple 
schematic  way,  as  consisting  of  three  neurons,  A15  A2,  A3,  and  Blf  B2,  and  B3 
respectively. 

A!  and  Bx  are  the  afferent  neurons  ; 

A2  and  B2  are  the  association  or  internuncial  neurons  within  the  central  nervous 
system. 

A3  and  B3  are  the  efferent  or  motor  neurons. 

When  a  stimulus  is  applied  to  Al  it  generates  nervous  energy,  and  discharges 
across  the  synapse  to  A2,  and  finally  to  A3,  and  the  muscle  contracts.  The  problem 
then  is  to  imagine  such  a  mode  of  connection  between  arc  A  and  arc  B  as  will 
cause  arc  A  during  activity  to  drain  off  from  arc  B  the  smaller  amount  of  nerve 
energy  in  it  which  normally  keeps  the  muscle  supplied  by  B3  in  a  state  of  tonus  ; 
if  this  is  done,  the  muscle  of  arc  B  will  lose  its  tonicity  and  become  relaxed. 
It  is  probable  that  this  connection  is  by  means  of  a  collateral  of  the  internuncial 
neuron  B2  crossing,  as  shown  in  the  figure  and  taking  part  with  the  axon  of  A2  in 
the  formation  of  the  synapse  with  A3.  The  normal  resistance  of  this  synapse  is 
lowered  by  the  stimulation  applied  to  the  arc  A,  and  this  lowering  of  resistance  is 
participated  in  by  the  part  of  the  synapse  to  which  the  crossing  collateral  from  B2 
contributes  ;  owing  to  this  lowering  of  resistance,  nervous  energy  therefore  drains 
over  from  the  arc  B,  and  so  the  muscle  it  supplies  is  relaxed. 

The  theory  may  also  be  applied  to  explain  (1)  alternating  reflexes,  as  described 
under  our  description  of  the  scratch  reflex  (p.  712) ;  (2)  the  reinforcement  of  the 
knee-jerk  and  other  phenomena  in  which  reflex  arcs  are  concerned  (p.  708) ;  and 
(3)  certain  psychological  phenomena  such  as  attention. 

The  Principle  of  the  Common  Path  (Sherrington). — When  an 
afferent  nerve  is  stimulated,  the  impulse  enters  that  complex  network 


CH.  XLIX.]  THE  COMMON   PATH  717 

of  conducting  paths,  which  is  called  the  central  nervous  system.  So 
numerous  are  the  potential  connections  in  this  labyrinth  that  the 
impulse  may,  under  such  abnormal  conditions  as  strychnine  poison- 
ing, radiate  in  all  directions,  and  be  discharged  so  as  to  throw  all  the 
muscles  of  the  body  into  action.  But  under  normal  circumstances 
the  irradiation  is  limited  to  certain  lines,  which  increase  in  number 
with  the  strength  of  the  entering  impulse.  The  general  pattern  of 
the  nervous  web  remains  fairly  constant,  but  its  details  are  subject 
to  great  variations,  and  a  new  stimulus  may  act  like  a  tap  on  a 
kaleidoscope,  and  throw  a  new  pattern  into  being. 

At  the  commencement  of  every  reflex  arc  is  a  receptive  neuron 
extending  from  a  sensory  surface  to  the  brain  or  cord,  and  this  is  a 
private  path  exclusively  occupied  by  impulses  from  its  own  receptive 
points  on  the  surface  of  the  body.  These  impulses  pass  along 
certain  association  tracts  or  internuncial  paths  in  the  central  nervous 
system,  and  at  the  termination  of  the  arc  we  have  a  final  neuron 
which  acts  as  the  conducting  link  between  the  central  nervous 
system  and  the  muscle  or  gland  which  it  supplies.  This  final  neuron 
does  not  subserve  exclusively  impulses  generated  at  one  receptive 
source,  but  can  be  used  in  the  conduction  of  impulses  generated  at 
many  points  of  the  body's  surface.  The  arm  muscles,  for  instance, 
can  be  thrown  into  play  in  response  to  visual,  auditory,  tactile,  and 
other  sensations.  The  final  neuron  thus  differs  from  the  initial 
neuron  in  being  public,  not  private,  and  may  be  spoken  of  as  the 
final  common  path.  Of  course,  in  every  reflex  action  we  are  not 
really  concerned  with  individual  neurons,  but  with  thousands  of 
them  acting  in  harmony ;  still,  for  descriptive  purposes,  it  is  well  to 
speak  of  one  set  of  neurons  only  as  a  sample  of  the  rest.  An  ordinary 
motor  nerve  is  thus  a  collection  of  many  final  common  paths. 

Now  let  us  suppose  that  two  stimuli  are  acting  on  different  parts 
of  the  body's  surface,  each  of  which  would  produce  impulses  that 
ultimately  reach  the  same  final  common  path  together,  though  they 
may  throw  the  motor  organ  into  action  in  rather  a  different  way. 
Under  such  circumstances,  it  is  found  that  the  occupation  of  the 
public  path  by  one  impulse  prevents  it  being  simultaneously  used  by 
the  other ;  one  reflex  or  the  other  takes  place,  but  not  both  of  them. 

For  the  investigation  of  such  a  problem,  the  "  scratch  reflex  "  of 
the  dog  is  one  that  lends  itself  admirably.  This  can  best  be  studied 
in  the  "  spinal "  dog,  that  is  in  a  dog  in  which  cerebral  influence  is 
shut  off  by  division  of  the  spinal  cord  in  the  lower  cervical  region.  If 
the  skin  over  a  large  saddle-shaped  area  covering  the  shoulders  and 
back  is  gently  irritated  on  one  side,  the  hind  leg  of  the  same  side 
executes  scratching  movements,  which  involve  flexor  muscles  princi- 
pally ;  the  rate  of  scratching  is  about  4  per  second,  and  each  move- 
ment is  presumably  a  short  tetanus.  The  best  "artificial  flea"  to 


718 


FUNCTIONS   OF   THE   SPINAL   CORD 


[CH.  XLIX. 


employ  is  a  weak  faradic  current,  and  ifc  is  the  nerves  at  the  roots 
of  the  hair  follicles  which  are  specially  susceptible  when  eliciting 


FIG.  443. — The  Scratch  reflex.  Tracing  of  the  flexors  of  left  hip  evoked  by  stimulation  of  the  skin 
of  the  shoulder.  The  depression  in  the  signal  line  S  indicates  the  commencement  of  the  stimulation, 
and  its  rise  the  termination.  While  this  was  going  on,  the  left  foot  was  stimulated,  and  the 
depression  of  the  signal  line  L  indicates  the  duration  of  this  stimulation ;  during  the  stimulation 
of  the  foot,  and  for  a  short  time  afterwards,  the  scratch  reflex  is  inhibited,  but  the  scratch  reflex 
returns  soon  afterwards.  The  time  is  registered  in  fifths  of  seconds.  To  be  read  from  left  to 
right.  (Sherrington.) 

the  reflex.  The  internuncial  paths  in  the  cord  are  in  the  lateral 
part  of  the  lateral  column,  and  division  of  that  region  of  the  cord 
abolishes  the  reflex. 


CH.  XLIX.j  THE  SCRATCH   REFLEX  719 

But  there  is  another  form  of  stimulation  which  also  throws 
the  same  flexor  muscles  into  action,  although  in  rather  a  different 
way,  and  that  is  stimulation  of  the  sole  of  the  foot.  The  foot 
and  leg  are  withdrawn,  and  the  action  is  a  steady  one,  and  not 
a  succession  of  rhythmic  discharges  as  in  scratching.  Both  reflexes, 
however,  end  in  the  same  final  common  path ;  and  if  while  scratch- 
ing is  being  elicited  by  stimulation  of  the  shoulder,  the  foot  is  then 
stimulated  simultaneously,  scratching  immediately  ceases;  one  set 
of  impulses  has  displaced  the  other  from  the  final  common  path. 
If  then  one  ceases  to  stimulate  the  foot,  the  scratch  reflex  returns  if 
the  irritation  of  the  shoulder  is  kept  up.  This  is  well  illustrated  by 
the  tracing  (fig.  443). 

But  there  is  also  another  way  in  which  the  inhibition  of  reflexes 
may  be  produced.  The  contraction  of  one  set  of  muscles  is  usually 
accompanied  by  relaxation  of  its  antagonists,  and  the  contraction  of 
the  flexors  in  the  scratch  reflex  may  therefore  be  inhibited  by  making 
the  antagonistic  muscles  (the  extensors)  contract.  Further,  the 
scratch  reflex  is  unilateral,  but  this  does  not  mean  that  the  muscles 
supplying  the  other  legs  are  inactive,  for  they  must  act  in  such  a 
way  as  to  support  the  dog  on  three  legs,  while  it  scratches  with  the 
fourth.  So  if  the  right  shoulder  is  stimulated,  the  right  hind  leg 
scratches ;  if  the  left  shoulder  is  stimulated,  the  left  hind  leg 
scratches ;  but  if  both  shoulders  are  stimulated  together,  only  one  or 
the  other  leg  scratches,  not  the  two  at  once ;  parts  of  the  final  paths 
are  common  to  both  sides,  and  there  is  a  struggle  for  their  occupa- 
tion. Some  instances  of  reinforcing  action  were  found ;  for  example, 
if  two  points  of  the  skin  of  one  shoulder  are  stimulated  with  a  very 
feeble  current,  neither  stimulus  alone  may  be  sufficient  to  evoke 
the  scratch  reflex,  but  the  two  together  may  elicit  it;  in  order 
to  attain  this  result  the  two  points  of  skin  must  be  fairly  close 
together. 

The  afferent  neurons  (private  paths)  of  the  body  are  about  five 
times  more  numerous  than  the  efferent  (final  common  paths),  and  in 
the  struggle  for  the  occupation  of  these  public  paths  by  the  impulses 
that  enter  the  central  nervous  system  by  the  more  numerous 
private  paths,  three  factors  are  specially  concerned : — (1)  Strength  of 
stimulus ;  the  stronger  the  stimulus  the  better  chance  the  resulting 
impulse  has  of  getting  round  to  the  motor  organ.  (2)  Character  of 
impulse;  sensations  of  painful  nature  and  sexual  feelings  win  the 
final  path  easily;  it  is  a  matter  of  common  experience  that  such 
sensations  dominate  and  even  exclude  other  sensations ;  a  man  with 
bad  toothache  is  not  likely  to  take  much  notice  of  anyone  who  pulls 
his  coat  tails.  (3)  Fatigue;  at  the  end  of  a  long  stimulation,  a 
stimulus  applied  to  a  fresh  reflex  arc  has  a  better  chance  of  capturing 
the  common  path. 


720 


FUNCTIONS   OF  THE   SPINAL  CORD 


[CH.  XLIX, 


Reaction  Time  in  Man. — The  term  reaction  time  is  applied  to  the  time  occu- 
pied in  the  central  nervous  system  in  that  complex  response  to  a  pre-arranged 
stimulus  in  which  the  brain  as  well  as  the  cord  comes  into  play.  It  is  sometimes 
called  the  personal  equation.  It  may  be  most  readily  measured  by  the  electrical 
method,  and  the  accompanying  diagram  (fig.  444)  will  illustrate  one  of  the  numerous 
arrangements  which  have  been  proposed  for  the  purpose. 

In  the  primary  circuit  two  keys  (A  and  B)  are  included,  and  a  chronograph  (1), 
arranged  to  write  on  a  revolving  cylinder  (fast  rate).  Another  chronograph  (2), 


FIG.  444.— Reaction  time. 

marking  l-100ths  of  a  second,  is  placed  below  this.  The  experiment  is  performed 
by  two  persons  C  and  D.  The  key  A,  under  the  control  of  C,  is  opened.  The  key 
B,  under  the  control  of  D,  is  closed.  The  electrodes  E  are  applied  to  some  part  of 
D's  body.  C  closes  A.  The  primary  circuit  is  made,  and  the  chronograph  moves. 
As  soon  as  D  feels  the  shock  he  opens  J3,  the  current  is  thus  broken,  and  the 
chronograph  lever  returns  to  rest.  The  time  between  the  two  movements  of  the 
chronograph  (1)  is  measured  by  means  of  the  time-tracing  written  by  chronograph 
(2).  From  this,  the  time  occupied  by  transmission  along  the  nerves  has  to  be 
deducted,  and  the  remainder  is  the  reaction  time.  It  usually  varies  from  0'15  to  0*2 
second,  but  is  increased  in  : — 

The  Dilemma. — The  primary  circuit  is  arranged  as  before.  The  wires  from 
the  secondary  coil  lead  to  the  middle  screws  of  a  reverser  without  cross  wires.  To 
each  pair  of  end  screws,  a  pair  of  electrodes  E  and  E'  pass ;  these  are  applied  to 
different  parts  of  D's  body  (fig.  445).  It  is  arranged  previously  that  D  is  to  open 
B,  when  one  part  is  stimulated,  but  not  the  other,  C  adjusting  the  reverser  unknown 
to  D,.  Under  these  circumstances  the  reaction  time  is  longer. 

The  reaction  time  in  response  to  various  kinds  of  stimuli,  sound,  light,  pain, 
etc.,  varies  a  good  deal;  the  condition  of  the  subject  of  the  experiment  is  also  an 


FIG.  445.— The  Dilemma. 


important  factor.     This,  however,  is  really  a  practical  branch  of  psychology,  and 
has  recently  been  much  worked  at  by  students  of  that  science  (see  also  p.  lyi). 


CH.  XLIX.]  VISCERAL  REFLEXES  721 


Spinal  Visceral  Reflexes. 

The  spinal  grey  matter  contains  centres  which  regulate  the 
operation  of  many  involuntary  muscles.  Some  of  these  centres  are  : — 

The  cilio-spinal  centre  controls  the  dilatation  of  the  pupil ;  it  is 
situated  in  the  lower  cervical  region,  reaching  as  far  down  as  the 
origin  of  the  first  to  the  third  thoracic  nerve. 

Subsidiary  vaso-motor  centres.  The  principal  vaso-motor  centre 
is  situated  in  the  bulb,  and  subsidiary  centres  are  scattered  through 
the  spinal  grey  matter  (see  p.  302). 

The  same  is  probably  true  for  all  the  muscular  viscera,  but 
particular  study  has  been  directed  to  those  in  the  pelvis,  and  centres 
for  micturition,  defcecation,  erection,  and  parturition  are  contained  in 
the  lumbo-sacral  region  of  the  cord.  If  the  spinal  cord  is  cut  through 
above  the  situation  of  these  centres,  the  result  is  in  general  terms 
that  any  influence  of  the  higher  (voluntary)  centres  over  these 
actions  is  no  longer  possible.  The  actions  in  question  are  then 
simply  reflex  ones  occurring  unconsciously  at  certain  intervals,  and 
set  in  movement  by  the  peripheral  stimulus  (fulness  of  bladder,  or  of 
rectum,  etc.).  If  the  portion  of  the  cord  where  these  centres  are 
placed  is  entirely  destroyed,  the  result  is  paralysis  of  the  muscles 
concerned,  though  in  certain  cases,  even  after  such  a  severe  injury, 
some  amount  of  recovery  has  been  noticed,  which  must  be  attributed 
to  the  peripheral  ganglia  being  able  to  play  the  part  of  reflex  centres. 

The  phenomena  of  micturition  (p.  580),  and  defaecation  (p.  562) 
have,  however,  already  been  described  at  length,  arid  it  only  remains 
to  add  a  few  words  concerning  two  other  reflexes  in  which  the 
generative  organs  are  concerned. 

Uterine  Reflexes. — Uterine  contractions  can  be  induced  by  rectal  injections, 
the  passage  of  a  foreign  body  into  the  uterus,  the  application  of  the  child  to  the 
breast,  and  by  other  means.  In  animals  faradisation  of  the  central  end  of  the  first 
sacral  nerve  produces  the  same  result.  The  contractions  of  the  uterus  are  therefore 
reflex.  Several  cases  have  been  recorded  in  which  parturition  has  occurred  normally 
in  women  who  have  had  the  cord  divided  across  completely  in  the  thoracic  region  ; 
it  is  thus  evident  the  centre  must  be  a  lumbar  one.  In  such  cases  the  uterine  con- 
tractions technically  called  " pains"  are  strong,  but  pain  is,  of  course,  absent.  The 
communication  with  the  lumbar  region  appears  to  be  principally  by  the  first  three 
lumbar  nerves.  Similar  observations  have  been  made  experimentally  in  animals,  and 
in  one  of  Goltz  and  Ewald's  dogs  in  which  the  cord  had  been  removed  from  the  lower 
thoracic  region  downwards,  pregnancy  followed  coitus,  and  terminated  with  success- 
ful parturition.  The  mammary  glands  enlarge  as  usual  in  such  cases,  even  when,  as 
iq  Routh's  well-known  case  (where  the  cord  was  completely  destroyed  at  the  seventh 
thoracic  segment),  there  can  be  no  nervous  communication  between  the  pelvis  and 
the  breast. 

Erection. — This  can  be  excited  in  man  even  immediately  after  a  transverse 
lesion  of  the  cord ;  so  also  can  ejaculation,  but  not  so  commonly.  The  evidence 
in  favour  of  such  acts  being  spinal  reflexes  is  very  complete  in  the  case  of  animals. 


2  Z 


OHAPTEK  L 

FUNCTIONS  OF  THE  CEREBRUM 

THE  cerebrum  is  the  seat  of  those  psychical  or  mental  processes 
which  are  called  volition  and  feeling ;  volition  is  the  starting-point 
in  motor  activity;  feeling  or  consciousness  is  the  final  phase  of 
sensory  impressions ;  the  correlation  of  sensations  with  one  another, 
and  with  volitional  impulses  so  generated  is  what  constitutes 
thought.  That  the  brain  is  the  organ  (or  anatomical  correlate)  of 
mind  is  to-day  a  matter  of  such  common  knowledge  that  it  is 
almost  superfluous  to  mention  it  in  a  physiological  text-book.  Yet 
its  functions  were  entirely  unknown  or  only  dimly  conjectured  by 
ancient  philosophers,  and  the  overwhelming  importance  of  the  grey 
matter  on  its  surface  in  mental  phenomena  is  a  discovery  of  com- 
paratively recent  date. 

Effects  of  Removal  of  the  Cerebrum. 

The  functions  of  any  organ  may  be  discovered  (in  part,  at  any 
rate)  by  removing  it ;  and  the  brainless  frog  which  we  have  studied 
in  relation  to  the  functions  of  the  spinal  cord  is  also  a  useful  object- 
lesson  to  teach  us  the  uses  of  the  part  removed,  by  observing  in 
what  manner  the  animal  differs  from  one  which  has  its  brain  intact. 
If,  instead  of  taking  a  frog,  we  take  an  animal  lower  in  the  scale, 
where  the  brain  is  not  so  fully  developed,  the  effect  of  removing  that 
organ  will  be  less  marked ;  or  if  we  remove  the  brain  in  a  more 
highly  developed  animal,  the  simultaneous  removal  of  the  brain 
functions  will  be  naturally  more  noticeable.  We  have  already  seen 
(Chapter  XLIV.)  that  the  development  of  the  cerebral  hemispheres 
increases  in  importance  as  we  rise  in  the  animal  scale. 

If  the  cerebral  hemispheres  are  removed  in  a  teleostean  or  bony 
fish  (and  in  such  animals  there  is  only  a  rudimentary  cortex),  the 
animal  is  to  all  intents  and  purposes  unaffected ;  it  can  distinguish 
between  a  worm  and  a  piece  of  string,  and  will  rise  to  red  wafers  in 
preference  to  those  of  another  colour.  The  operation  does  not 

722 


CH.  L.]  REMOVAL  OF  THE  CEREBRUM  723 

damage  the  primary  centres  of  vision  (the  optic  lobes,  which  corre- 
spond to  the  corpora  quadrigemina  of  the  mammal),  and  in  these 
fishes  the  eye  is  the  most  important  sense  organ. 

A  shark,  however,  subjected  to  the  same  operation,  is  reduced  to 
a  condition  of  complete  quiescence ;  this  is  due  to  the  circumstance 
that  in  this  fish  the  principal  sense  organ  is  that  of  smell,  and  sever- 
ance of  both  olfactory  tracts  produces  the  same  result  as  removal 
of  the  entire  cerebrum.  In  either  case  the  path  between  the 
olfactory  bulbs  and  the  centres  that  control  the  cord  are  interrupted. 

Going  higher  in  the  animal  scale  to  the  frog,  we  find  that  re- 
moval of  the  hemispheres  only  does  not  entirely  abolish  it's  apparent 
spontaneity;  it  still  continues  to  feed  itself,  for  instance,  by  catching 
passing  insects.  It  is  not  until  the  optic  thalami  are  removed  also 
that  it  becomes  the  purely  reflex  animal  described  on  p.  709.  If 
the  brain  and  the  anterior  end  of  the  bulb  are  removed  the  lower 
centres  of  the  cord  are  set  free,  and  the  result  is  incessant  movement 
provoked  by  slight  stimuli. 

A  bird  treated  in  the  same  way  remains  perfectly  motionless, 
sleepy,  and  unconscious,  unless  it  is  disturbed  (see  fig.  446).  When 


FIG.  446. — Pigeon  after  removal  of  the  hemispheres.    (Dalton.) 

disturbed  in  any  way  it  will  move ;  for  instance,  when  thrown  into 
the  air  it  will  fly ;  but  these  movements  are,  as  in  the  frog,  purely 
reflex  in  character ;  when  the  animal  is  made  to  fly  its  movements 
are  directed  by  the  sense  of  sight,  the  optic  lobes  being  still  intact, 
and  it  will  select  a  perch  to  settle  on  in  preference  to  the  floor. 
It  will  start  at  a  noise ;  it  will  not  eat  voluntarily ;  it  exhibits  no 
emotions  such  as  fear,  sexual  feeling,  or  maternal  instincts. 

In  mammals  the  operation  of  extirpation  of  the  brain  is  attended 
with  such  severe  haemorrhage  that  the  animal  dies  very  rapidly,  but 
in  some  few  cases  where  the  animals  have  been  kept  alive,  the 


724  FUNCTIONS  OF  THE  CEREBRUM  [CH.  L. 

phenomena  they  exhibit  are  similar  to  those  shown  by  a  frog  or 
pigeon.  The  difficulty  of  the  operation  was  overcome  by  Goltz  of 
Strassburg,  in  dogs,  by  removing  the  cerebrum  piecemeal.  One  dog 
treated  in  this  way  lived  in  good  health  for  eighteen  months,  when  it 
was  killed  in  order  that  a  thorough  examination  of  the  brain  might 
be  made.  It  was  then  found  that  not  only  the  hemispheres  but  the 
main  parts  of  the  optic  thalamus  and  corpus  striatum  had  been 
removed  also.  Though  it  could  still  carry  out  coordinated  move- 
ments, its  reactions  were  entirely  reflex,  and  memory,  emotions, 
feelings,  or  the  capacity  to  learn  were  absent. 

The  higher  animal  loses  just  those  characters  which  distinguish 
it  from  the  lower  ones.  It  is  difficult  to  prophesy  what  would 
happen  if  as  extensive  operations  were  carried  out  in  a  monkey  or  a 
man.  But  so  far  as  extirpation  has  been  observed,  the  initial  paralysis 
(which  is  seen  also  in  the  dog)  does  not  disappear  so  rapidly  or  so 
completely.  In  man,  the  tendency  to  recover  is  least. 

If  we  now  compare  these  effects,  it  is  seen  that  the  results  of  the 
operation  becomes  progressively  greater  as  we  ascend  the  scale.  The 
higher  the  animal,  the  more  fatal  the  effects,  the  immediate  disturb- 
ance more  severe,  the  return  of  function  slower,  and  the  permanent 
loss  greater.  The  long  life  of  G-oltz's  dog  was  doubtless  due  to  the 
fact  that  the  removal  was  accomplished  by  several  operations. 

This  is  anatomically  explicable  when  we  remember  that  the 
anterior  horn  cells  are  influenced  chiefly  by  two  sets  of  impulses, 
those  which  enter  the  cord  by  the  posterior  roots,  and  those  which 
come  down  from  the  cerebrum  by  the  pyramidal  tracts.  In  the  lower 
animals  the  pyramidal  pathway  is  insignificant,  and  when  it  is  inter- 
rupted the  disturbance  is  consequently  slight.  In  animals  below 
the  mammals  it  is  absent,  and  going  up  the  mammalian  scale  it 
becomes  more  and  more  important,  as  the  following  figures  show : — 

In  the  mouse  the  pyramidal  fibres  constitute  1'14  per  cent,  of  those  in  the  cord. 
„      guinea-pig     „  „  3'0  „  „ 

„      rabbit  „  „  „ 

»      cat  ,,  „  7'76  ,,  ,, 

„      man  „  „  11-87 

We  can  therefore  quite  readily  understand  that  in  the  apes  and 
in  man,  a  damage  to  the  cortex  which  causes  degeneration  of  these 
tracts  will  cut  off  many  impulses  to  the  anterior  cornual  cells,  and 
produce  a  greater  or  less  degree  of  paralysis. 

There  are  80,000  fibres  in  each  pyramidal  tract  of  the  human  cord.  They  are, 
moreover,  not  the  only  tracts  which  connect  the  cerebrum  to  the  spinal  cord,  and 
section  of  these  other  tracts  (see  p.  656)  may  produce  quite  as  marked  paralysis. 
In  man,  it  appears  that  when  the  pyramidal  tracts  are  diseased,  it  is  the  finer  and 
more  delicate  movements  which  are  permanently  lost  (Schafer.). 


CH.  L.]  CEREBRAL  LOCALISATION  725 

Localisation  of  Cerebral  Functions. 

The  different  parts  of  the  brain  and  of  its  cortex  are  related  to 
different  parts  of  the  body.  The  right  hemisphere,  for  instance,  con- 
trols the  voluntary  movements  on  the  left  side  of  the  body,  and 
receives  sensory  impulses  from  the  left  side,  and  vice  versd. 

Then  in  each  hemisphere  there  are  certain  areas,  termed  motor 
areas,  which  are  the  starting-points  of  those  volitional  impulses  which 
give  rise  to  movements;  and  other  areas  primarily  concerned  in  the 
reception  of  sensory  impulses ;  these  are  termed  sensory  areas.  These 
various  areas  have  been  mapped  out  by  means  of  experiments  on 
animals,  and  by  the  observation  of  disease  in  man. 

Before  these  facts  were  ascertained  it  was  usual  for  physiologists 
to  say  that  "  the  brain  acts  as  a  whole,"  and  although  we  do  not  now 
attach  the  same  meaning  to  that  phrase  as  did  the  physiologists  of 
the  past,  it  still  has  an  underlying  substratum  of  truth.  Let  us  take 
an  example,  and  imagine  the  smell  of  an  orange ;  such  an  abstract 
idea  of  an  isolated  sensation  is  impossible ;  we  cannot  think  of  the 
smell  of  the  orange  apart  from  the  other  characteristics  of  the  fruit, 
the  smell  recalls  the  taste,  the  shape,  the  colour,  the  act  of  peeling  it, 
fingering  it,  cutting  it,  eating  it,  and  so  forth.  One  sensation  due  to 
the  activity  of  one  area,  such  as  the  olfactory  area,  calls  into  play  the 
activity  of  other  sensory  areas,  and  of  the  motor  areas,  and  of  the 
links  between  the  sensory  and  motor  areas.  The  brain  is  acting  as 
a  whole  because  its  various  parts  are  called  into  play  simultaneously, 
though  the  whole  brain  is  not  concerned  in  each  of  the  component 
sensations  and  volitions  associated  with  any  particular  mental  state. 

Moreover,  the  doctrine  of  cerebral  localisation  is  not  accurately 
expressed  by  the  statement  that  a  cortical  centre  is  one,  the  stimula- 
tion of  which  produces  a  definite  response,  and  the  extirpation  of 
which  abolishes  the  response.  We  shall,  for  instance,  immediately 
see  that  the  stimulation  of  certain  areas  in  the  dog's  brain  produces 
certain  movements,  but  Goltz  showed  that  in  his  dogs,  the  removal 
of  an  entire  hemisphere  did  not  cause  permanent  paralysis  of  the 
opposite  side  of  the  body. 

In  the  central  nervous  system  there  are  few  or  no  places 
where  only  one  set  of  nerve  units  are  situated,  with  fibres  passing 
to  or  from  them.  Every  locality  has  several  connections  with 
other  parts,  and  also  fibres  passing  through  it  which  connect  together 
the  parts  on  all  sides  of  it.  Hence  in  extirpating  even  a  limited 
area,  numerous  pathways  are  interrupted,  and  the  damage  is  con- 
sequently widespread.  Much  of  the  disturbance  produced  at  first 
gradually  passes  away,  and  the  temporary  effects  must  be  distinguished 
from  those  which  are  permanent ;  the  permanent  effects  have  the 
greater  significance  of  the  two.  Moreover,  it  is  clear  that  the  relative 


726  FUNCTIONS  OF  THE  CEREBRUM  [CH.  L. 

and  absolute  value  of  any  locality  in  the  central  nervous  system 
depends  largely  on  the  degree  to  which  centralisation  has  progressed, 
and  on  the  amount  of  connection  between  the  various  areas.  The 
closer  the  connection,  the  more  numerous  and  intricate  the  path- 
ways, the  greater  will  be  the  permanent  effects  of  an  extirpation, 
and  the  recovery  of  function  the  more  remote.  The  lower  the 
animal  in  the  zoological  series,  or  the  less  the  age  of  the  animal,  the 
more  imperfectly  developed  will  be  the  connecting  strands,  and  so 
the  possibility  of  other  parts  taking  up  to  some  extent  the  functions 
of  those  that  are  removed  will  be  increased. 

The  earliest  to  work  in  the  direction  of  localisation  were  Hitzig 
and  Fritsch.  The  subject  was  then  taken  up  by  Terrier  and  Yeo, 
and  later  by  Schafer,  Horsley,  etc.,  in  this  country,  and  by  Munk 
and  many  others  in  Germany. 

The  main  point  which  these  researches  have  brought  out  is 
what  we  have  just  termed  the  overwhelming  importance  of  the 
cortex;  it  contains  the  highest  cerebral  centres.  Before  Hitzig 
began  his  work,  the  corpus  striatum  was  regarded  as  the  great  motor 
centre,  and  the  optic  thalamus  as  the  chief  centre  of  sensation ;  and 
the  idea  that  the  basal  ganglia  were  so  important  arose  from  the 
examination  of  the  brains  of  people  who  had  died  from,  or  at  least 
suffered  from,  cerebral  haemorrhage. 

The  most  common  situation  for  cerebral  haemorrhage  is  either  in 
the  region  of  the  corpus  striatum  or  optic  thalamus ;  it  was  noticed 
that  motor  paralysis  was  the  most  marked  symptom  if  the  corpus 
striatum  was  injured,  and  sensory  paralysis  if  the  optic  thalamus 
was  injured.  The  paralysis,  however,  is  due,  not  to  injury  of  the 
basal  ganglia,  but  of  the  neighbouring  internal  capsule.  The  internal 
capsule  consists  in  front  of  the  motor  fibres  passing  down  from  the 
cortex  to  the  cord,  and  behind  of  the  sensory  fibres  passing  up  from 
the  cord  to  the  cortex  (see  p.  689).  Hence,  if  these  fibres  are  ploughed 
up  by  the  escaping  blood,  paralysis  naturally  is  the  result.  If  a 
haemorrhage  or  injury  is  so  limited  as  to  affect  the  basal  ganglia  only, 
and  not  the  fibres  that  pass  between  them,  the  resulting  paralysis  is 
slight  or  absent. 

The  question  will  next  be  asked :  What,  then,  is  the  function  of 
the  basal  ganglia  ?  They  are  what  we  may  term  subsidiary  centres : 
the  corpus  striatum,  principally  in  connection  with  movement,  and 
the  optic  thalamus,  in  connection  with  sensation,  including  the  sense 
of  vision,  as  its  name  indicates. 

A  subsidiary  centre  may  be  compared  to  a  subordinate  official  in 
an  army.  The  principal  centre  may  be  compared  to  the  commander- 
in-chief.  This  highest  officer  gives  a  general  order  for  the  movement 
of  a  body  of  troops  in  a  certain  direction ;  we  may  compare  this  to 
the  principal  motor-centre  of  the  cortex  sending  out  an  impulse  for 


CH.  L.]  MOTOR  AND  SENSORY  AREAS  727 

a  certain  movement  in  a  limb.  But  the  general  does  not  give  the 
order  himself  to  each  individual  soldier,  any  more  than  the  cerebral 
cortex  does  to  each  individual  muscle ;  but  the  order  is  first  given 
to  subordinate  officers,  who  arrange  exactly  how  the  movement  shall 
be  executed,  and  their  orders  are  in  the  end  distributed  to  the 
individual  men,  who  must  move  in  harmony  with  their  fellows  with 
regard  to  both  time  and  space.  So  the  subsidiary  nerve-centres  or 
positions  of  relay  enable  the  impulse  to  be  widely  distributed  by 
collaterals  to  numerous  muscles  which  contract  in  a  similar  orderly, 
harmonious,  and  coordinate  manner. 

There  is  just  the  same  sort  of  thing  in  the  reverse  direction  in 
the  matter  of  sensory  impulses.  Just  as  a  private  in  the  army, 
when  he  wishes  to  communicate  with  the  general,  does  so  through 
one  or  several  subordinate  officers,  so  the  sensory  impulse  passes 
through  many  cell-stations  or  subsidiary  centres  on  the  way  to  the 
highest  centre,  where  the  mental  process  called  sensation,  that  is, 
the  appreciation  of  the  impulse,  takes  place. 

There  are  two  great  experimental  methods  used  for  determining 
the  function  of  any  part  of  the  cerebrum.  The  first  is  stimulation ; 
the  second  is  extirpation.  These  words  almost  explain  themselves ; 
in  stimulation  a  weak  interrupted  induction  current  is  applied  by 
means  of  electrodes  to  the  convolution  under  investigation,  and  the 
resulting  movement  of  the  muscles  of  the  body,  if  any  occurs,  is 
noticed.  In  extirpation  the  piece  of  brain  is  removed,  and  the  result- 
ing paralysis,  if  any,  is  observed. 

It  is  essential,  when  the  experiment  of  stimulating  the  cortex  of  the  brain  is 
being  performed,  that  the  animal  should  be  anaesthetised  and  absolutely  uncon- 
scious, otherwise  voluntary  or  reflex  actions  will  occur  which  mask  those  produced 
by  stimulation.  If,  however,  the  animal  is  too  deeply  under  the  influence  of  a 
narcotic  the  brain  is  inexcitable.  In  an  anaesthetised  animal  the  brain  is  inactive, 
and  if  methylene  blue  is  injected  into  the  blood,  the  brain  is  seen  to  be  of  a  blue 
colour.  If,  however,  a  spot  of  the  cerebral  surface  is  stimulated,  that  part  of  the 
brain  is  thrown  into  action,  oxygen  is  used  up,  and  the  methylene  blue  is  reduced, 
and  in  consequence  that  area  of  the  brain  loses  its  blue  tint.  If  the  animal  is  so 
deeply  narcotised  that  the  brain  does  not  discharge  an  impulse,  the  part  stimulated 
remains  blue. 

By  such  means  the  cortex  has  been  mapped  out  into  what  we 
may  term  motor  areas  and  sensory  areas. 

Motor  area. — The  name  Rolandic  area  which  this  part  of  the 
brain  has  also  received  is  derived  from  its  anatomical  position. 

Stimulation  of  the  motor  area  produces  movement  of  some  part 
of  the  opposite  side  of  the  body ;  excitation  of  the  same  spot  is  always 
followed  by  the  same  movement  in  the  same  animal.  In  different 
animals  excitation  of  anatomically  corresponding  spots  produces 
similar  or  corresponding  results.  It  is  this  which  has  enabled 
one  to  apply  the  results  of  stimulating  areas  of  the  monkey's 


728 


FUNCTIONS  OF  THE  CEREBRUM 


[CH.  L. 


brain  to  the  elucidation  of  the  function  of  the  similar  brain  of 
man. 

If  the  stimulation  used  is  too  powerful  the  movement  spreads  to 
other  parts,  and  a  considerable  portion  of  the  body  may  be  thrown 
into  convulsive  movements  similar  to  those  seen  in  epilepsy. 

Extirpation,  or  removal,  of  these  areas  produces  paralysis  of  the 
same  groups  of  muscles  which  are  thrown  into  action  by  stimulation. 

The  degeneration  tracts  after  destruction  of  the  motor  area  are 
shown  in  fig.  447.  The  shaded  area  in  each  case  represents  the 
injured  or  degenerated  material ;  A  in  the  cortex,  B  in  the  anterior 
part  of  the  posterior  limb  of  the  internal  capsule,  c  in  the  middle 


CORD 


MID.   BRAIN 


FIG.  447. — Degeneration  after  destruction  of  the  Rolandic  area  of  the  right  hemisphere. 
(After  Gowers.) 

of  the  crusta  of  the  mid  -  brain,  D  in  the  pyramidal  bundles 
of  the  pons,  E  in  the  pyramid  of  the  bulb,  and  F  in  the  crossed 
and  direct  pyramidal  tracts  of  the  cord. 

Sensory  areas. — Stimulation  of  these  produces  no  direct  move- 
ments, but  doubtless  sets  up  a  sensation  called  a  subjective  sensation ; 
that  is,  one  produced  in  the  animal's  own  brain,  and  this  indirectly 
leads  to  movements  which  are  reflex;  thus  on  stimulating  the 
auditory  area  there  is  a  pricking  up  of  the  ears ;  on  stimulating  the 
visual  area  there  is  a  turning  of  the  head  and  eyes  in  the  direction 
of  the  supposed  visual  impulse.  That  such  movements  are  reflex 
and  not  direct,  is  shown  by  the  long  period  of  delay  intervening 
between  the  stimulation  and  the  movement. 

Extirpation  of  a  sensory  area  leads  to  loss  of  the  sense  in  question. 


CH.  L.]  HEMIPLEGIA   AND   MONOPLEGIA  729 

The  rougher  experiments  performed  by  nature  in  the  shape  of 
diseases  of  the  brain  produce  corresponding  results. 

Some  diseases  are  of  the  nature  of  extirpation. 

An  instance  of  this  is  cerebral  haemorrhage.  If  the  haemorrhage 
is  in  the  region  of  the  internal  capsule,  it  cuts  through  fibres  to  the 
muscles  of  the  whole  of  the  opposite  side  of  the  body,  as  they  are 
all  collected  together  in  a  narrow  compass,  and  the  condition 
obtained  is  called  Tiemiplegia.  The  varieties  of  hemiplegia  are 


FIG.  448.— Brain  of  dog,  viewed  from  above.  F,  frontal  fissure,  sometimes  termed  crucial  sulcus, 
corresponding  to  the  fissure  of  Rolando  in  man.  6',  fissure  of  Sylvius,  around  which  the  four 
longitudinal  convolutions  are  concentrically  arranged;  1,  flexion  of  head  on  the  neck,  in  the 
median  line ;  2,  flexion  of  head  on  the  neck,  with  rotation  towards  the  side  of  the  stimulus ;  3, 
4,  flexion  and  extension  of  anterior  limb;  5,  6,  flexion  and  extension  of  posterior  limb;  7,  8,  9, 
contraction  of  orbicularis  oculi,  and  the  facial  muscles  in  general.  The  unshaded  part  is  that 
exposed  by  opening  the  skull.  (Dalton.) 

numerous,  according  as  motor  or  sensory  fibres  are  most  affected, 
and  in  one  variety  of  hemiplegia,  called  crossed  hemiplegia,  the  face 
is  paralysed  on  one  side  of  the  body,  the  limbs  on  the  other ;  this 
is  due  to  injury  of  the  tracts  in  the  bulb,  above  the  crossing  of  the 
pyramids. 

If  now  the  haemorrhage  occurs  on  the  surface  of  the  brain,  a  much 
more  limited  paralysis,  called  monoplegia,  is  the  result ;  if  the  arm  area 
is  affected,  there  will  be  paralysis  of  the  opposite  arm ;  if  the  leg 
area,  of  the  opposite  leg ;  if  a  sensory  area,  there  will  be  loss  of  the 
corresponding  sense. 


730 


FUNCTIONS  OF  THE  CEREBRUM 


[CH.  L. 


Some  diseases,  on  the  other  hand,  act  as  the  induction  currents 
do  in  artificial  stimulation ;  they  irritate  the  surface  of  the  brain ; 
such  a  disease  is  a  tumour  growing  in  the  membranes  of  the  brain ; 
if  the  tumour  irritates  a  piece  of  the  motor  area,  there  will  be 
involuntary  movements  in  the  corresponding  region  of  the  body; 
these  movements  may  culminate  in  the  production  of  epileptiform 
convulsions  commencing  in  the  arm,  leg,  or  other  part  of  the  body 
which  corresponds  to  the  brain  area  irritated.  It  is  these  cases  of 
"  Jacksonian  Epilepsy  "  which  have  given  the  best  results  in  surgery ; 
the  movement  produced  is  an  indication  of  the  area  of  the  brain 
which  is  being  irritated,  and  the  surgeon  after  trephining  is  able  to 
remove  the  source  of  the  mischief.  If  the  area  of  the  brain  which 
is  irritated  is  a  sensory  area,  the  result  produced  is  a  subjective 
sensation,  similar  to  what  we  imagine  is  produced  in  animals  with 
an  electric  current. 

We  may  now  proceed  from  these  general  considerations  to 
particular  points,  and  give  maps  of  the  brain  to  show  the  areas  we 
have  been  speaking  of. 

Fig.  448  is  a  view  of  the  dog's  brain.  It  is  convenient  to  take 
this  first  because  it  was  the  starting-point  of  the  experimental  work 
on  the  subject  in  the  hands  of  Hitzig  and  Fritsch.  If  the  text 
beneath  the  figure  is  consulted,  it  will  be  seen  that  the  motor  areas, 
mapped  out  by  the  method  of  stimulation,  are  situated  in  the 
neighbourhood  of  the  crucial  sulcus,  which  probably  corresponds  to 
the  fissure  of  Eolando  in  man. 

Coming  next  to  the  brain  of  the  monkey,  figure  449  is  repro- 
duced from  Ferrier's  book.  He  marked  out  the  surface  into  a 

number  of  circles,  stimu- 
lation of  each  of  which 
produced  movements  of 
various  sets  of  muscles, 
face,  arm,  and  leg,  from 
below  upwards ;  extirpa- 
tion of  these  same  areas 
produced  the  correspond- 
ing paralysis.  It  will  be 
further  noticed  that  these 
areas  are  all  grouped 
around  the  fissure  of 
Eolando,  particularly  in 
the  ascending  frontal  con- 
volution. 

Much  of  our  knowledge  concerning  the  localisation  of  the  motor 
area  in  the  human  brain  has  been  deduced  from  experiments  on  the 
lower  monkeys.  Valuable  as  such  knowledge  is,  infinitely  more 


FIG.  449. 


CH.  L.]  THE  CHIMPANZEE'S  BRAIN  731 

useful  knowledge,  from  the  standpoint  of  the  human  brain,  would 
be  obtained  by  examining  the  brains  of  those  monkeys  nearest  to 
man,  which  are  known  as  the  anthropoid  apes.  The  difficulty  and 
expense  of  obtaining  such  animals  has  largely  deterred  investigators 
from  performing  such  experiments.  Horsley  and  Beevor  examined 

Anus  b.vagina. 
Toes  ,.<'' SidciLs 

Ank(e  \         ,*/•"     /centralis  Abdomen 

knee        '^^.^^J^.^^r^    ^.Chest 


Fingers 
b  thumb... 


fy*1'*   /Closure 

Hose      of  iaw^     ,  .    .          ,  ^^   .     ^^ 

°*&*    Vocal  SulcU*  Centr&Us 

cord&     Mastication 

Fm.  450.— Brain  of  Chimpanzee.  Left  hemisphere  viewed  from  side  and  above  so  as  to  obtain  the 
configuration  of  the  Rolandic  area.  The  figure  involves  some  foreshortening  about  both  ends  of 
the  sulcus  centralis  or  fissure  of  Rolando.  The  extent  of  the  so-called  motor  area  on  the  free 
surface  of  the  hemisphere  is  indicated  by  black  stippling  which  extends  back  to  the  central  sulcus. 
Much  of  the  "  motor  "  area  is  hidden  in  sulci ;  for  instance,  it  extends  into  both  the  central  and 
precentral  sulci.  The  names  printed  in  capitals  on  the  stippled  area  indicate  the  main  subdivisions 
of  the  "motor"  area;  the  names  printed  small  outside  the  brain  indicate  by  their  pointing  lines 
some  of  the  chief  subdivisions  of  the  main  areas.  But  there  is  much  overlapping  of  the  areas  which 
it  is  not  possible  to  indicate  in  a  diagram  of  this  kind.  The  shaded  regions  marked  "  eyes  "  in  the 
frontal  and  occipital  regions  indicate  the  areas  which  under  faradisation  yield  conjugate  movements 
of  the  eyeballs.  S.F.  =  superior  frontal  sulcus.  S.Pr.  =  superior  precentral  sulcus.  I. Pr.  =  inferior 
precentral  sulcus.g( After  Sherrington  and  Griinbaum.) 

the  brain  of  an  orang-outang  some  years  ago,  and  now  Sherrington 
and  Griinbaum  have  made  a  number  of  experiments ;  several  speci- 
mens of  two  species  of  chimpanzee,  the  orang  and  the  gorilla,  have 
been  examined.  Their  conclusions  are  of  great  importance.  The 
above  figure  (fig.  450)  of  the  chimpanzee's  brain  shows  what  has 
been  found;  the  orang  and  the  gorilla  gave  practically  the  same 


732  FUNCTIONS  OF  THE  CEKEBRUM  [CH.  L. 

results,  and  no  doubt  the  human  brain  would  give  identical  results 
also  if  it  could  be  examined. 

The  method  used  is  to  expose  the  brain  in  an  anaesthetised  animal, 
and  thoroughly  explore  it  with  a  weak  faradic  current,  one  electrode 
being  placed  on  the  brain,  and  the  other  attached  to  an  indifferent 
part  of  the  animal's  body.  This  allows  of  finer  localisation  than  is 
possible  with  the  ordinary  double-point  electrodes. 

The  motor  area  includes  continuously  the  whole  length  of 
the  ascending  frontal,  or  as  it  is  sometimes  called,  the  precentral 
convolution.  It  never  extends  behind  the  central  sulcus,  or, 
as  it  is  sometimes  called,  the  fissure  of  Eolando.  On  the  mesial 
surface  it  extends  but  a  short  distance,  and  never  as  far  as  the 
calloso-marginal  fissure.  The  motor  area  extends  also  into  the  depth 
of  the  Eolandic  and  other  fissures;  the  part  of  the  excitable  area 
thus  hidden  equals  or  may  even  exceed  that  on  the  free  surface  of 
the  hemisphere.  The  arrangement  of  the  various  regions  of  the 
musculature  follow  the  segmental  sequence  of  the  cranio-spinal  series 
to  a  remarkable  extent ;  in  fact,  the  excitable  area  may  be  compared 
to  the  spinal  cord  upside  down.  The  accompanying  figure  indicates 
this  better  than  any  verbal  description. 

It  cannot  fail  to  strike  even  a  superficial  observer  how  large 
the  cortical  area  is  that  deals  with  movements  of  the  head  and  arm 
regions  when  compared  with  that  of  the  lower  limb,  and  still  more 
with  that  of  the  trunk.  The  trunk  itself  has  a  larger  mass  of 
muscular  tissue,  but  it  is  in  the  head  region  (which  includes  the 
complex  movements  of  the  tongue  and  such  structures  as  the  vocal 
cords)  and  in  the  arm  and  hand  that  the  movements  are  most  varied 
and  most  delicate.  No  doubt  this  is  the  explanation  of  the  greater 
size  of  their  cortical  representation. 

It  is  these  finer  movements  which  are  most  affected  by  a  cortical 
injury,  and  which  exhibit  least  recovery;  in  the  upper  limb,  for 
instance,  the  shoulder  muscles  will  be  the  least,  and  the  hand  the 
most  paralysed. 

In  experiments  on  unilateral  extirpation  in  animals,  and  in 
destructive  lesions  of  one  side  of  the  brain  in  man,  it  is  the  muscles 
which  act  normally  unilaterally  which  are  most  paralysed.  The 
muscles  which  normally  move  bilaterally,  e.g.,  the  chest  muscles  in 
breathing,  the  trunk  muscles  in  maintaining  an  erect  position,  are 
comparatively  little  affected ;  the  spinal  centres  of  such  muscles  are  no 
doubt  connected  by  commissural  fibres,  and  therefore  can  be  affected 
from  both  sides  of  the  brain. 

The  marginal  convolution  on  the  mesial  surface  of  the  hemisphere  was  first 
investigated  by  Schafer  and  Horsley,  in  the  lower  monkeys.  They  found  in  these 
animals  that  it  contained  a  considerable  extension  of  the  "  motor  "  area,  including 
the  cortical  centres  for  the  trunk  muscles.  This,  at  any  rate,  is  not  the  case  for  the 
higher  apes,  and  therefore  probably  is  not  true  for  man. 


CH.  L  ] 


THE  SPEECH   AND  TACTILE  AREAS 


733 


It  will  be  noticed  in  the  diagram  (fig.  450)  that  there  are  two 
regions  of  the  brain  from  which  eye  movements  can  be  elicited  ;  one 
is  in  the  frontal  lobe,  the  other  at  the  occipital  pole.  The  frontal  eye 
area  is  the  motor  centre  for  conjugate  movements  of  the  two  eyeballs, 
and  in  the  lower  monkeys  is  continuous  with  the  rest  of  the  motor 
area,  but  in  the  higher  monkeys  and  man  is  separated  from  the 
Eolandic  area  by  a  field  of  inexcitable  cortex.  The  occipital  region 
from  which  eye  movements  can  be  obtained  is  the  visuo-sensory 
sphere  (see  p.  736). 

The  next  illustration  is  an  outline  map  of  the  left  cerebral  hemi- 
sphere in  man.  In  it  are  indicated  the  various  motor  and  sensory 
areas,  which  are  largely  deduced  from  experiments  on  the  higher 
monkeys. 


VISUO- PSYCHIC  SPHERE 


VISUO-SENSORY   SPHERE 


FIG.  451. — Left  cerebral  hemisphere,  outer  surface.    The  lobes  and  the  principal  sulci  are  indicated  by 
their  initial  letters  ;  A.E.M.,  anterior  centre  for  eye  movements  ;  B.C.,  Broca's  convolution. 

One  part  of  the  motor  area  is  peculiar  to  man,  and  that  is : — 
The  Speech  Centre. — This  is  surrounded  in  the  diagram  by  a 
dotted  circle  and  marked  B.C.  There  are  other  centres  concerned  in 
speech,  as  we  shall  see  when  considering  the  question  of  association 
fibres ;  but  this  is  the  centre  for  the  muscular  actions  concerned  in 
speech.  The  discovery  of  this  centre  was  the  earliest  feat  in  the  direc- 
tion of  cerebral  localisation.  It  was  discovered  by  a  French  physician 
named  Broca ;  he  noticed  that  patients  who  died  after  hsemorrhage 
in  the  brain,  but  who  previous  to  death  exhibited  a  curious  disorder 
of  speech  called  aphasia,  were  found,  after  death,  to  have  the  seat  of 
the  hsemorrhage  in  this  convolution.  The  convolution  is  generally 
called  Broca's  convolution.  Experiments  on  animals  are  useless  in 
discovering  the  centre  for  speech.  Sherrington  found  in  the  higher 
apes  that  faradisation  of  the  Broca  area  does  not  evoke  vocalisation. 

The  most  curious  fact  about  the  speech-centre  is  that  it  is  uni- 
lateral ;  it  is  situated  only  on  the  left  side  of  the  brain,  except  in 
left-handed  people,  where  it  is  on  the  right.  We  are  thus  left- 
brained  so  far  as  the  finer  movements  of  the  hand-muscles  are  con- 


734:  FUNCTIONS  OF  THE  CEREBRUM  [CH.  L. 

earned,  as  in  writing,  and  we  are  also  left-brained  in  regard  to  speech, 
an  action  intimately  associated  with  writing.  There  is  but  little 
doubt  that  spoken  language  originated  from  gesture  language;  in 
fact,  one  sees  this  in  children  learning  to  speak.  In  gestures  the 
right  hand  (and  left  brain)  will  take  a  prominent  part;  hence  the 
unilateral  position  of  the  speech  centre  receives  a  rational  develop- 
mental explanation. 

That  Broca's  area  is  the  chief  speech  centre  has  for  long  been  a  matter  of  doubt 
among  physiologists  and  pathologists.  The  recent  researches  of  Marie  have  thrown 
further  doubt  upon  the  hypothesis ;  for  he  has  shown  that  in  many  cases  of 
aphasia  Broca's  area  is  uninjured,  and  that  in  cases  where  Broca's  area  is  injured, 
aphasia  is  not  always  present.  His  main  conclusion  is  that  injury  to  Broca's 
convolution  is  only  one  factor  in  the  causation  of  aphasia  ;  the  other  areas  related 
to  the  speech  mechanism  are  situated  more  posteriorly,  and  are  called  the  visual 
word  area  and  the  auditory  word  area  (see  further,  p.  741),  and  injury  to  these 
alone  will  produce  aphasia,  whereas  injury  to  Broca's  area  alone  will  not  do  so ;  he 
argues  that  the  cases  described  in  which  aphasia  followed  an  injury,  apparently 
limited  to  Broca's  area,  had  not  been  thoroughly  investigated,  and  if  the  other 
areas  had  been  properly  examined  injuries  would  have  been  found  there  also. 
These  conclusions  will  naturally  be  tested  in  the  future  by  others  who  have  the 
opportunity  of  examining  such  cases. 

The  Tactile  Area. — Volition  and  the  tactile  and  muscular  senses 
are  associated  together  so  closely  physiologically,  that  anatomically 
we  should  expect  to  find  the  commencement  of  the  volitional  fibres 
not  far  removed  from  the  terminations  of  the  sensory  fibres,  and  as  a 
matter  of  fact,  this  is  actually  the  case.  Some  of  the  sensory  fibres 
possibly  pass  direct  into  the  ascending  frontal  convolution,  but 
the  vast  majority  terminate  in  its  neighbour  the  ascending  parietal 
convolution,  which  is  on  the  other  side  of  the  central  or  Eolandic 
fissure.  In  the  early  days  of  brain  map-making,  the  ascending 
parietal  convolution  was  believed  to  be  a  part  of  the  motor  area,  and 
this  found  expression  in  such  diagrams  as  those  of  Terrier  (see  fig. 
449).  A  cortical  injury  in  man  seldom  involves  the  ascending 
frontal  without  also  involving  the  ascending  parietal,  and  so  loss  of 
sensation  and  motion  usually  go  together.  The  more  exact  methods 
introduced  by  Sherrington  and  Griinbaum  have,  however,  shown 
that  stimulation  of  the  ascending  parietal  produces  no  direct  move- 
ments ;  secondary  movements  may  be  elicited,  just  as  stimulation  of 
the  visuo-sensory  area  provokes  secondary  movements  of  the  eyes. 
Extirpation  of  the  ascending  parietal,  however,  leads  to  no  motor 
paralysis,  and  no  degeneration  of  the  pyramidal  tracts.  Histological 
examination  of  the  ascending  parietal  grey  matter  shows  it,  moreover, 
to  possess  the  structure  of  a  sensory  rather  than  of  a  motor  area. 
Before  this  distinction  was  recognised,  the  term  sensori-motor  was 
used  as  a  comprehensive  expression  to  include  the  functions  of  the 
two  convolutions  one  on  each  side  of  the  Eolandic  fissure.  The 
ascending  parietal  convolution  is  the  cortical  seat  of  those  sensations 


CH.  L.]  THE   VISUAL   AREA  735 

which  are  tactile  discriminatory,  and  related  to  position  and  move- 
ment of  the  muscles.  We  still  await  exact  information  regarding 
the  cortical  representation  of  sensations  of  pain  and  temperature. 

This  conclusion  regarding  the  sensory  function  of  the  ascending 
parietal  convolution  has  received  support  from  a  number  of  carefully 
observed  clinical  cases,  for  Sherrington  and  Grimbaum's  delimitation 
to  a  relatively  narrow  strip  of  what  had  previously  been  considered 
a  widespread  motor  territory,  left  for  some  time  uncertain  the 
function  of  the  remainder  of  the  original  motor  area — Munk's 
sensori-motor  field — lying  posterior  to  the  central  fissure.  The  most 
remarkable  confirmatory  evidence  regarding  the  sensory  functions  of 
what  we  may  call  the  post-central  convolution  has  been  recently 
afforded  by  two  patients,  who  voluntarily  allowed  Dr  Gushing  of 
Baltimore  the  opportunity  of  experimentally  testing  the  point  after 
operations  in  which  this  part  of  the  brain  was  exposed,  and  during  a 
time  they  were  in  a  conscious  state. 

In  both  of  them  characteristic  motor  responses  were  obtained 
from  the  precentral  gyrus  (ascending  frontal  convolution)  without 
any  conscious  sensation,  except  that  which  accompanies  forced  change 
of  position  in  the  parts  moved.  On  the  other  hand,  stimulation  of 
the  post-central  gyrus  (ascending  parietal  convolution)  produced  no 
movements,  but  gave  definite  sensory  impressions  which  were  likened 
by  one  patient  to  a  sensation  of  numbness,  and  by  the  other  to 
definite  tactual  impressions. 

There  is,  of  course,  a  close  connection  between  the  two  convolu- 
tions in  question,  by  short  association  fibres  passing  from  one  to  the 
other;  and  the  necessity  for  sensation  in  normally  provoking  the 
corresponding  motor  outflow  is  also  illustrated  by  the  following  experi- 
ment : — If  the  posterior  roots  of  the  spinal  nerves  are  divided  there  is 
a  loss  of  sensation,  and  so  the  sense  of  movement  cannot  reach  the 
brain  from  the  muscles,  and  consequently  the  muscles  are  not  called 
into  action ;  when  all  the  posterior  roots  coming  from  a  limb  in  a 
monkey  are  cut,  the  muscles,  so  far  as  voluntary  movements  are 
concerned,  are  as  effectually  paralysed  as  if  the  anterior  roots  of 
the  spinal  nerves  had  been  cut.  The  muscles,  however,  do  not 
degenerate  as  they  would  if  the  anterior  roots  had  been  cut.  They 
merely  undergo  a  small  amount  of  wasting,  due  to  want  of  use. 

The  Visual  Area. — The  lower  the  animal  in  the  series,  the 
more  readily  can  its  actions  be  controlled  by  sensory  impulses  which 
have  not  passed  through  the  cortex  cerebri.  A  decerebrated  bony 
fish  can  distinguish  colours,  a  frog  can  catch  flies,  even  a  pigeon  will 
select  its  perch,  though  it  takes  no  notice  of  food  or  of  people  who  try 
to  frighten  it.  A  dog  similarly  operated  on  is  practically  blind, 
though  it  will  blink  at  a  bright  flash  of  light.  In  the  lower  animals 
the  impulses  pass  in  to  the  primary  visual  centre  in  the  optic  lobes 


736  FUNCTIONS  OF  THE  CEREBRUM  [CH.  L. 

which  acts  as  the  centre  for  the  reflex;  the  higher  we  ascend  the 
animal  scale,  the  path  via  the  cortex  becomes  more  permeable,  of 
greater  value  or  even  indispensable,  and  the  reflexes  through  the 
lower  centres  of  less  importance;  not  only  so,  but  there  are  sub- 
divisions of  the  visual  cortical  area,  which  correspond  to  different 
regions  of  the  retinae. 

We  may  in  fact  speak  of  the  visuo-sensory  field  in  the  cortex  as 
the  cortical  retina  upon  which  the  impulses  from  the  actual  retina 
in  the  eye  are  projected,  in  a  manner  analogous  to  the  way  in  which 
the  field  of  vision  is  projected  upon  the  actual  retina. 

In  the  fishes  which  have  no  cortex  cerebri,  the  optic  lobes, 
analogous  to  the  C.  quadrigemina,  are  the  centres  for  vision.  In 
some  fishes,  a  small  number  of  the  fibres  of  the  optic  nerve  pass  into 
the  geniculate  body,  which  forms  a  cell-station  on  the  road  to  the 
posterior  region  of  the  cerebrum,  where  a  primitive  cortex  begins  to 
appear.  On  ascending  the  animal  scale,  this  group  of  fibres  becomes 
more  and  more  abundant,  and  this  part  of  the  cortex  becomes  more 
elaborate  in  structure.  When  we  reach  the  monkeys,  this  part  of 
the  brain  is  cut  off  from  the  rest  to  form  a  distinct  occipital  lobe  by 
the  parieto-occipital  fissure,  which  is  frequently  called  the  Affenspalte 
(ape's  split).  In  the  lower  monkeys  this  lobe  is  smooth  (fig.  427,  A, 
p.  691),  but  as  the  great  parietal  association  centres  get  larger  with 
increase  of  intelligence,  the  visuo-sensory  area  is  pushed  back,  and 
the  lobe  thrown  into  folds.  In  the  highest  apes,  and  in  the  lower 
races  of  mankind,  a  good  deal  of  the  visuo-sensory  sphere  is  still 
seen  on  the  external  cerebral  surface;  but  in  the  higher  races, 
most  is  pushed  round  on  to  the  mesial  surface.  This  calcarine  area 
is  also  named  the  striate  area,  because  it  is  characterised  by  the 
white  stripe  called  the  line  of  Gennari. 

Some  animals  have  panoramic  and  others  stereoscopic  vision. 
The  former  (mainly  vegetable  feeders)  have  eyes  set  laterally ;  each 
eye  receives  a  different  picture,  and  the  decussation  of  the  optic 
nerves  is  complete;  each  eye  sends  impulses  to  the  opposite  hemi- 
sphere. Animals  with  stereoscopic  vision  have  the  eyes,  as  in  man, 
in  front,  and  the  optic  axes  can  be  converged  so  that  an  object  is 
focussed  with  both  eyes.  This  becomes  necessary  in  carnivora,  which 
have  to  catch  moving  prey;  the  more  complex  the  movements  of  the 
fore-limbs,  the  greater  becomes  the  necessity  for  fixation  of  the  eyes 
to  guide  them.  In  such  animals  each  visual  area  corresponds  with 
the  same  half  of  both  retinae,  that  is,  with  the  opposite  half  of  the 
visual  field ;  the  lower  half  of  each  area  corresponds  with  the  upper 
half  of  each  half  field  of  vision,  and  vice  versd.  The  appearance  of 
the  macula  lutea  (with  cortical  representation  in  both  hemispheres) 
in  the  primates  is  the  culminating  point  in  visual  development  among 
the  mammals. 


CH.  L.]  THE  VISUAL  AREA  737 

A  man  or  an  animal  who  loses  both  eyes  is  blind,  but  in  time 
manages  to  find  his  way  about.  This  is  not  the  case  when  blindness 
is  produced  by  removal  or  disease  of  both  occipital  lobes ;  here,  the 
sense  of  orientation  is  lost  also,  for  the  association  of  sensory 
memories  and  motor  impulses  is  then  impossible. 

Kemoval  of  one  occipital  lobe  will  be  followed  by  different  results 
in  the  two  classes  of  animals  just  referred  to.  In  those  with  pano- 
ramic vision,  the  result  will  be  blindness  of  the  opposite  eye,  because 
the  decussation  of  the  optic  nerve  is  complete  at  the  chiasma. 
But  in  animals  such  as  monkeys  with  stereoscopic  vision  (in 
which  the  only  decussating  fibres  are  those  which  come  from  the 
inner  halves  of  the  two  retinae)  removal  of  one  occipital  lobe,  or 
disease  of  that  lobe  in  man,  produces  blindness  of  the  same  side  of 
each  retina,  or  inability  to  see  the  opposite  half  of  the  visual  field. 
This  is  called  hemianopsia ;  the  head  and  eyes  are  turned  to  one 
side,  namely,  the  side  of  injury  (conjugate  deviation  to  the  side  of  the 
injury).  Such  an  operation  does  not  destroy  vision  in  the  central 
portion  (macula  lutea)  of  either  retina,  because  each  macula  sends 
impulses  to  both  sides  of  the  brain.  Stimulation  of  one  visual  area 
leads  to  a  subjective  sensation  apparently  coming  from  the  same 
halves  of  both  retinae,  and  also  excites  the  solitary  cells  of  Meynert ; 
this  produces  conjugate  deviation  of  head  and  eyes  towards  the 
opposite  side  to  that  stimulated. 

These  solitary  cells  are  so  called  because  they  are  few  and  far 
between ;  they  are  large  cells  not  at  all  unlike  the  Betz  cells  of  the 
motor  cortex.  Their  axons,  no  doubt,  pass  in  long  association  tracts 
to  the  motor  eye  centre  of  the  frontal  region  and  to  the  corpora 
quadrigemina. 

The  optic  radiations  consist  of  (1)  sensory  fibres  from  the  optic 
tracts  via  the  external  geniculate  bodies;  (2)  efferent  fibres  to  the 
centres  for  eye-movements ;  and  (3)  association  fibres,  which  are  last 
developed.  The  last  named  link  one  convolution  to  others,  and  the 
two  hemispheres  together,  and  bring  about  association  of  ideas  of 
vision  in  both  hemispheres,  and  with  other  sensations.  A  large 
collection  of  such  fibres  runs  horizontally  through  the  grey  matter. 
This  white  stripe  is  often  visible  to  the  naked  eye ;  it  is  the  anatomical 
mark  of  the  visuo-sensory  cortex,  and  is  called  the  line  of  Gennari. 
The  visuo-psychic  region  (fig.  451)  has  no  line  of  G-ennari,  but 
possesses  many  small  and  medium-sized  pyramidal  cells  in  its  outer 
layers,  which  play  the  part  of  association  units,  where  memory 
pictures  are  stored  and  visual  sensations  correlated  with  those  from 
other  sense-organs;  the  higher  one  ascends  the  animal  scale,  the 
greater  becomes  the  depth  of  this  layer. 

The  eye  centre  in  the  frontal  lobe  is  separated,  in  the  higher 
apes  and  man,  by  inexcitable  grey  matter  from  the  rest  of  the 

3  A 


738  FUNCTIONS  or  THE  CEREBRUM  [CH.  L. 

motor  area.  No  cortical  centre  is  purely  motor  or  purely  sensory, 
and  this  one,  though  usually  called  motor,  has  its  sensory  complement 
probably  from  the  eyeballs  and  eyelids  (5th  nerve).  The  newly 
developed  grey  matter  between  it  and  the  Eolandic  region  is  an  area 
probably  concerned  in  the  association  of  eye  movements  with 
equilibration  and  the  maintenance  of  the  erect  position ;  we  know, 
moreover,  that  the  fibres  from  the  frontal  lobe  to  the  cerebellum  (the 
centre  for  equilibration)  are  very  numerous  (see  fig.  437,  A,  p.  699). 

The  Auditory  Area  is  in  the  posterior  part  of  the  upper 
temporal  convolution.  This  has  been  definitely  proved  by  clinical 
observation  in  man,  and  supported  by  experiments  on  animals,  though 
it  is  by  no  means  easy  to  ascertain  whether  or  not  an  animal  is  deaf. 
It  is  doubtless  surrounded,  as  are  the  visuo-sensory  area  and  other 
sense  areas,  by  a  psychic  or  association  sphere,  and  is  connected  to 
surrounding  parts,  and  especially  to  the  visual  area,  by  annectent  gyri. 
A  good  deal  of  the  auditory  area  is  situated  in  the  depth  of  the 
Sylvian  fissure  where  the  gyri  tranversales  which  cross  it  are  found. 

Taste  and  Smell  are  closely  connected ;  their  cerebral  area  is  the 
uncinate  and  hippocampal  gyrus,  and  the  tip  of  the  temporal  lobe. 
These  parts  are  relatively  more  important  in  animals  who  rely  upon 
smell  and  the  oral  sense  for  their  guidance.  This  part  of  the  cortex 
is  of  simpler  structure  than  the  rest,  and  on  account  of  its  early 
appearance  in  the  animal  scale  is  known  as  the  archipallium  (see 
p.  698). 

The  Silent  Areas.  —  On  referring  once  more  to  the  maps  of 
the  brain,  it  will  be  seen  that  there  are  many  blanks;  one  of 
these  is  in  the  anterior  part  of  the  frontal  region.  Extirpation 
or  stimulation  of  this  part  of  the  brain  in  animals  produces  but 
little  result.  The  large  size  of  this  portion  of  the  brain  is  very 
distinctive  of  the  human  brain,  and  it  has  therefore  been  sup- 
posed that  here  is  the  seat  of  the  higher  intellectual  faculties. 
Such  a  question  is  obviously  very  difficult  to  answer  by  experi- 
ments on  animals.  Both  experimental  physiology  and  pathology 
have  localised  the  sensory  areas  (and  sensations  are  the  materials 
for  intellect)  behind  the  Eolandic  fissure,  but  this  does  not 
necessarily  mean  that  the  frontal  convolutions  have  nothing  to 
do  with  intellectual  functions.  The  celebrated  American  crowbar 
accident  is  generally  quoted  as  a  proof  to  the  contrary;  owing 
to  the  premature  explosion  of  a  charge  of  dynamite  in  one  of  the 
American  mines  a  crowbar  was  sent  through  the  frontal  region  of 
the  foreman's  head,  removing  the  anterior  part  of  his  brain.  He  is 
usually  stated  to  have  subsequently  returned  to  his  work,  without 
any  noteworthy  symptoms.  Eecent  examination  of  the  records  of 
the  case  has  shown  that  this  is  not  correct ;  when  he  returned  to 
work  he  was  practically  useless,  having  lost  just  those  higher 


CH.  L.]  FUNCTION   AND   MYELINATION  739 

functions  which  are  so  important  in  the  superintendence  of  other 
people.  Mott's  observations  on  lunatics  show  that  this  region  is 
important  for  intellectual  operations,  though  not  so  important  as  the 
parietal  association  area  behind  the  Eolandic  area;  the  greater  the 
intellectual  development,  the  larger  and  more  convoluted  does  this 
parietal  region  become. 

The  association  fibres  have  been  the  subject  of  special  study  by 
Flechsig,  who  has  shown  that  in  the  development  of  the  brain  these 
are  the  last  to  become  myelinated ;  white  fibres  do  not  become  fully 
functional  until  they  receive  their  medullary  sheath.  This  coincides 
with  the  well-known  fact  that  association  of  ideas  is  the  last  phase  in 
the  psychical  development  of  the  child.  It  has  been  shown  that  the 
frontal  convolutions  are  connected  by  important  association  tracts 
with  the  more  posterior  regions  of  the  brain  (see  fig.  436,  p.  699), 
and  there  is  therefore  no  difficulty  in  understanding  that  the  frontal 
convolutions  play  the  part  of  a  centre  for  the  association  of  ideas,  or 
in  other  words  for  intellectual  operations. 

Function  and  Myelination. 

Flechsig's  embryological  method  has  given  us  most  valuable  knowledge  of  the 
structure  and  functions  of  the  human  brain.  The  method  depends  on  the  fact  that 
various  tracts  of  fibres  become  myelinated,  i.e.9  acquire  their  medullary  sheath  at 
successive  periods  of  time  in  development.  The  myelin  sheath  appears  three  or  four 
months  after  the  axis  cylinder  is  formed.  The  Weigert  method  of  staining  renders 


c.c 


M.O: 


Fin.  452.— Diagram  of  vertical  section  through  brain  of  new-born  child,  drawn  from  one  of  Flechsig's 
photographs.  The  section  was  treated  by  Weigert's  method,  by  which  myelinated  fibres  are  deeply 
stained.  Attention  is  drawn  to  the  deep  shading  indicating  myelination  around  the  central  fissure, 
which  corresponds  to  the  sensori-motor  area,  and  also  around  the  calcarine  fissure  in  the  visual 
sphere.  The  association  fibres  are  not  myelinated.  The  fibres  of  the  pyramidal  efferent  system 
have  also  no  myelin.  M.O.,  medulla  oblongata  ;  P.V.,  pons  Varolii ;  O.M.N.,  oculo-motor  nerve; 
O.C.,  optic  commissure;  F.A.C.,  frontal  association  centre;  C.C.,  corpus  callosum ;  C.  P.,  central 
fissure,  or  fissure  of  Rolando;  P.A.C.,  posterior  association  centre;  V.S.,  visual  sphere;  C.,  cere- 
bellum ;  S.C.,  spinal  cord. 

the  detection  of  a  medullary  sheath  an  easy  task.  Flechsig's  method  is  in  short  the 
complement  of  the  Wallerian  method.  In  the  former  method  the  tracts  are  isolated 
by  the  differences  in  the  origin  of  the  myelin  sheath ;  in  the  latter  method,  the  same 
object  is  obtained  by  observing  the  degeneration  which  is  most  noticeable  in  the 
same  sheath. 

In  the  central  nervous  system,  the  afferent  projection  fibres  are  myelinated  first ; 


740  FUNCTIONS  OF  THE  CEREBRUM  [CH.  L. 

the  efferent  projection  fibres  and  the  association  fibres  are  myelinated  later.  Thus 
in  the  human  foetus  the  peripheral  nerves  and  nerve-roots  become  myelinated  in  the 
fifth  month  of  intra-uterine  life ;  of  the  tracts  in  the  cord,  those  of  Burdach  and  Goll 
(exogenous  fibres  springing  from  the  cells  of  the  spinal  ganglia)  are  the  first  to  be 
myelinated ;  next  come  the  tracts  of  Flechsig  (dorsal  cerebellar)  and  of  Gowers 
(ventral  cerebellar) :  these  are  endogenous  fibres  springing  from  cells  within  the  cord. 
All  these  tracts  are  afferent.  The  pyramidal  tracts,  the  great  efferent  or  motor 
channels,  are  not  myelinated  until  after  birth.  The  whole  afferent  tract  is  myelinated 
at  birth ;  these  fibres  have  in  utero  been  exercised  in  conveying  impressions  to  the 
afferent  reception  centres,  the  stimuli  arising  from  contact  of  the  fretal  integuments 
with  the  maternal  tissues.  There  is  also  early  myelination  around  the  calcarine 
fissure  in  the  visual  sphere,  and  in  connection  with  the  areas  related  to  other  special 
senses.  This  is  shown  in  figs.  452  and  453,  where  the  condition  at  birth  and  that 
some  months  later  are  compared. 

Ambronn  and  Held  confirm  Flechsig  in  finding  that  the  afferent  fibres  are 
myelinated  before  the  efferent,  in  the  central  nervous  system,  but  in  the  case  of 
the  nerve-roots  this  is  reversed,  the  anterior  root-fibres  being  myelinated  before  the 
posterior. 

Held  has  also  demonstrated  the  important  influence  of  stimulus  on  myelination. 
His  experiments  were  made  on  cats,  dogs,  and  rabbits,  which  are  born  blind.  If 

C.F. 


FA.C.- 


Fia.  453.— Diagram  of  vertical  section  of  the  brain  of  a  child  5  months  of  age.  The  greater  part  of  the 
white  matter  now  shows  myelination,  thus  indicating  development  of  the  association  centres.  The 
letters  have  the  same  meaning  as  in  Fig.  452.  (After  Flechsig ;  Weigert  method  of  staining.) 

light  is  admitted  to  one  eye  by  opening  the  lid,  more  obvious  myelination  is  subse- 
quently found  in  the  corresponding  optic  nerve  than  in  that  of  the  opposite  side. 
This  is  not  due  to  the  irritation  caused  by  forcibly  opening  the  lid,  for  it  the  lid  be 
opened  and  the  animal  kept  in  the  dark,  no  difference  in  the  myelination  of  the  two 
optic  nerves  is  observable.  Flechsig  also  showed  that  a  child  born  at  8  months  had 
more  marked  myelination  of  its  optic  nerves,  a  month  later,  than  a  child  born  in  the 
usual  way  at  the  ninth  month. 

The  richness  of  the  brain  in  myelinated  fibres  increases  for  many  years  after 
birth  with  the  progress  of  intellectual  development.  Kaes  states  this  continues 
up  to  forty  years  of  age,  and  that  in  old  age  the  number  diminishes.  Myelin 
appears  to  be  necessary  for  the  functional  activity  of  nerve  tracts,  and  its 
development  progresses  part  passu  with  development  of  function ;  the  reverse 
change  (atrophy  and  degeneration)  correspondingly  accompanies  marked  disturb- 
ances of  function. 

Association  Fibres  and  Association  Centres. 

We  know  by  common  experience  that  any  group  of  muscles  can  be  voluntarily 
contracted  in  reply  to  any  form  of  stimulus,  cutaneous,  visual,  auditory,  etc.  If, 
for  instance,  the  wrist  is  flexed  in  response  to  an  auditory  stimulus,  the  nerve 


CH.  L.] 


MYELOGENETIC    FIELDS 


741 


impulses  pass  first  to  the  auditory  area,  then  by  certain  fibres  to  the  cerebral  cells 
which  control  the  muscles  of  the  arm.  The  fibres  which  connect  the  two  areas  are 
termed  association  fibres.  A  diagrammatic  view  of  the  principal  bundles  of 
association  fibres  is  given  in  fig.  436,  p.  699. 

The  term  "association  centres"  is  given  by  Flechsig  to  those  portions  of  the 
cortex  that  lie  between  the  sensory  centres.  The  function  of  these  centres 
is  first  to  furnish  pathways  between  the  several  centres,  and  secondly  to  retain 
as  memories  previous  sense  impressions,  so  that  in  action  they  may  modify  the 
impulses  sent  into  them,  and  by  these  modifications  adjust  to  an  almost  infinite 
degree  the  form  of  the  final  response. 

The  association  centres  comprise  a  very  large  area  of  the  cortex,  and  are 
divided  into  three: — (1)  The  great  anterior  association  centre  in  the  frontal 
lobe ;  (2)  the  posterior  association  centre  in  the  parieto-temporal  region ;  (3)  the 


FIG.  454. — Lateral  view  of  the  left  cerebral  hemisphere  of  man  (after  Donaldson).  V  is  the  cortical  area 
damage  to  which  produces  "  word  blindness  " ;  it  is  situated  in  the  angular  gyrus,  and  is  called  the 
visual  word  centre.  H  is  the  area  in  the  superior  temporal  convolution,  called  the  auditory  word 
centre,  damage  to  which  produces  "word  deafness."  S  is  Broca's  convolution,  damage  to  which 
produces  loss  of  audible  speech  (motor  aphasia);  this  is  the  motor  area  for  the  movements 
of  the  tongue,  vocal  cords,  etc.,  concerned  in  speaking;  Bastian  terms  it  the  glosso-kincesthetic  area. 
The  area  W,  called  by  Bastian  the  cheiro-kinwsthetic  area,  is  the  corresponding  region  concerned  in 
hand  movements,  damage  to  which  abolishes  the  power  of  writing  (agraphia). 

middle  association  centre ;  this  is  smaller  and  coincides  with  the  island  of  Reil. 
These  regions  are  in  fact  those  in  which  no  evident  response  follows  excitation  ; 
they  are  sometimes  called  the  "  latent  or  silent  or  inexcitable  cortex."  The  human 
brain  is  characterised  by  the  high  development  of  these  parts,  and  as  already 
explained  they  are  doubtless,  as  Flechsig  terms  them,  the  organs  of  thought. 

The  importance  of  the  association  of  ideas,  which  has  for  its  anatomical  basis 
the  association  of  cortical  centres,  will  be  at  once  grasped  when  one  considers  such 
complex  actions  as  speaking,  reading  aloud,  or  writing  from  dictation.  The 
accompanying  diagram  (fig.  454)  shows  the  position  of  the  main  centres  involved, 
particulars  of  which  will  be  found  in  the  small  text  beneath  the  figure. 

In  reading  aloud,  the  impressions  of  the  words  enter  by  the  eyes,  reach  that 
portion  of  the  visual  sphere  known  as  the  visual  word  centre,  travel  across  to  the 
auditory  word  centre  by  association  fibres,  where  the  memory  of  their  sounds  is 
revived';  another  tract  of  association  fibres  connects  this  to  the  sensori-motor  area 
in  Broca's  convolution  called  by  Bastian  the  alosso-kincesthetic  area,  whence  motor 
impulses  originate  which  finally  reach  the  muscles  concerned  in  pronouncing  the 
words  originally  seen. 

Writing  from  dictation  is  just  as  complex ;  the  course  of  the  impulses  is  by 
the  auditory  channels  to  the  auditory  word  centre,  then  by  association  tracts  to  the 
visual  word  centre,  where  the  shapes  of  the  letters  composing  the  words  are 
revived ;  another  association  tract  carries  the  impulse  thence  to  the  sensori-motor 


742 


FUNCTIONS  OF  THE  CEREBRUM 


[CH.  L. 


area  connected  with  the  movements  of  the  hand  (Bastian's  cheiro-kincesthetic  area} 
near  the  middle  region  of  the  Rolandic  cortex,  and  finally  the  movement  of  writing 
is  accomplished.  The  diverse  symptoms  exhibited  by  patients  suffering  from 
various  forms  of  aphasia  can  be  all  explained  by  more  or  less  extensive  damage 


FIG.  455.— Outer  surface  of  human  brain,  showing  Flechsig's  developmental  zones;  primary  (1—10) 
darkly  shaded ;  intermediate  (11—31),  less  deeply  shaded  ;  terminal  (32 — 36),  not  shaded.    (Flechsig.) 

either  to  the  centres  themselves  or  to  the  association  tracts  which  connect  them. 

In  the  cerebral  convolutions  the  fibres  become  myelinated  in  a  strictly 
regular  sequence;  some  convolutions  have  their  fibres  medullated  three  months 
before  birth,  while  in  others  complete  myelination  has  not  occurred  six  months  later. 


FIG.  456.— Inner  surface  of  same.    (Flechsig.) 

Fibres  of  equally  great  importance  become  medullated  at  the  same  time ;  those  of 
primary  importance  first,  and  so  on.  In  this  way,  myelogenetic  cortical  fields  can 
be  mapped  out,  which  retain  their  contours  for  some  time.  Thirty-six  of  such  fields 
were  made  out  by  Flechsig,  and  can  be  divided  chronologically  into  three  groups, 
primary,  intermediate,  and  terminal 

The  primary  fields  are  darkly  shaded  in  the  accompanying  diagrams  (figs.  455 
and  456). 


CII.  L.]        ELECTRICAL  VARIATION   IN   CENTRAL   NERVOUS   SYSTEM        743 

They  are  10  in  number,  and  are  those  provided  with  myelinated  fibres  at  birth  ; 
they  contain  the  seats  of  the  cortical  representation  of  all  the  senses.  To  No.  1  is 
assigned  the  cutaneous  and  muscular  sense ;  to  No.  2  the  sense  of  smell ;  to  No.  4 
that  of  vision ;  to  No.  5  that  of  hearing.  The  functions  of  some  of  the  primary 
areas  had  not  been  determined.  The  principal  efferent  projection  tracts  originate 
from  the  primary  fields  ;  thus  the  pyramidal  tract  starts  from  part  of  No.  1,  namely, 
from  the  ascending  frontal  convolution.  The  sensory  fibres  connected  with  the 
skin  and  muscles  terminate  in  the  ascending  parietal  convolution.  The  inferior 
fornix  is  connected  with  Nos.  2  and  3.  The  inner  bundle  of  the  pes  springs 
from  1  B,  6,  12,  14  and  15 ;  the  origin  of  the  outer  bundle  of  the  pes  is  doubtful. 
From  the  visual  area  (No.  4)  a  tract  arises  which  passes  mainly  into  the  anterior 
corpus  quadrigeminum ;  the  auditory  zone  (No.  5),  towards  which  a  tract  proceeds 
that  leads  from  the  internal  corpus  geniculatum,  sends  an  outgoing  tract  into  the 
column  of  Tiirck,  and  thus  motor  functions  of  the  upper  part  of  the  body  are 
possible  as  a  direct  result  of  auditory  impressions.  In  fact,  in  every  case  each 
primordial  sensory  zone  is  connected  with  a  well-defined  pair  of  tracts,  one  proceed- 
ing to  it  (cortico-petal)  and  the  other  from  it  (cortico-fugal).  It  is  thus  impossible  to 
speak  of  a  purely  motor  or  a  purely  sensory  area. 

The  terminal  areas  (Nos.  31  to  36,  unshaded  in  the  diagrams)  do  not  begin  to 
be  myelinated  until  at  least  a  month  after  birth.  These  and  the  majority  of  the 
intermediate  areas  (Nos.  11  to  31,  lightly  shaded  in  the  diagrams)  show  few  or  no 
projection  fibres  even  8  months  after  birth.  They  comprise,  in  fact,  the  association 
centres,  and  are  rich  in  long  association  fibres. 

Electrical  Variation  in  Central  Nervous  System. 

Du  Bois  Keymond  found  that  the  spinal  cord,  like  a  nerve, 
exhibits  a  demarcation  current  between  its  longitudinal  surface  and 
a  cross-section,  and  that  a  diminution  of  this  current  occurs  on 
excitation  (negative  variation).  Gotch  and  Horsley  investigated  the 
currents  of  the  cord  very  thoroughly.  If  the  Eolandic  area  of  the 
cortex  is  stimulated,  and  a  portion  of  the  thoracic  region  of  the 
spinal  cord  is  led  off  to  a  galvanometer,  a  persistent  negative  varia- 
tion followed  by  a  series  of  intermittent  variations  is  observed ;  this 
exactly  corresponds  to  the  tonic  spasm  followed  by  clonic  con- 
tractions which  occur  in  the  muscles  excited  by  this  means. 

The  galvanometer  in  the  hands  of  these  observers  also  proved  to 
be  a  valuable  instrument  for  determining  the  paths  taken  by  nervous 
impulses  in  the  cord.  One  example  will  suffice :  If  the  central  end 
of  one  sciatic  nerve  is  stimulated,  the  chief  electrical  variation  in  the 
cord  is  noticed  to  be  obtained  when  the  same  side  of  the  cord  is  led 
off  to  the  galvanometer,  but  a  certain  amount  of  electrical  variation 
is  obtainable  from  the  opposite  side  of  the  cord.  This  coincides  with 
the  fact  ascertained  by  other  methods,  that  the  main  sensory 
channel  is  on  the  same  side  of  the  cord  as  the  entering  nerves,  but 
that  there  is  a  certain  amount  of  decussation  below  the  level  of  the 
bulb. 

Electromotive  changes  also  occur  during  activity  in  the  cortex 
cerebri,  but  they  have  not  been  much  studied,  and  we  do  not  know 
whether  they  have  their  seat  in  the  grey  or  in  the  underlying  white 
matter. 


744  FUNCTIONS  OF  THE  CEREBRUM  [CH.  L. 

Sleep  and  Narcosis. 

The  conditions  that  favour  sleep  are  :— 

(1)  A  diminution  of  the  impulses  entering  the  central  nervous 
system   by   the   afferent    channels.     This   is   under   our  voluntary 
control,  as,  for  instance,  in  closing  the  eyes,  or  retiring  to  a  quiet 
room. 

(2)  Fatigue.      This    diminishes    the    readiness   of    the   central 
nervous  system  to  respond  to  stimuli. 

The  first  two  hours  of  sleep  are  always  the  most  profound ;  later 
on,  relatively  weak  stimuli  will  cause  awakening.  Of  the  parts  of 
the  central  nervous  system,  the  spinal  cord  is  always  less  profoundly 
affected  than  the  brain,  but  even  the  brain  is  never  entirely  irrespon- 
sive, and  unless  slumber  is  very  profound,  dreams  are  the  subjective 
result  of  external  stimuli.  Sensations  of  sound  appear  to  be  the 
last  to  disappear  as  sleep  comes  on,  and  the  first  to  be  realised 
on  awakening. 

Sleep  has  been  attributed  by  some  to  changes  in  the  blood-supply 
of  the  brain,  and  ultimately  referred  to  fatigue  of  the  vaso-motor 
centres.  The  existence  of  an  effective  vaso-motor  mechanism  in  the 
cerebral  blood-vessels  themselves  is  problematical  (see  p.  313);  so 
that  if  changes  occur  in  the  cerebral  blood-pressure  or  rate  of  flow, 
they  are  mainly  secondary  to  those  which  are  produced  in  other 
parts  of  the  body.  Plethysmographic  records  from  the  arm  of  a 
sleeping  man  show  a  diminution  in  its  volume  every  time  he  is 
disturbed,  even  though  the  disturbance  may  not  be  sufficient  to 
awaken  him.  This  is  interpreted  as  meaning  a  diminution  in  the 
blood  of  the  body,  and  a  corresponding  increase  in  the  blood-flow 
through  the  brain.  It  is,  however,  quite  possible  that  the  vascular 
condition  is  rather  the  concomitant  or  consequence  of  sleep  than  its 
cause.  Howell  among  others  believes  it  to  be  the  cause,  and  attributes 
the  sleepiness  that  follows  a  heavy  meal  to  the  mechanical  effect  of  a 
dilatation  of  the  abdominal  vessels  in  producing  a  diminished  blood- 
flow  through  the  brain ;  but  the  sleep  that  normally  comes  on  at  the 
end  of  the  day,  he  believes  to  be  produced  by  cerebral  anaemia  follow- 
ing dilatation  of  the  blood-vessels  of  the  skin,  such  dilatation  being 
due  to  vaso-motor  fatigue. 

Some  of  the  theories  to  account  for  sleep  have  been  chemical. 
Thus  certain  observers  have  considered  that  sleep  is  the  result  of  the 
action  of  chemical  materials  produced  during  waking  hours,  which 
have  a  soporific  effect  on  the  brain;  according  to  this  theory 
awakening  from  sleep  is  due  to  the  action  of  certain  other  materials 
produced  during  rest,  which  have  the  opposite  effect.  Obersteiner 
has  gone  so  far  as  to  consider  that  the  soporific  substances  are 
acid  in  nature,  and  others  regard  them  as  alkaloidal.  These  theories 


CH.  L.]  SLEEP   AND   NARCOSIS  745 

all  rest  upon  the  flimsiest  foundations,  and  none  has  yet  been  found 
to  stand  experimental  tests. 

Then  there  are  what  we  may  term  histological  theories  of  sleep, 
and  these  are  equally  unsatisfactory.  The  introduction  of  the  Golgi 
method  opened  a  fresh  field  for  investigators,  and  several  have 
sought  to  find  by  this  method  a  condition  of  the  neurons  produced 
by  narcotics  such  as  opium  and  chloroform,  which  is  different  from 
that  which  obtains  in  the  waking  state. 

Demoor  and  others  found  in  animals  in  which  deep  anaesthesia 
has  occurred,  that  the  dendrites  exhibit  moniliform  swellings,  that 
is,  a  series  of  minute  thickenings  or  varicosities.  On  the  strength 
of  this  observation,  what  we  may  call  a  biophysical  theory  of 
sleep  has  been  formulated ;  in  the  waking  state,  the  neighbouring 
nerve  units  are  in  contact  with  each  other ;  transmission  of  nerve 
impulses  from  neuron  to  neuron  is  then  possible,  and  the  result  is 
consciousness ;  during  sleep  the  dendrites  are  retracted  in  an 
amoeboid  manner ;  the  neurons  are  therefore  separated,  and  the  result 
is  unconsciousness. 

Lugaro,  on  the  other  hand,  takes  the  precisely  contrary  view. 
He  was  not  able  to  discover  moniliform  enlargements,  and  his  bio- 
physical  hypothesis  is  that  the  interlacing  of  dendrites  is  much  more 
intimate  during  sleep  than  during  consciousness.  He  therefore 
explains  sleep  by  supposing  that  the  definite  and  limited  relation- 
ships between  neurons  no  longer  exists,  but  are  lost  and  rendered 
ineffective  by  the  universality  of  the  connecting  paths.  It  is  not 
very  difficult  to  explain  such  divergence  of  views,  for  they  both 
depend  mainly  on  observations  made  by  a  single  method ;  and  the 
method  itself  is  open  to  objection.  It  is  one  which  gives  even  in  the 
same  brain  most  inconstant  results,  and  is  not  calculated  to  show 
much  more  than  an  outline  of  a  few  of  the  cells  and  their  branches. 

A  more  satisfactory  histological  investigation  of  the  effect  of 
anaesthetics  on  nerve-cells  was  carried  out  by  Hamilton  Wright. 

He  used  rabbits  and  dogs,  and  subjected  them  to  ether  and 
chloroform  narcosis  for  periods  varying  from  half  an  hour  to  nine 
hours.  In  both  animals  he  found  that  the  nerve-cells  are  affected, 
but  in  rabbits  much  more  readily.  This  accords  quite  well  with 
what  is  known  regarding  the  susceptibility  of  rabbits  as  compared  to 
dogs  towards  the  influence  of  these  narcotising  agents.  In  a  rabbit, 
the  nerve-cells,  especially  of  the  cerebrum,  show  changes  even  after 
only  half  an  hour's  anaesthesia,  but  in  dogs  at  least  four  hours'  anaes- 
thesia must  be  employed.  By  the  Golgi  method  the  moniliform 
enlargements  can  be  seen.  These  become  more  numerous,  larger, 
and  encroach  more  and  more  on  the  dendritic  stems,  the  longer  the 
anaesthesia  is  kept  up.  The  accompanying  illustrations  show  the 
appearances  seen  (fig.  457). 


74:6  FUNCTIONS    OF   THE   CEREBRUM  [CH.  L. 

Lugaro's  failure  to  find  these  appearances  is  doubtless  due  to  his 
not  having  maintained  the  anaesthesia  long  enough  in  his  dogs. 

Wright  started  his  work  with  a  bias  in  favour  of  Demoor's  bio- 
physical theory,  but  he  soon  found  that  the  theory  was  untenable ; 
the  results  of  his  observations  have  shown  him  that  the  action  of 
anaesthetics  is  biochemical  rather  than  biophysical,  and  he  has  been 
led  to  this  conclusion  by  the  employment  of  other  histological 
methods,  particularly  the  most  sensitive  one  we  possess,  namely,  the 
methylene-blue  reaction. 

Owing  to  the  chemical  action  of  the  anaesthetic  on  the  cells,  the 
Nissl  bodies  have  no  longer  an  affinity  for  methylene-blue,  and  the 
cells  consequently  present  what  Wright  calls  a  rarefied  appearance ; 


FIG.  457.— Mouiliform  enlargements  on  dendriles  of  nerve-cells,  rendered  evident  by  Cox's  modification 
of  Golgi's  method.  A,  in  a  cortical  cell  of  a  rabbit ;  B,  in  a  corresponding  cell  of  a  dog's  biain,  after 
six  hours'  ansesthetisation  with  ether  in  each  case.  (Hamilton  Wright.) 

when  this  becomes  marked  the  cells  appear  like  the  skeletons  of 
healthy  cells.  In  extreme  cases  the  cells  look  as  though  they  had 
undergone  a  degenerative  change,  and  after  eight  or  nine  hours' 
anaesthesia  in  dogs,  even  the  nucleus  and  nucleolus  lose  their  affinity 
for  basic  dyes.  The  change,  however,  is  not  a  real  degeneration,  and 
passes  off  when  the  drug  disappears  from  the  circulation.  Even 
after  nine  hours'  anaesthesia  the  cells  return  rapidly  to  their  normal 
condition,  stain  normally,  moniliform  enlargements  have  disappeared, 
and  no  nerve-fibres  show  a  trace  of  Wallerian  degeneration.  The 
pseudo-degenerative  change  produced  by  the  chemical  action  of  the 
anaesthetic  no  doubt  interferes  with  the  normal  metabolic  activity 
of  the  cell-body,  and  this  produces  effects  on  the  cell-branches.  In 


CH.  L.]  SLEEP   AND   NARCOSIS  747 

the  early  stages  of  Wallerian  degeneration,  the  branch  of  the  nerve- 
cell  which  we  call  the  axis-cylinder  presents  swellings  or  varicosi- 
ties,  produced  by  hydration  or  some  similar  chemical  change.  The 
monilif  orm  enlargements  seen  during  the  temporary  pseudo-degenera- 
tive effects  produced  by  anaesthetics  are  comparable  to  this.  These 
enlargements  are  therefore  not  the  primary  cause  of  loss  of  conscious- 
ness, but  are  merely  secondary  results  of  changes  in  the  cell-body. 
When  a  tree  begins  to  wither  the  earliest  apparent  change  is  noticed 
in  the  branches  most  remote  from  the  centre  of  nutrition,  the  root ; 
as  the  changes  in  the  centre  of  nutrition  become  more  profound,  the 
larger  branches  become  implicated,  but  the  seat  of  the  mischief  is 
not  primarily  in  the  branches.  This  illustration  may  serve  to  render 
intelligible  what  is  found  in  nerve-cells  and  their  branches. 

Moore  and  Eoaf  believe  that  the  substance  in  the  nerve-cells  (as 
well  as  the  other  cells  of  the  body)  which  is  affected  by  chloroform 
is  the  protein.  They  have  shown  that  unstable  compounds  of  protein 
and  chloroform  are  obtainable ;  hence  the  greater  solubility  of  chloro- 
form in  blood  than  in  water.  They  compare  the  chloroform-protein 
compound  to  oxyhaemoglobin,  for  it  undergoes  dissociation  in  the 
same  sort  of  way.  Just  as  oxyhaemoglobin  parts  with  its  oxygen  to 
the  tissue-cells,  so  the  chloroform  parts  company  from  the  blood- 
protein,  and  enters  into  combination  with  the  cell-protein,  limiting 
its  activity  and  producing  quiescence  or  anaesthesia.  When  the 
administration  of  the  chloroform  ceases,  the  tension  of  chloroform  in 
the  blood  is  no  longer  maintained,  so  the  combination  between  the 
cell-protein  and  chloroform  dissociates,  and  anaesthesia  passes  off. 

The  theory  which  has  met  with  most  favour  in  relation  to  anaes- 
thetics, however,  is  that  known  as  the  Meyer-Overton  hypothesis; 
this  theory,  which  has  received  abundant  confirmation  by  numerous 
observers,  points  out  that  the  cells  are  easily  permeable  to  the  vola- 
tile anaesthetics  owing  to  the  presence  of  fat  and  lipoid  material  in 
their  plasmatic  membrane  (see  p.  330).  It  can  hardly  now  be 
doubted  that  the  solubility  of  the  volatile  anaesthetics  in  the  lipoids 
of  the  membrane  (or,  what  comes  to  the  same  thing,  the  solubility  of 
the  lipoids  in  the  anaesthetic)  is  an  important  factor  in  anaesthesia ; 
the  anaesthetic  thus  enters  the  cell  easily,  and  throws  the  lipoid  con- 
stituents of  the  protoplasm  (and  perhaps  secondarily  the  protein 
constituents  also)  out  of  gear,  the  net  result  being  a  lessening  of  the 
oxidative  changes  which  are  essential  in  active  vital  processes. 

The  volatile  anaesthetics,  and  especially  chloroform,  are  dangerous 
drugs,  and  although  their  discovery  is  one  of  the  greatest  blessings 
to  suffering  humanity,  and  in  experiments  on  animals,  means  should 
be  adopted  for  preventing  the  fatalities  which  are  even  now  too 
frequent.  It  is  specially  needful  that  anaesthetists  should  not 
administer  the  drug  in  a  haphazard  way,  but  take  care  that  the  amount 


748  FUNCTIONS  OF  THE  CEREBRUM  [CH.  L. 

of  chloroform  in  the  inspired  air  should  never  rise  over  2  per  cent. ; 
smaller  percentages  may  be  employed  when  once  the  patient  is  under 
the  influence  of  the  drug.  There  have  been  several  instruments 
invented  (by  Waller  and  others)  by  means  of  which  the  concentration 
of  the  chloroform  given  can  be  easily  measured. 

But  the  artificial  sleep  of  a  deeply-narcotised  animal  is  no  criterion 
of  what  occurs  during  normal  sleep.  The  sleep  of  anaesthesia  is  a 
pathological  condition  due  to  the  action  of  a  poison.  The  drug 
reduces  the  chemico-vital  activities  of  the  cells,  and  is,  in  a  sense, 
dependent  on  an  increasing  condition  of  exhaustion,  which  may  culmi- 
nate in  death.  Natural  sleep,  on  the  other  hand,  is  the  normal  mani- 
festation of  one  stage  in  the  rhythmical  activity  of  nerve-cells,  and 
though  it  may  be  preceded  by  fatigue  or  exhaustion,  it  is  accom- 
panied by  repair,  the  constructive  side  of  metabolic  activity.  This 
is  true  for  many  other  organs  in  addition  to  the  central  nervous 
system ;  sleep  is  a  time  of  repose  for  them  also,  but  the  amount  of 
rest  varies ;  the  voluntary  muscles,  except  those  concerned  in  breath- 
ing, will  rest  most,  but  the  heart  continues  to  beat,  the  urine  is  still 
being  secreted,  the  processes  of  digestion  go  on,  so  that  for  such 
organs  activity  is  only  diminished. 

It  should  be  recognised  by  the  public  that  sleep  is  the  period  of 
anabolism,  repair  and  growth,  and  a  large  allowance  is  therefore 
necessary  in  growing  children.  The  mistaken  Spartan  discipline  of 
certain  parents  and  schoolmasters  in  insisting  upon  a  short  period  of 
repose  often  does  incalculable  harm  both  mental  and  physical  to 
those  under  their  charge.  When  in  the  children  of  the  poorer  classes, 
early  rising  for  the  purpose  of  earning  a  miserable  pittance  is  com- 
bined with  late  hours  of  retiring  to  rest,  and  with  the  discomforts  of 
crowded  bedrooms,  and  crowded  beds  which  render  real  rest  impos- 
sible, the  damage  done  is  greater  still,  and  is  one  cause  of  physical 
deterioration.  Many  children  judged  to  be  "defective"  are  really 
only  suffering  from  want  of  sleep. 

Loss  of  sleep  is  more  damaging  than  starvation.  Dogs  will  recover  after  being 
starved  for  three  weeks,  but  they  die  from  loss  of  sleep  in  five  days.  The  body 
temperature  falls,  reflexes  disappear,  and  post-mortem  the  brain  is  found  to  contain 
capillary  haemorrhages,  the  cord  is  dry  and  anaemic,  and  fatty  degeneration  is  found 
in  most  of  the  tissues. 

In  man,  loss  of  sleep  curiously  enough  causes  a  slight  rise  in  weight ;  the  body 
temperature  falls  ;  the  excretion  of  nitrogen  and  still  more  so  that  of  phosphoric  acid 
increases ;  the  reactions  of  the  muscular,  and  later  those  of  the  nervous,  system 
diminish  in  intensity,  except  that  in  all  cases  there  is  an  increase  in  acuteness  of 
vision.  These  experiments  were  made  by  Patrick  and  Gilbert  on  three  young  men, 
who  voluntarily  went  without  sleep  for  ninety  hours.  At  the  end  of  the  experiment 
a  very  small  extra  amount  of  sleep  beyond  the  normal  caused  complete  restoration, 
and  all  the  symptoms,  including  the  increase  of  weight,  disappeared. 

The  sleep  produced  by  hypnotic  suggestion  differs  from  ordinary  sleep.  But 
exact  knowledge  of  the  phenomena  of  this  kind  of  sleep  is  at  present  lacking. 


CHAPTEE  LI 

FUNCTIONS  OF  THE  CEREBELLUM 

IN  past  times  there  have  been  several  views  held  as  to  the  functions 
of  the  cerebellum.  One  of  the  oldest  of  these  was  the  idea  that  the 
cerebellum  was  associated  with  the  function  of  generation ;  another 
view,  first  promulgated  by  WilUs,  was  that  the  cerebellum  contained 
the  centres  which  regulate  the  functions  of  organic  life ;  this  arose 
from  the  circumstance  that  diseases  of  the  cerebellum  are  often 
associated  with  nausea  and  vomiting;  it  is  a  familiar  fact  that  in 
displacements  of  equilibrium  such  as  occur  on  board  ship  in  a  rough 
sea,  or  in  the  disease  called  Meniere's  disease,  sickness  is  a  frequent 
result;  it  appears  from  this  that  the  cerebellum  does  receive 
certain  impulses  from  the  viscera.  The  third  and  last  of  these 
older  theories  was  that  the  cerebellum  was  the  centre  for  sensation. 
This  arose  from  the  fact  that  certain  of  the  afferent  channels  of  the 
spinal  cord  were  traced  into  the  cerebellum.  The  impulses  that  travel 
along  these,  however,  though  afferent,  are  not  truly  sensory,  and  their 
reception  in  the  cerebellum  is  not  associated  with  consciousness. 

The  true  function  of  the  cerebellum  was  first  pointed  out  by 
Flourens,  who  showed  that  the  cerebellum  is  the  great  centre  for  the 
coordination  of  muscular  movement,  and  especially  for  that  variety 
of  coordination  which  is  called  equilibration — that  is,  the  harmonious 
adjustment  of  the  working  of  the  muscles  which  maintain  the  body 
in  a  position  of  equilibrium. 

It  must  not  be  supposed  from  this  that  the  cerebellum  is  the  sole 
centre  for  coordination.  We  have  already  seen  that  all  the  machinery 
necessary  for  carrying  out  very  complicated  locomotive  movements 
is  present  in  the  spinal  cord.  The  higher  centres  set  this  machinery 
going,  and  the  work  of  arranging  what  muscles  are  to  act,  and  in 
what  order,  is  carried  out  by  the  whole  of  the  grey  matter  from  the 
corpora  striata  to  the  end  of  the  spinal  cord,  including  such  out- 
growths as  the  corpora  quadrigemina  and  cerebellum.  An  instance 
of  a  complex  coordinated  movement  is  seen  in  what  we  learnt  to  call 
in  the  last  chapter  conjugate  deviation  of  head  and  eyes.  The  higher 
cortical  centre  gives  the  general  word  of  command  to  turn  the  head 

749 


750  FUNCTIONS  OF  THE  CEREBELLUM          [CH.  LL 


and  eyes  to  the  right  :  the  subsidiary  centres  or  subordinate  officials 
arrange  that  this  is  to  be  accomplished  by  the  external  rectus  of  the 
right  eye  supplied  by  the  right  sixth  nerve,  the  internal  rectus  of  the 
left  eye  supplied  by  the  left  third  nerve,  and  numerous  muscles  of 
neck  and  back  of  both  sides  supplied  by  numerous  nerves.  The 
relaxation  of  the  antagonistic  muscles  has  also  to  be  provided  for. 
We  thus  see  how  the  complicated  intercrossing  of  fibres  and  connec- 
tions of  the  centres  of  the  various  nerves  are  brought  into  play. 

The  functions  of  the  cerebellum  are  investigated  by  the  same  two 
methods  of  experiment  (stimulation  and  extirpation)  which  are 
employed  in  similar  researches  on  the  cerebrum.  The  anatomical 
connections  of  the  cerebellum  with  other  parts  of  the  cerebro-spinal 
axis  by  its  three  peduncles  have  been  already  considered  on  p.  684. 


FIG.  458.— Pigeon  after  removal  of  the  cerebellum.    (Dalton.) 

In  some  of  the  lower  animals  the  vermis  is  practically  the 
only  part  of  the  cerebellum  which  is  present,  and  it  is  this  part  of 
the  cerebellum  which  is  principally  concerned  in  the  coordination 
of  the  bodily  movements.  The  cerebellar  hemispheres  are  especi- 
ally connected  with  the  opposite  cerebral  hemispheres;  and  just 
as  the  different  regions  of  the  body  have  corresponding  areas  in  the 
cerebrum,  so  also  they  are  similarly  represented  in  the  cerebellum ; 
but  it  does  not  appear  necessary  from  the  practical  standpoint  to  go 
here  into  the  scanty  and  disputed  details  of  cerebellar  localisation 
already  discovered. 

If  the  cerebellum  is  removed  in  an  animal,  or  if  it  is  the  seat  of 
disease  in  man,  the  result  is  a  condition  of  slight  muscular  weak- 
ness ;  but  the  principal  symptoms  observed  are  loss  of  muscular  tonus 
and  a  condition  of  incoordination,  chiefly  evidenced  by  a  staggering  gait 
similar  to  that  seen  in  a  drunken  man.  It  is  called  cerebellar  ataxy. 

This  condition  is  well  illustrated  in  the  figure  (fig.  458);   the 


CH.  LI.]  FUNCTIONS  OF  THE  CEREBELLUM  751 

disturbed  condition  of  the  animal  contrasts  very  forcibly  with  the 
sleepy  state  produced  by  removal  of  the  cerebrum  (see  fig.  446,  p.  723). 

In  order  that  the  cerebellum  may  duly  execute  its  function  of 
equilibration,  it  is  necessary  that  it  should  send  out  impulses ;  this  it 
does  by  fibres  that  leave  its  cells  and  pass  out  through  its  peduncles ; 
they  pass  out  to  the  opposite  cerebral  hemisphere,  and  so  influence 
the  discharge  of  the  impulses  from  the  cortex  of  the  cerebrum. 
Impulses  also  pass  out  to  the  cord  (see  p.  685),  but  the  exact  course  of 
some  of  the  descending  tracts  has  still 
to  be  worked  out. 

The  cerebellum  thus  acts  upon  the 
muscles  of  the  same  side  of  the  body 
in  conjunction  with  the  cerebral  hemi- 
sphere of  the  opposite  side.  The  close 
inter-relation  of  one  cerebral  with  the 
opposite  cerebellar  hemisphere  is  shown 
in  cases  of  brain  disease,  in  which 
atrophy  of  one  cerebellar  hemisphere 
follows  that  of  the  opposite  cerebral 

Vi Arm Qr»Vi pr A    fopft    firr     A^Q^  Fm.  459. — This  is  a  reproduction  of  a 

nemiSpner  3    (8Q(     ng.    40y;.  photograph  of  a  lunatic's  brain  lent 

In     Order     that     the    Cerebellum    may  me  by  Dr  Fricke.    One  cerebral  and 

,-,  .                      .,      •  the  opposite   cerebellar   hemisphere 

Send     OUt     impulses     in     thlS     Way,    it     IS  are  atrophied. 

necessary  that  it  receive  impulses  which 

guide  it  by  keeping  it  informed  of  the  position  of  the  body  in  space. 
These  impulses,  we  have  already  insisted,  though  afferent  are  non- 
sensory;  they  travel  by  paths  which  at  the  start,  however,  are 
offshoots  from  those  which  carry  the  real  sensory  impulses  to  the 
cerebrum.  These  afferent  impulses  originate  from  or  are  associated 
with  the  impulses  which  in  the  cerebrum  produce  sensations  of  the 
four  following  kinds : — 

1.  Tactile.  3.  Visual. 

2.  Motorial.  4.  Labyrinthine. 

1.  Tactile  impressions. — The  importance  of  the  tactile  sense  is 
obvious ;  and  in  diseases  of  the  afferent  tracts,  loss  of  that  sense  in 
the  lower  limbs  leads  to  disturbances  of  equilibrium ;  in  such  cases 
a  man  has  difficulty  in  balancing  himself  while  standing  with  his 
eyes   shut.     Sherrington,  however,  has   shown   how   comparatively 
unimportant  is  the  loss  of  tactile  sensibility  from  the  feet.     A  cat, 
in  which  the  feet  have  been  completely  desensitised  by  division  of 
all  their  nerves,  can  stand  and  walk  without  obvious  inconvenience. 
It  is  not  until  the  sensitiveness  of  the  joints,  especially  in  the  upper 
segments  of  the  limb,  is  interfered  with  that  marked  disturbances 
of  balance  are  noticeable. 

2.  Material*  impressions. — Another  important  sense  is  that  which 


752 


FUNCTIONS  OF  THE  CEKEBELLUM 


[CH.  LI. 


enables  us  to  know  what  we  are  doing  with  our  muscles.  Sensory 
fibres  pass  from  the  muscles,  and  their  tendons  to  the  posterior  roots 
of  the  spinal  nerves,  and  the  impulses  ascend  the  sensory  tracts 
through  cord -and  brain  to  reach  the  ascending  parietal  convolution. 
Their  offshoots,  which  carry  the  non-sensory  impulses  to  the  cere- 
bellum, reach  it  via  Clarke's  column  and  the  cerebellar  tracts.  In 
many  cases  of  locomotor  ataxy  there  is  but  little  loss  of  tactile 
sensibility,  and  the  condition  of  incoordination  is  then  chiefly  due  to 

the  loss  of  impressions  from  motorial 
organs  (muscles  and  joints). 

3.  Visual  impressions. — The  use  of 
visual  impressions  in  guiding  the 
nervous  centres  for  the  maintenance 
of  equilibrium  is  seen  in  those  cases 
of  locomotor  ataxy  where  there  is  loss 
of  equilibrium  when  the  patient  closes 
his  eyes.  Destruction  of  the  eyes  in 
animals  often  causes  them  to  spin 
round  and  lose  their  balance.  The 
giddiness  experienced  by  many  people 
on  looking  at  moving  water,  or  after 
the  onset  of  a  squint,  or  when  objects 
are  viewed  under  unusual  circum- 
stances, as  in  the  ascent  of  a  mountain 
railway,  is  due  to  the  same  thing.  The 
importance  of  keeping  one's  eyes  open 
is  brought  home  to  one  very  forcibly 
when  one  is  walking  in  a  perilous  posi- 
tion, as  along  the  edge  of  a  precipice, 
where  an  upset  of  the  equilibrium 
would  be  attended  with  serious  con- 
sequences. Under  more  ordinary  cir- 
cumstances, the  non-sensory  visual  offshoots  which  enter  the  cere- 
bellum are  sufficient  to  maintain  equilibrium.  In  speaking  of  visual 
impressions  it  should  be  understood  that  these  in  themselves  are  not 
the  actual  guide.  It  is  the  projection  of  what  is  seen  in  relation  to 
the  position  of  the  body  (ascertained  by  the  innervation  of  the  head 
muscles  and  ocular  muscles)  that  is  the  chief  guide. 

4.  Labyrinthine  impressions. — These  are  the  most  important  of 
all ;  they  are  the  impressions  that  reach  the  central  nervous  system 
from  that  part  of  the  internal  ear  called  the  labyrinth,  and  in  this 
case  the  sensory  element  is  subordinate  to  the  non-sensory.  Here, 
however,  we  must  pause  to  consider  some  anatomical  facts  in 
connection  with  the  semicircular  canals  that  make  up  the  labyrinth. 
Fig.  460  is  an  external  view  of  the  internal  ear ;  it  is  enclosed  within 


FIG.  460.— Right  bony  labyrinth,  viewed 
from  the  outer  side.  The  specimen 
here  represented  was  prepared  by 
separating  piecemeal  the  looser  sub- 
stance of  the  petrous  bone  from  the 
dense  walls  which  immediately  en- 
close the  labyrinth.  1,  the  vestibule; 
2,  fenestra  ovalis;  3,  superior  semi- 
circular canal ;  4,  horizontal  or  ex- 
ternal canal ;  5,  posterior  canal ;  *, 
ampullae  of  the  semicircular  canals ; 
6,  first  turn  of  the  cochlea ;  7,  second 
turn;  8,  apex;  9,  feriestra  rotunda. 
The  smaller  figure  in  outline  below 
shows  the  natural  size.  (Sommering.) 


CH.  LI.] 


LABYRINTHINE    IMPRESSIONS 


753 


the  petrous  portion  of  the  temporal  bone;  and  consists  of  three 
parts — the  vestibule  (1),  the  three  semicircular  canals  (3,  4,  5)  which 
open  into  the  vestibule,  and  the  tube,  coiled  like  a  snail's  shell,  called 
the  cochlea  (6,  7,  8).  The  cochlea  is  the  part  of  the  apparatus  which 
is  concerned  in  the  reception  of  auditory  impressions ;  it  is  supplied 
by  the  cochlear  division  of  the  eighth  or  auditory  nerve.  The 
remainder  of  the  internal  ear  is  concerned  not  in  hearing,  but  in 
the  reception  of  the  impressions  we  are  now  studying;  it  is  sup- 
plied by  the  vestibular  division  of  the  eighth  nerve.  Within  the 
vestibule  are  two  chambers  made  of  membrane,  called  the  utricle 
and  the  saccule;  these  com- 
municate with  one  another  and 
with  the  canal  of  the  cochlea. 
Within  each  bony  semicircular 
canal  is  a  membranous  semi- 
circular canal  of  similar  shape. 
Each  canal  is  filled  with  a 
watery  fluid  called  endolymph, 
and  separated  from  the  bony 
canal  by  another  fluid  called 
perilymph.  Each  canal  has  a 
swelling  at  one  end  called  the 
ampulla.  The  membranous 
canals  open  into  the  utricle; 
the  horizontal  canal  by  each  of 
its  ends ;  the  superior  and  pos- 
terior vertical  canals  by  three 
openings,  these  two  canals  being 
connected  at  their  non-ampul- 
lary  ends. 

Fig.  461  shows  in  transverse  section  the  way  in  which  the 
membranous  is  contained  within  the  bony  canal ;  the  membranous 
canal  consists  of  three  layers,  the  outer  of  which  is  fibrous  and 
continuous  with  the  periosteum  that  lines  the  bony  canal ;  then  comes 
the  tunica  propria,  composed  of  homogeneous  material,  and  thrown 
into  papillae  except  just  where  the  attachment  of  the  membranous  to 
the  bony  canal  is  closest ;  and  the  innermost  layer  is  a  somewhat 
flattened  epithelium. 

At  the  ampulla  there  is  a  different  appearance;  the  tunica 
propria  is  raised  into  a  hillock  called  the  crista  acoustica  (see  fig.  462) ; 
the  cells  of  the  epithelium  become  columnar  in  shape,  and  to  some 
of  them  fibres  of  the  eighth  nerve  pass,  arborising  round  them ; 
these  cells  are  provided  with  stiff  hairs,  which  project  into  what  is 
called  the  cupula,  a  mass  of  mucus-like  material  containing  otoliths 
or  crystals  of  calcium  carbonate.  Between  the  hair-cells  are  fibre- 

3  B 


FIG.  461.— Section  of  human  semicircular  canal. 
(After  Riidinger.)  1,  Bone;  2,  periosteum  ;  3,  3, 
fibrous  bands  connecting  the  periosteum  to  4,  the 
outer  fibrous  coat  of  the  membranous  canal; 
5,  tunica  propria ;  6,  epithelium. 


754 


FUNCTIONS  OF  THE  CEREBELLUM 


[CH.  LI. 


cells  which  act  as  supports  (fig.  463).     When  the  endolymph  in  the 
interior  of  the  canals  is  thrown  into  vibration,  the  hairs  of  the  hair- 


Fio.  462. — Section  through  the  wall  of  the  ampulla  of  a  semicircular  canal,  passing  through  the  crisia 
acoustica.  1,  Epithelium ;  2,  tunica  propria  ;  3,  fibrous  layer  of  canal ;  N,  bundles  of  nerve-fibres  ; 
C,  cupula,  into  which  the  hairs  of  the  hair-cells  project.  (After  Schiifer.) 

cells  are  affected,  and  a  nervous  impulse  is  set  up  in  the  contiguous 
nerve-fibres,  which  carry  it  to  the  central  nervous  system. 

The  walls  of  the  saccule  and 
utricle  are  similar  in  composition, 
and  each  has  a  similar  hillock,  called 
a  macula,  to  the  hair-cells  on  which 
nerve-fibres  of  the  vestibular  nerve 
are  distributed. 

It  will  be  noticed  that  the  canals 
of  each  side  are  in  three  planes  at 
right  angles  to  each  other,  and  we 
learn  the  movements  of  our  body 
with  regard  to  the  three  dimensions 
of  space  by  means  of  impressions 
from  the  ampullary  endings  of  the 
vestibular  nerve;  these  impressions 
are  set  up  by  the  varying  pressure  of 
the  endolymph  in  the  ampullae. 

Thus  a  sudden  turning  of  the 
head  from  right  to  left  will  cause 
movement  of  the  endolymph  towards, 
and  therefore  increased  pressure  on, 
the  hair-cells  connected  to  the  am- 
pullary nerve-endings  of  the  left  horizontal  canal,  and  diminished 
pressure  on  the  corresponding  apparatus  of  the  right  side.  It 
is  probable  that  resulting  from  such  a  movement  two  impulses 
reach  the  brain,  one  the  effect  of  increased  pressure  in  one  ampulla, 
the  second  the  effect  of  decreased  pressure  in  its  fellow.  It  may 


FIG.  463.— 1,  Hair-cell ;  3,  hair-cell,  showing 
the  hair  broken,  and  the  base  of  the  hair 
split  into  its  constituent  fibrils;  2,  fibre- 
cell;  N,  bundle  of  nerve-tibres  which 
have  lost  their  medullary  sheath,  and 
terminate  by  arborising  round  the  base 
of  the  hair-cells  ;  A  B,  surface  of  tunica 
propria.  (After  Retxius.) 


CH.  LL] 


THE   SEMICIRCULAR   CANALS 


755 


even  be  that  increased  pressure  on  one  side  of  a  crista  is  accompanied 
by  diminished  pressure  on  the  opposite  face  of  the  same  crista. 

"One  canal  can  be  affected  by,  and  transmit  the  sensation  of 
rotation  about  one  axis  in  one  direction  only;  and  for  complete 
perception  of  rotation  in  any  direction  about  any  axis,  six  canals  are 
required  in  three  pairs,  each  pair  being  in  the  same  or  parallel  planes, 
and  their  ampullae  turned  opposite  ways.  Each  pair  would  thus  be 
sensitive  to  any  rotation  about  a  line  at  right  angles  to  its  plane  or 
planes,  the  one  canal  being  influenced  by  rotation  in  one  direction, 
the  other  by  rotation  in  the  opposite  direction."  (Crum-Brown.) 

The  two  horizontal  canals  are  in  the  same  plane ;  the  posterior 
vertical  of  one  side  is  in  a  plane  parallel  to  that  of  the  superior 
vertical  of  the  other  side  (see  fig.  464). 


FIG.  464. — Diagram  of  semicircular  canals,  to  show  their  positions  in  three  planes  at  right  angles  to 
each  other.  It  will  be  seen  that  the  two  horizontal  canals  (H)  lie  in  the  same  plane  :  and  that  the 
superior  vertical  of  one  side  (S)  lies  in  a  plane  parallel  to  that  of  the  posterior  vertical  (P)  of  the 
other.  (The  student  will  understand  that  though  in  the  diagram  the  canals  are  entirely  separated 
from  one  another,  that  they  are  really  connected,  as  shown  in  fig.  460.)  (After  Ewald.) 

When  these  canals  are  diseased  in  man  as  in  Meniere's  disease, 
there  are  disturbances  of  equilibrium :  a  feeling  of  giddiness,  which 
may  lead  to  the  patient's  falling  down,  is  associated  with  nausea  and 
vomiting.  In  animals  similar  results  are  produced  by  injury,  and  the 
subject  has  been  chiefly  worked  out  on  birds  by  Flourens,  where  the 
canals  are  large  and  readily  exposed,  and  more  recently  in  fishes,  by  Lee. 

Thus,  if  the  horizontal  canal  is  divided  in  a  pigeon,  the  head  is 
thrown  into  a  series  of  oscillations  in  a  horizontal  plane,  which  are 
increased  by  section  of  the  corresponding  canal  of  the  opposite  side. 
After  section  of  the  vertical  canals,  the  forced  movements  are  in  a 
vertical  plane,  and  the  animal  tends  to  turn  somersaults. 

"When  the  whole  of  the  canals  are  destroyed  on  both  sides 
the  disturbances  of  equilibrium  are  of  the  most  pronounced  character. 
Goltz  describes  a  pigeon  so  treated  which  always  kept  its  head  with 
the  occiput  touching  the  breast,  the  vertex  directed  downwards,  with 
the  right  eye  looking  to  the  left  and  the  left  looking  to  the  right, 
the  head  being  incessantly  swung  in  a  pendulum-like  manner. 
Cyon  says  it  is  almost  impossible  to  give  an  idea  of  the  perpetual 


756  FUNCTIONS  OF  THE  CEREBELLUM  [CH.  LI. 

movements  to  which  the  animal  is  subject.  It  can  neither  stand, 
nor  lie  still,  nor  fly,  nor  maintain  any  fixed  attitude.  It  executes 
violent  somersaults,  now  forwards,  now  backwards,  rolls  round  and 
round,  or  springs  in  the  air  and  falls  back  to  recommence  anew.  It 
is  necessary  to  envelop  the  animals  in  some  soft  covering  to  prevent 
them  dashing  themselves  to  pieces  by  the  violence  of  their  move- 
ments, and  even  then  not  always  with  success.  The  extreme 
agitation  is  manifest  only  during  the  first  few  days  following  the 
operation,  and  the  animal  may  then  be  set  free  without  danger ;  but 
it  is  still  unable  to  stand  or  walk,  and  tumultuous  movements  come 
on  from  the  slightest  disturbance.  But  after  the  lapse  of  a  fortnight 
it  is  able  to  maintain  its  upright  position.  At  this  stage  it  resembles 
an  animal  painfully  learning  to  stand  and  walk.  In  this  it  relies 
mainly  on  its  vision,  and  it  is  only  necessary  to  cover  the  eyes  with 
a  hood  to  dispel  all  the  fruits  of  this  new  education,  and  cause  the 
reappearance  of  all  the  motor  disorders."  (Ferrier.) 

It  is  these  canals  which  enable  all  of  us  to  know  in  which  direc- 
tion we  are  being  moved,  even  though  our  eyes  are  bandaged,  and 
the  feet  are  not  allowed  to  touch  the  ground.  On  being  whirled 
round,  such  a  person  knows  in  which  direction  he  is  being  moved, 
and  feels  that  he  is  moving  so  long  as  the  rate  of  rotation  varies, 
but  when  the  whirling  stops  he  seems,  especially  if  he  opens  his 
eyes,  to  be  whirling  in  the  opposite  direction,  probably  owing  to  the 
rebound  of  the  fluid  in  the  canals.  The  forced  movements  just 
described  in  animals  are  due  both  to  the  absence  of  the  normal  sensa- 
tions from  the  canals  and  to  delusive  sensations  arising  from  their 
irritation,  and  the  animal  makes  efforts  to  correct  the  movement 
which  it  imagines  it  is  being  subjected  to. 

Artificial  stimulation  of  the  canals  produces  movements  of  the  head  and  orbits, 
and  giddiness.  Similar  movements  occur  during  bodily  rotation,  and  giddiness  is 
the  result  of  a  rivalry  of  sensations  which  afford  conflicting  ideas  of  the  position  of 
the  body  relatively  to  external  objects.  A  certain  proportion  of  deaf  mutes  lose  their 
sense  or  direction  under  water,  cannot  maintain  their  equilibrium  when  their  eyes  are 
shut,  exhibit  no  orbital  movements  when  rotated,  and  never  suffer  from  sea-sickness 
or  giddiness.  This  proportion  is  approximately  the  frequency  in  which  abnormal 
conditions  of  the  canals  have  been  found  post-mortem  in  deaf  mutes. 

Section  and  stimulation  of  the  inferior  cerebellar  peduncles  (the  path  by  which 
the  vestibular  fibres  reach  the  cerebellum,  see  p.  682)  cause  incoodination,  chiefly 
evidenced  by  rotatory  and  circus  movements  similar  to  those  that  occur  when  the 
nerve-endings  in  the  semicircular  canals  are  destroyed  or  stimulated.  Stimulation 
of  the  cerebellum  itself— and  this  has  been  done  through  the  skull  in  man— causes 
giddiness,  and  consequent  muscular  efforts  to  correct  it.  The  results  of  stimulation, 
indeed,  are  precisely  analogous  to  those  of  extirpation,  only  in  the  reverse  direction. 
Loss  of  muscular  tone  which  follows  extirpation  of  the  canals  is  probably  the  result 
of  secondary  changes  in  the  brain. 


CHAPTER  LIT 

THE  PHYSIOLOGY  OF   CONSCIOUS   STATES 

THERE  are  certain  considerations,  relating  to  the  physiology  of  con- 
scious states  in  general,  to  which  it  will  be  well  to  pay  attention, 
before  we  pass  to  a  detailed  study  of  the  special  senses. 

It  is  sometimes  argued  that  states  of  consciousness  are  the 
product  of  the  activity  of  nerve-cells,  just  as  bile  is  the  product  of 
the  activity  of  the  liver-cell,  or  as  contraction  results  from  the 
activity  of  the  muscle  fibre.  But  this  analogy  will  not  bear  close 
investigation.  It  is,  however,  true  : — 

(1)  That  the  different  senses  are  dependent  for  their  manifesta- 
tion on  the  integrity  of  different  definitely  localisable  areas  of  the 
cerebral  cortex. 

(2)  That  such  drugs  as  alcohol,  caffein,  and  chloroform,  which 
have  a  known  action  on  living  substance,  also  affect  the  course  of 
conscious  processes. 

(3)  That  disease  or  malformation  of  the  brain  is  accompanied  by 
impairment  or  absence  of  intelligence. 

But  because  nervous  substance  is  essential  for  the  manifestation 
of  conscious  states,  one  cannot  legitimately  infer  that  this  substance 
produces  those  states.  Indeed,  by  a  vast  number  of  philosophers  a 
very  different  position  has  been  upheld.  So  far  from  believing  that 
mind  results  from  the  activity  of  living  matter,  they  have  insisted 
that  all  matter,  living  and  lifeless,  results  from  the  activity  of  mind. 
They  maintain  that,  were  it  not  for  mental  activity,  there  would  be 
no  conception,  nay  not  even  existence,  of  those  qualities  (e.g.,  sound, 
colour,  force,  weight,  hardness)  of  which  our  non-mental  world  of 
matter  is  composed. 

There  is  no  difficulty  in  accepting  the  statement  that  bile  is 
secreted  by  the  liver ;  in  this  case  the  product  is  physical,  and  it  is 
produced  by  physiological  (i.e.,  presumably,  by  chemical  and  physical) 
conditions.  On  the  other  hand,  if  we  state  that  consciousness  is 
secreted  by  the  brain,  we  are  linking  together  two  sets  of  phenomena, 
the  psychical  and  the  physiological,  between  which  a  connection  is 
inconceivable. 


757 


758  THE  PHYSIOLOGY  OF  CONSCIOUS   STATES  [CH.  LII. 

Consequently,  instead  of  stating  that  physiological  activity  is  the 
cause  of  mental  (or  psychical)  activity,  it  is  more  satisfactory  to 
assume  that  the  two  activities  run  parallel  with  one  another,  and  to 
recognise  that  the  nature  of  their  relation  is  unknown.  This  con- 
ception of  psycho-physical  parallelism  affords  the  physiologist  by  far 
the  best  working  hypothesis. 

It  leaves  unanswered  the  great  question  whether  brain  ever  acts 
on  mind,  or  mind  on  the  brain — which  of  the  two  is  the  master  or 
the  servant  of  the  other.  It  merely  implies  that  a  change  in  nerve 
substance  underlies  every  psychical  change ;  and  it  bids  the  physio- 
logist investigate  the  functions  of  the  nervous  system,  and  determine 
what  structures  are  called  into  activity  in  the  development  of 
various  conscious  states. 

We  must  recognise  that,  however  completely  we  may  one  day 
have  mapped  out  the  functions  of  the  various  parts  of  the  brain,  we 
shall  nevertheless  not  have  approached  a  step  nearer  towards  under- 
standing the  relation  between  the  data  of  physiological  and  psychical 
activity.  If  we  knew  the  function  of  every  nerve  cell  of  the  body, 
the  gap  between  the  material  and  the  mental  would  not  be  a  bit  less 
wide.  Just  as  a  ray  of  light  cannot  see  itself,  so  we  cannot  expect 
to  understand  states  of  consciousness  from  a  mere  study  of  cerebral 
function. 

It  is  therefore  imperative  to  avoid  confusion  between  the  two 
aspects  involved  in  this  psycho-physical  parallelism.  The  psychical 
is  one  language,  the  physical  (i.e.  the  physiological)  is  another; 
and  the  two  vocabularies  must  be  kept  distinct  from  one  another. 
Psychology  and  physiology  stand  in  the  relation  of  an  object  and 
its  mirrored  reflection.  To  confound  object  and  image — to  speak,  for 
instance,  of  a  sensation  (instead  of  an  impulse)  being  transmitted 
along  a  nerve-fibre,  is  to  blur  and  to  confuse  two  distinct  sciences. 

The  psychologist  distinguishes  three  modes  in  which  conscious- 
ness is  manifested.  These  are  (1)  the  cognitive,  (2)  the  affective, 
and  (3)  the  conative  modes.  Through  the  cognitive  mode  we  become 
aware  of  the  object  thought  of.  Owing  to  the  affective  mode,  our 
state  of  consciousness  is  toned  with  pleasure,  indifference,  or  dis- 
pleasure. The  conative  mode  manifests  itself  as  a  striving  or  "  felt 
tendency"  towards  an  end.  In  every  state  of  consciousness  these 
three  modes  are  present,  but  their  relative  prominence  is  always 
different.  For  example,  in  perception,  in  memory,  or  imagination,  the 
cognitive  element  is  to  the  fore;  in  love,  sorrow,  or  doubt,  the 
affective  element  predominates ;  while  in  intense  desire,  the  conative 
element  is  most  easily  recognisable.  Into  the  physiology  of  affection 
and  conation  we  shall  not  enter  here.  They  receive  adequate  atten- 
tion in  books  devoted  to  physiological  and  experimental  psychology. 
But  a  conscious  state  implies  also  a  contrast  between  what  is 


CH.  LII.]  THE    PHYSIOLOGY   OF   CONSCIOUS    STATES  759 

outside  of  ourselves  (the  object)  and  our  feelings  and  strivings  in 
connection  with  it,  which  are  spoken  of  as  subjective.  The  existence 
of  this  "  subject-object  relation  "  implies  the  activity  of  an  Ego,  who 
experiences  conscious  states,  who  is  cognisant,  feels  or  strives. 
Indeed  no  state  of  consciousness  is  ever  possible,  unless  experienced 
by  the  Ego.  In  becoming  manifest,  it  blends  with  the  Ego,  and  is 
modified  or  rather  determined  by  the  Ego's  previous  experiences ; 
and  in  turn  it  modifies  the  Ego.  Thus  the  Ego  everlastingly  moulds 
and  is  itself  moulded  by  its  own  states  of  consciousness  or 
experiences.  Consequently,  states  of  consciousness  are  not  inde- 
pendent units.  The  mind,  like  its  physiological  correlate,  the  central 
nervous  system,  works  as  a  single,  unitary  entity,  despite  its  com- 
plex differentiation  (see  also  p.  725). 

From  one  aspect  "states"  of  consciousness  is  an  inaccurate 
expression.  The  essential  features  of  consciousness  are  its  incessant 
change  and  its  intimate  relation  to  past  and  future  consciousness ; 
whereas  the  word  state  implies  a  period  of  rest  and  a  certain  isolation 
or  independence.  Save  for  this  difficulty,  it  would  be  possible  to 
regard  a  given  state  of  consciousness  as  the  cross-section  of  a  stream 
which  is  always  flowing.  The  simile  may  be  deemed  of  value,  in  so 
far  as  it  allows  us  to  represent  different  levels  of  conscious  states. 
At  any  moment,  there  is  always  part  which  is  in  the  focus,  or  full 
glare  of  consciousness,  and  part  of  which  we  are  dimly  conscious  or 
wholly  unconscious,  but  of  which  we  may  at  any  moment  become 
conscious — for  example,  the  ticking  of  a  clock  in  the  room  or  the 
pressure  of  a  pipe  between  the  teeth  while  these  lines  are  being 
written  or  read.  We  may  imagine  that  as  the  stream  of  conscious- 
ness flows  on,  different  portions  come  to  the  surface  at  different 
times  and  under  different  conditions,  while  others  fall  below,  often 
to  such  a  depth  that  they  pass  altogether  beyond  the  margin  of  con- 
sciousness. 

To  speak  of  a  "  stream  of  consciousness  "  is  in  one  sense  correct ; 
but  at  any  moment  there  are  probably  innumerable  streams,  which, 
under  normal  circumstances,  play  the  part  of  a  single  or  unitary 
stream,  owing  to  that  integrative  activity  which  we  term  the  Ego. 
These  various  streams  at  any  moment  form  a  pattern,  but  that 
pattern  is  ceaselessly  changing,  as  the  streams  run  hither  and  thither. 

On  the  physiological  side,  we  see  the  analogue  of  these  streams 
in  the  streams  of  nervous  impulses  which  are  perpetually  coursing 
through  the  brain.  The  pattern  of  these  streams  is  likewise  always 
changing.  And  we  may  suppose  that  some  patterns  are  incom- 
patible with  the  simultaneous  occurrence  of  certain  other  patterns. 
In  this  way,  we  may  form  a  physiological  conception  of  the  basis  of 
inhibition;  the  pattern  which  inhibits  and  that  which  is  inhibited 
cannot  coexist.  This  incompatibility  has  doubtless  been  developed 


760          THE  PHYSIOLOGY  OF  CONSCIOUS  STATES       [CH.  LIT. 

in  evolutional   history   owing   to   the   necessity   of   adjustment  to 
environment. 

We  may  regard  the  physiological  correlate  of  consciousness  as 
a  state  of  resistance  to  the  onward  passage  of  the  nervous  impulse. 
When  the  resistance  is  high,  there  is  consciousness ;  when  it  is  low, 
there  is  none.  Thus  when  any  new  action  (such  as  skating  or 
bicycling)  is  being  learnt,  the  resistance  is,  as  we  should  expect, 
high.  But  the  more  often  that  act  is  repeated,  the  lower  becomes 
the  resistance,  until  ultimately  the  act  becomes  a  habit  and  is  per- 
formed in  the  complete  absence  of  consciousness  far  more  surely 
and  rapidly  than  in  the  earlier  stages  of  learning.  It  must  be  borne 
in  mind,  however,  that  this  conception  of  lowered  resistance  is  purely 
hypothetical.  We  have  no  actual  evidence  as  to  which  part  of  the 
neuron  it  is  that  offers  resistance,  although  we  may  conjecture  that 
the  resistance  occurs  at  the  synapses,  when  the  dendritic  processes 
of  one  neuron  meet  those  of  another. 

The  hypothesis  is  at  all  events  valuable  in  so  far  as  it  contradicts 
an  old  and  erroneous  conception  that,  as  an  action  becomes  habitual 
and  no  longer  accompanied  by  consciousness,  the  nervous  impulses 
quit  the  higher  parts  of  the  brain  and  confine  themselves  to  the  sub- 
cortical  and  spinal  regions.  There  can  be  no  doubt  that  nervous 
impulses  pursue  the  same  course  in  the  brain,  whether  at  one  moment 
consciousness  be  present,  or  at  another  absent. 

In  the  spinal  cord,  on  the  other  hand,  there  is  no  evidence  of  the 
presence  of  consciousness.  The  acts  which  are  executed  by  the 
isolated  cord  are  reflex.  In  so  far  as  they  are  unaccompanied  by 
consciousness,  they  are  comparable  to  habits  acquired  by  training  in 
the  higher  parts  of  the  nervous  system. 

Within  certain  limits,  reflex  actions  can  be  predicted.  If  we 
apply  a  known  stimulus  to  the  afferent  portion  of  a  reflex  system, 
we  can  with  fair  confidence  predict  the  result  of  the  stimulus  on  the 
efferent  portions  connected  therewith.  When,  on  the  other  hand,  the 
stimulus  involves  the  manifestation  of  consciousness,  prediction  is 
almost  impossible ;  there  is  so  little  fixity,  the  nervous  connections 
are  so  complex,  and  the  nervous  impulse  may  wander  in  such  a 
variety  of  directions,  that  one  cannot  forecast  with  certainty 
how  an  individual  will  behave  under  the  influence  of  external 
circumstances. 

It  is  common  to  speak  of  the  most  primitive  cognitive  experience 
as  sensation.  On  the  physiological  side,  sensation  involves  (1)  an 
end-organ  in  a  sensory  epithelium,  adapted  to  receive  the  stimulus ; 
(2)  a  sensory  nerve  path  transmitting  the  nerve  impulse,  which 
ultimately  reaches  (3)  a  sensory  centre  in  the  cortex  of  the  brain. 
But  it  is  very  doubtful  whether  the  sensory  cortical  areas  should  be 
regarded  as  the  "  seats "  of  sensation.  It  is  quite  conceivable  that 


CH.  LII.]  SENSATIONS   AND   REFLEXES  761 

they  are  merely  areas  through  which  the  nervous  impulses  must  pass 
in  order  that  the  corresponding  sensations  may  be  developed. 

In  any  case,  we  must  recognise  that  from  infancy  onwards  we 
never  have  a,  pure  sensation,  that  is  to  say,  an  experience  devoid  of 
meaning  and  totally  dissociated  from  past  experiences — an  experience 
only  dependent  on  end-organ,  nerve-fibre  and  sensory  centre.  Our 
experiences  come  to  us  for  the  purpose  of  adjusting  ourselves  to  the 
outer  world  ;  consequently  they  possess  such  meaning  as  is  necessary 
for  that  end.  It  is  true  that  in  infancy  our  states  of  consciousness 
are  vague ;  but  they  are  always  related  to  previous  experiences  and 
are  motives  for  action.  Thenceforth  they  gradually  become  more 
definite.  The  various  elements  which  they  contain  become  differen- 
tiated, recognised,  and  separated.  What  was  at  first  homogeneous  is 
later  found  to  consist  of  heterogeneous  parts.  . 

Consequently  it  is  incorrect  to  say,  as  is  so  often  said,  that  with 
growing  experience  sensations  are  grouped  together  so  as  to  give 
rise  to  the  perception  of  objects.  It  is  true  that  from  our  adult 
perception  of  an  object,  e.g.  of  an  orange,  certain  sensations  of  colour, 
taste,  smell,  etc.,  may  be  analysed  and  separated.  But  a  moment's 
reflection  will  convince  us  that  our  perception  of  the  orange  has 
never  arisen  by  the  converse  synthesis  or  building  together  of  such 
sensations.  From  infancy  onwards  the  world  appears  to  us  (however 
vaguely)  as  composed  of  objects.  The  sensations  of  which  we  have 
presently  to  treat  are  the  artificial  products  of  the  analytical  activity 
of  the  Ego. 

Eecognising  that  sensations  are  not  truly  immediate  experiences, 
but  are  very  abstract  in  origin,  we  may  proceed  to  consider  the 
various  characters  with  which  they  may  be  invested.  Sensations 
may  differ  from  one  another  in  modality  or  in  quality.  Mod  ally 
different  sensations  are  derived  from  different  senses,  qualitatively 
different  sensations  from  the  same  sense.  Blue  and  green  are 
qualitatively  different  sensations ;  it  is  possible  to  pass  by  gradual 
transition  from  one  to  the  other.  Heat  and  noise  are  modally 
different ;  such  gradual  transition  is  impossible. 

Now  every  peripheral  end-organ  is  specially  destined  to  respond 
to  a  certain  form  of  stimulus.  The  end-organs  of  the  ear  respond  to 
sound  waves :  those  of  the  eye  to  light  waves ;  those  of  the  skin  to 
heat,  cold,  touch,  and  pain.  That  stimulus  to  which  the  end-organ 
is  thus  fitted  to  respond,  is  called  its  adequate  or  homologous  stimulus. 
But  an  end -organ  will  often  respond  to  other,  inadequate,  stimuli. 
For  example,  when  the  eyeball  is  struck,  sparks  are  seen ;  when  a 
"cold  spot"  on  the  skin  is  stimulated  by  a  hot  point,  a  cold 
sensation  results ;  when  an  electric  current  is  applied  to  the  papillae 
of  the  tongue,  sensations  of  taste  arise. 

Hence  it  has  been   argued   that   the   modality   of   a   sensation 


762          THE  PHYSIOLOGY  OF  CONSCIOUS  STATES       [CH.  LII. 

depends  not  upon  the  nature  of  the  stimulus,  but  upon  the  nature 
of  the  sensory  apparatus  on  which  the  stimulus  acts.  Johannes 
Miiller  expressed  this  conception  in  what  is  known  as  the  law  of 
specific  nervous  energy.  He  supposed  that  every  sensory  apparatus 
had  its  own  "  specific  energy,"  and  that  that  energy  was  evoked  by 
any  stimulus  so  long  as  the  stimulus  was  at  all  effective.  We  have, 
however,  no  physiological  evidence  that  the  nerve  impulses  passing, 
say,  along  the  optic  fibres,  are  different  in  "  energy,"  or  in  any  other 
character,  from  those  which  are  transmitted,  say,  by  the  auditory 
fibres.  Indeed,  the  experiments  of  Langley  and  others  on  nerve- 
crossing  (p.  161)  would  seem  to  indicate  that  the  nervous  impulse  is 
an  identical  process  in  all  nerves.  It  may  be  that  the  "specific 
energy "  of  sensations  resides  in  the  various  sensory  centres  of  the 
brain.  But  if  that  be  so,  it  is  important  to  realise  how  dependent 
that  "energy"  is  for  its  development  on  the  corresponding  end- 
organs.  A  person  whose  visual  or  auditory  end-organs  have  been 
f unctionless  from  birth,  can  never  know  what  it  is  to  see  or  hear ; 
he  can  never  think  or  dream  in  terms  of  visual  or  auditory  imagery. 

Whether  qualitatively  different  sensations  involve  separate  end- 
organs,  or  whether  they  are  the  outcome  of  different  kinds  of 
activity  in  one  and  the  same  end-organ,  is  at  present  far  from  certain. 
Probably  there  are  a  few  "  primary  sensations  "  for  each  sense  organ, 
and  the  many  different  qualities  of  sensation  obtainable  are  due  to 
various  combinations  of  such  elements. 

We  know,  generally  speaking,  that  sensations  differ  in  quality 
according  to  the  rate  of  vibration  of  the  stimulus.  Sound  waves  of 
rapid  and  slow  vibration  give  rise  to  sensations  of  high  and  low 
pitch  respectively.  Light  waves  of  rapid  and  slow  vibration 
give  rise  to  sensations  of  blue  and  red  respectively.  Differences  in 
intramolecular  vibration  probably  give  rise  to  qualitative  differences 
in  olfactory,  gustatory,  and  thermal  sensations. 

The  strength  of  the  stimulus  (e.g.  the  amplitude  of  vibration) 
determines  a  third  character  in  which  sensations  may  differ  from 
one  another,  namely,  in  intensity  (for  instance,  the  loudness  of  a 
sound,  or  the  brightness  of  a  light). 

Yet  another  character  of  many  sensations  is  extensity,  or  "  spread- 
outness."  Smell  and  taste  and  some  other  sensations  seem  to  be 
devoid  of  extensity.  It  is  best  developed  in  visual  and  cutaneous 
sensations,  and  these  possess  yet  another  characteristic,  local  signa- 
ture. Every  point  stimulated  on  the  retina  or  skin  has  its  local 
sign,  in  virtue  of  which  we  are  able  to  localise  the  stimulus  at  that 
point  and  to  distinguish  the  sensation  from  those  produced  by  the 
stimulation  of  neighbouring  points.  On  the  basis  of  extensity  and 
local  signature  is  built  up  our  perception  of  extension,  form,  and 
spatial  relations  generally. 


en.  LIL]  SPECIFIC  NERVOUS  ENERGY  763 

The  remaining  characters  ascribable  to  sensation  are  protensity — 
on  which  our  perception  of  duration  is  based — and  affective  tone, 
which  give  us  our  experience  of  pleasure,  indifference,  or  displeasure. 
But  these  we  will  not  discuss ;  they  are  more  suitably  studied  in 
works  on  psychology. 

It  is  of  interest  to  note  how  intimately  the  various  characters  of 
sensation  are  bound  up  with  one  another.  If  we  attempt  experi- 
mentally to  change  one  character,  it  is  difficult  to  avoid  simultane- 
ously changing  another.  For  example,  when  we  increase  the 
extensity  of  a  warm  sensation  by  putting  more  of  our  arm  into  hot 
water,  we  at  once  increase  the  intensity  of  the  sensation.  If  we 
increase  the  area  of  a  very  distant  colour  stimulus,  we  alter  its  hue. 
The  hue  of  a  colour  is  also  apparently  altered  by  increasing  the 
intensity  of  the  stimulus.  To  many  people  the  pitch  of  a  sound 
appears  altered  by  increasing  its  loudness. 

It  is  likewise  important  to  remember  that  the  characters  of  a 
sensation  depend  not  only  on  the  strength,  vibration-rate,  duration, 
etc.,  of  the  stimulus,  but  also  upon  the  condition  of  the  sensory 
apparatus  which  is  stimulated  and  upon  the  temporary  condition  of 
neighbouring  sensory  areas;  nay,  the  characters  of  a  sensation 
depend  upon  the  state  of  the  nervous  system  generally,  that  is  to 
say,  upon  the  total  mental  state  at  the  moment  of  application  of  the 
stimulus. 

The  strength  of  a  stimulus  must  not  fall  below  a  certain 
minimum  in  order  that  a  sensation  may  result.  Too  light  a  touch, 
too  faint  a  sound,  will  produce  no  effect  on  consciousness.  That 
strength  of  stimulus  which  just  suffices  to  evoke  a  sensation  is  called 
the  liminal  (from  limen,  a  threshold)  *  value  of  the  stimulus,  or  its 
absolute  threshold. 

Similarly,  the  difference  between  two  stimuli  must  not  fall  below 
a  certain  minimum  in  order  that  that  difference  may  be  appreciated. 
If  two  musical  tones  are  of  too  nearly  identical  pitch,  if  two  colours 
are  of  too  nearly  identical  hue,  the  difference  may  be  imperceptible. 
There  is,  hence,  a  liminal  value  for  a  stimulus  difference.  This  is 
known  as  the  differential  threshold  of  the  stimulus. 

Weber's  law  states  that  the  just  appreciable  difference  between 
two  stimuli  depends  on  the  ratio  of  that  difference  to  their  magni- 
tudes, and  not  on  the  absolute  difference  between  their  magnitudes. 
Fechner,  after  bringing  forward  further  evidence  in  favour  of  the 
law,  endeavoured  to  deduce  from  it  the  conclusion  that  the  strength 
of  a  sensation  is  proportional  to  the  logarithm  of  its  stimulus ;  in 
other  words,  that  the  stimulus  must  increase  in  geometrical  pro- 
portion for  the  sensation  to  increase  in  arithmetical  proportion. 

*  Strictly  speaking,  the  liminal  value  is  that  strength  of  stimulus  which  in  a 
series  of  trials  as  often  just  fails  as  it  just  succeeds  in  evoking  a  sensation. 


764  THE  PHYSIOLOGY  OF  CONSCIOUS  STATES       [CH.  LII. 

Fechner's  interpretation  of  Weber's  law  is,  however,  open  to  serious 
criticism,  into  which  we  cannot  enter  here. 

Weber's  law  is  but  an  expression  of  everyday  experience.  A 
rushlight  will  brighten  a  dark  cellar,  but  its  presence  is  unfelt  in 
sunshine.  So,  too,  if  a  room  be  lighted  by  100  candles,  and  if  one 
candle  more  be  brought  in,  the  increased  illumination  produced  by 
the  extra  candle  would  be  just  perceptible  to  the  eye.  But  if  a 
room  were  lighted  by  1000  candles,  no  appreciable  difference  would 
result  from  the  introduction  of  an  extra  candle.  Ten  candles  would 
have  to  be  introduced,  in  order  to  effect  a  just  noticeable  difference. 
In  each  case  a  difference  of  one-hundredth  of  the  original  strength 
of  stimulus  is  needful  to  cause  a  just  appreciable  difference  in  the 
sensation;  and  this  is  in  accordance  with  Weber's  law. 

For  light,  the  fraction  is  about  y^ ;  for  noise,  it  is  about  J ;  for 
cutaneous  pressure,  it  varies  between  ^  and  ^ ;  for  weight,  between 
TV  and  ^V,  according  to  the  part  of  the  body  which  is  under 
investigation. 

A  sensation  requires  an  appreciable  time  for  its  development. 
Part  of  this  time  is  spent  at  the  end-organ  on  which  the  stimulus 
acts,  part  in  conveying  the  nervous  impulse  along  the  sensory  nerve 
to  the  brain,  and  part  within  the  brain  itself.  This  latent  period 
varies  in  length  according  to  the  sensation ;  e.g.,  it  is  longer  for  sight 
than  for  sound,  and  longer  for  pain  than  for  touch. 

A  sensation  outlasts  its  stimulus.  Indeed,  a  single  stimulus 
may  produce  a  whole  train  of  after-sensations.  These  are  specially 
noticeable  in  the  case  of  visual  sensations,  which  we  shall  be 
considering  later. 

When  the  sensation  and  its  after-sensations  have  passed  away, 
the  original  experience  may  still  be  revived,  either  spontaneously  or 
by  an  effort  of  volition.  This  revival  involves  what  is  called  the 
memory  image.  When,  in  this  way,  a  tune  "  comes  into  the  head," 
we  recognise  that  it  is  only  a  reproduction,  or  a  representation,  of 
what  we  have  previously  heard. 

Occasionally,  however,  the  revived  image  has  all  the  vividness 
and  distinctness  of  objective  experience,  and  we  believe  that  it  is 
"real."  In  other  words,  we  have  a  hallucination.  Hallucinations 
occur  normally  in  all  people ;  but  they  are,  of  course,  particularly 
common  in  sleep  and  in  conditions  of  insanity  or  delirium. 

It  is  still  disputed  whether  the  difference  between  original  and 
revived  experiences  corresponds  to  an  excitement  of  distinct  regions 
of  the  brain.  Some  physiologists  have  gone  so  far  as  to  speak  of 
"  memory  centres  "  as  existing  apart  from  the  sensory  centres  which 
are  supposed  originally  to  have  excited  them,  and  they  have 
considered  that  the  recall  of  a  scene  or  of  a  tune  is  due  to  the  re- 
excitation  of  the  appropriate  memory  centres,  while  the  correspond- 


CH.  LII.]  WEBER'S  LAW  765 

ing  sensory  centres  are  quiescent.  The  balance  of  evidence,  however, 
is  very  strongly  against  this  view.  It  is  better  to  suppose  that  the 
physiological  processes  underlying  a  sensation  and  its  revived 
memory  image  are  broadly  the  same.  There  is  unquestionably 
some  physiological  difference  corresponding  to  the  difference  between 
sensory  experiences  and  hallucinations  on  the  one  hand,  and  revived 
experiences  on  the  other.  But  at  present  it  is  impossible  to  say  in 
what  that  difference  consists. 

When,  as  occurs  under  certain  conditions,  an  object  is  adjudged 
different  from  what  general  experience  teaches  us  to  be  its  "  real " 
character,  we  have  an  illusion.  Thus  a  line  or  figure  may  appear  to 
be  longer  or  shorter  than  it  really  is,  or  to  take  a  direction  different 
from  its  real  direction.  Or  a  weight  may  appear  heavier  than 
another  which  is  really  equal  to  it.  Illusions  are  due  partly  to 
peripheral,  partly  to  central  factors.  Their  investigation  falls  within 
the  province  of  experimental  psychology. 


CHAPTEE   LTII 


CUTANEOUS    SENSATIONS 

THE  tactile  end-organs  are  of  numerous  kinds,  but  the  following  are 
the  principal  ones  : — 

Pacinian  Corpuscles. — These  are  named  after  their  discoverer 
Pacini.  They  are  little  oval  bodies,  situated  on  some  of  the  cerebro- 
spinal  and  sympathetic  nerves,  especially  the  cutaneous  nerves  of 
the  hands  and  feet,  where  they  lie  deeply 
placed  in  the  true  skin.  They  also  occur 
on  the  nerves  of  the  mesentery  of  some 
animals  such  as  the  cat.  They  have  been 
observed  also  in  the  pancreas,  lymphatic 
glands,  and  thyroid  glands,  as  well  as  in  the 
penis.  They  are  about  TV  inch  long.  Each 
corpuscle  is  attached  by  a  narrow  pedicle  to 
the  nerve  on  which  it  is  situated,  and  is 
formed  of  several  concentric  sheaths  of  con- 
nective tissue,  each  layer  being  lined  by 
endothelium  (figs.  466,  467);  through  its 
pedicle  passes  a  single  nerve-fibre,  which 
loses  its  medullary  sheath  and  enters  a 
central  core,  at  or  near  the  distal  end  of 
which  it  terminates  in  an  arborisation.  Some 
of  these  layers  are  continuous  with  those 
of  the  perineurium,  but  some  are  super- 
added.  In  some  cases  two  nerve-fibres 
have  been  seen  entering  one  Pacinian  body, 
and  in  others  a  nerve-fibre  after  passing 
through  it  has  been  observed  to  terminate 
in  a  second. 

The  corpuscles  of  Herlbst  (fig.  468)  are 

closely  allied  to  Pacinian  corpuscles,  except  that  they  are  smaller 
and  longer,  with  a  row  of  nuclei  around  the  central  termination 
of  the  nerve  in  the  core.  They  have  been  found  chiefly  in  the 
tongues  and  bills  of  ducks. 

766 


FJG.  465.— Extremities  of  a  nerve 
of  the  finger  with  Paciuian  cor- 
puscles attached,  about  the 
natural  size.  (Adapted  from 
Henle  and  Kolliker.) 


CH.  LIU.] 


TACTILE   END  ORGANS 


767 


End-bulbs  are  found  in  the  conjunctiva  (where  in  man  they  are 
ppheroidal,  but  in  most  animals  oblong),  in  the  glans  penis  and 

clitoris,  in  the  skin  of  the  lips,  in 
the  epineurium  of  nerve-trunks, 
and  in  tendon ;  each  is  about  -^^ 
inch  in  diameter,  oval  or  spheroidal, 


PIG.  467.— Summit  of  a  Pacinian  cor- 
puscle of  the  human  finger  showing 
the  endothelial  membranes  lining  the 
capsules,  x  220.  (Klein  and  Noble 
Smith.) 

and  is  composed  of  a  medullated 
nerve  -  fibre,  which  terminates 
among  cells  of  various  shapes.  Its 
capsule  contains  a  transparent  or 
striated  core,  in  the  centre  of 
which  the  axis-cylinder  terminates 
(fig.  469). 

Touch-corpuscles  (Meissner's 
corpuscles)  (figs.  470,  472),  are 
found  in  the  papillae  of  the  skin 
of  the  fingers  and  toes.  They  are 
oblong,  about  ^^  inch  long,  and  -^y  inch  broad,  and  composed 
of  connective  tissue,  surrounded  by  elastic  fibres  and  a  capsule  of 
nucleated  cells.  They  do  not  occur  in  all  the  papillae  of  the 
parts  where  they  are  found,  and,  as  a  rule,  in  the  papillae  in  which 
they  are  present  there  are  no  blood-vessels. 


FIG.  466. — Pacinian  corpuscle  of  the  cat's  mesen- 
tery. The  stalk  consists  of  a  nerve-fibre  (N) 
with  its  thick  outer  sheath.  The  peripheral 
capsules  of  the  Pacinian  corpuscle  are  con- 
tinuous with  the  outer  sheath  of  the  stalk. 
The  intermediary  part  becomes  much  nar- 
rower near  the  entrance  of  the  axis-cylinder 
into  the  clear  central  core.  A  hook-shaped 
termination  (T)  is  seen  in  the  upper  part.  A 
blood-vessel  (V)  enters  the  Paciuian  corpuscle, 
and  approaches  the  end  ;  it  possesses  a  sheath 
which  is  the  continuation  of  the  peripheral 
capsules  of  the  Pacinian  corpuscle,  x  100. 
(Klein  and  Noble  Smith.) 


768 


CUTANEOUS   SENSATIONS 


[CH.  LIII. 


The  peculiar  way  in  which  the  medullated  nerve  winds  round 
and  round  the  corpuscle  before  it  enters  it  is  shown  in  fig.  472.     It 


FIG.  468. — A  corpuscle  of  Herbst,  from 
the  tongue  of  a  duck,  a,  Medullated 
nerve  cut  away.  (Klein.) 


FIG.  469. — End-bulb  of  Krause.  o,  Me- 
dullated nerve-fibre;  b,  capsule  of 
corpuscle. 


loses  its  sheath  before  it  enters  into  the  interior,  and  then  its  axis- 
cylinder  branches,  and  the  branches  after  either  a  straight  or  con- 
voluted course  terminate  within  the  corpuscle. 


FIG.  470.— Papillse  from  the  skin  of  the  hand,  freed  from  the  cuticle  and  exhibiting  Meissner's  corpuscles. 

A.  Simple  papilla  with  four  nerve-fibres ;  a,  tactile  corpuscle ;  b,  nerves  with  winding  fibres  c  and  e. 

B.  Papilla  treated  with  acetic  acid ;  a,  cortical  layer  with   cells  and   fine  elastic   filaments ;  b, 
tactile  corpuscle  with  transverse  nuclei ;  c,  entering  nerve ;  d  and  e,  nerve-fibres  winding  round 
the  corpuscle,     x  350.    (Kolliker.) 

The  corpuscles  of  Grandry  (fig.  471)  form  another  variety,  and 
have  been  noticed  in  the  beaks  and  tongues  of  birds.  They  consist 
of  oval  or  spherical  cells,  two  or  more  of  which  compressed  vertically 


CH.  LIIL] 


TACTILE   END-OKGANS 


769 


are  contained  within  a  delicate  nucleated  sheath.  The  nerve  enters 
on  one  side,  and,  laying  aside  its  medullary  sheath,  terminates 
between  the  cells  in  flattened  expansions. 


FIG.  471.— A  corpuscle  of 
Grandry,.  from  the 
tongue  of  a  duck. 


FIG.  472.— A  touch-corpuscle  from  the  skin  of  the 
human  hand,  stained  with  gold  chloride. 


Sensory  nerve  -  endings  in  muscle.  —  Nerve  terminations, 
sensory  in  function,  are  found  in  tendon.  Some  of  these  are  end- 
bulbs,  and  others  appear  very  much  like  end-plates,  as  represented  in 
figs.  471  and  472.  The  neuro-muscular  spindles,  one  of  which  is 


FIG.  473.— Termination  of  inedullated 
nerve-fibres  in  tendon  near  the  mus- 
cular insertion.  (Golgi.) 


FIG.  474.— One  of  the  reticulated  end-plates 
of  fig.  473,  more  highly  magnified,  a, 
MeduUated  nerve-fibre;  b,  reticulated 
end-plate.  (Golgi.) 


shown  in  the  accompanying  drawing  (fig.  475),  are  principally  found 
in  muscles  in  the  neighbourhood  of  tendons  and  aponeuroses. 

The  principal  grounds  for  believing  the  neuro-muscular  spindles 
to  be  sensory  are,  first,  that  the  nerve-fibres  that  supply  them  do 
not  degenerate  when  the  anterior  roots  of  the  spinal  nerves  are  cut, 
and  secondly,  that  they  do  degenerate  when  the  posterior  roots  are 
divided  (Sherrington).  They  also  undergo  degenerative  changes  in 

3  c 


770 


CUTANEOUS   SENSATIONS 


[CH.  Mil. 


locomotor  ataxy,  which  is  a  disease  of  the  sensory  nerve-units,  and 
remain  healthy  in  infantile  paralysis,  which  is  a  disease  of  the 
motor  cells  of  the  anterior  horn  of  the  cord  (Batten). 


m.h.b. 


PIG.  475.— Neuromuscular  spindle,    c.,  Capsule;  n.tr.,  nerve  trunk;  m.n.b.,  motor  nerve  bundle; 
pl.e.,  plate-ending;  pr.e.,  primary  nerve-ending;  s.e.,  secondary  ending.    (After  Ruflini.) 


In    addition    to    the 


special  end-organs,  sensory  fibres  may 
terminate  in  plexuses  of  fibrils,  as  in 
the  subepithelial  and  the  intra-epithelial 
plexus  of  the  cornea  (fig.  476)  and 
around  the  hair  follicles  in  the  skin 
generally  (see  fig.  392,  p.  607).  In  some 
cases  the  nerve-fibrils  within  a  stratified 
epithelium  end  in  crescentic  expansions 
(tactile  discs')  which  are  applied  to  the 
deeper  epithelium  cells.  These  are  well 
seen  in  the  skin  of  the  pig's  snout. 

Localisation  of  Tactile  Sensations. 

The  localisation  of  a  tactile  sensation 
is  of  two  kinds,  absolute  and  relative. 
We  can  localise  a  touch  on  the  arm 
absolutely  by  indicating  the  exact  spot 
which  has  been  touched,  or  we  may 
localise  it  relatively  to  another  spot  on 
the  arm  which  is  simultaneously  or  suc- 
cessively touched.  Generally  speaking, 
the  delicacy  of  these  two  kinds  of  locali- 
sation is  similarly  variable  in  different 
parts  of  the  body. 

The   "local    signature"   (p.    762)    of 
cutaneous  sensations  may  be  easily  inves- 
tigated by  touching  the  skin,  while  the 
eyes  are  closed,  with  the  points  of  a  pair 
of  compasses,  and  ascertaining  how  close  the  points  may  be  brought 


FIG.  476.— Vertical  section  of  rabbit's 
cornea,  stained  with  gold  chloride. 
The  nerves,  n,  terminate  in  a  plexus 
uuder  and  within  the  epithelial 
layer,  e. 


CH.  LIII.]  TACTILE   LOCALISATION  771 

to  each  other,  and   still   be   felt  as  two  points.     (Weber.)     A  few 
results  are  as  follow  : — 

Tip  of  tongue 7jVinch  1  mm. 

Palmar  surface  of  third  phalanx  of  forefinger        .     TV  2 


Palmar  surface  of  second  phalanges  of  fingers 

Palm  of  hand 

Dorsal  surface  of  first  phalanges  of  fingers  . 
Back  of  hand 


Upper  and  lower  parts  of  forearm         .         .  1^ 

Middle  of  thigh  and  back 2| 


4 

10 
14 
25 
37 
62 


In  the  case  of  the  limbs,  it  is  found  that  before  they  are  recognised 
as  two,  the  points  of  the  compasses  have  to  be  further  separated  when 
the  line  joining  them  is  in  the  long  axis  of  the  limb,  than  when  in 
the  transverse  direction. 

We  may  thus  assume  that  minute  areas  of  the  body  surface  have 
each  their  "  local  sign,"  i.e.,  the  sensation  arising  from  stimulation  of 
one  area  differs  in  some  obscure  quality  from  the  sensations  arising 
from  stimulation  of  neighbouring  areas,  thereby  acquiring  its  own 
spatial  colouring  which  enables  us  to  identify  the  area  when  stimulated. 
The  difference  of  local  sign  between  two  near  points  may  be  imper- 
ceptible in  one  region  of  the  body,  but  fully  recognisable  in  another. 
Again,  the  delicacy  of  the  sense  of  touch  may  be  very  much  increased 
by  practice.  A  familiar  illustration  occurs  in  the  case  of  the  blind, 
who,  by  constant  practice,  can  acquire  the  power  of  reading  raised 
letters,  the  forms  of  which  are  almost  if  not  quite  undistinguishable 
by  the  sense  of  touch  to  an  ordinary  person. 

The  different  delicacy  of  local  signature  possessed  by  different 
parts  may  give  rise  to  errors  of  judgment  in  estimating  the  distance 
between  two  points  where  the  skin  is  touched.  Thus,  if  the  blunted 
points  of  a  pair  of  compasses  (maintained  at  a  constant  distance 
apart)  are  slowly  drawn  over  the  skin  of  the  cheek  towards  the  lips, 
it  is  almost  impossible  to  resist  the  conclusion  that  the  distance 
between  the  points  is  gradually  increasing.  When  they  reach  the 
lips  they  seem  to  be  considerably  further  apart  than  on  the  cheek. 
Then,  too,  our  estimate  of  the  size  of  a  cavity  in  a  tooth  is  usually 
exaggerated  when  based  upon  sensations  derived  from  the  tongue 
alone.  Another  curious  illusion  is  the  following: — If  we  close 
the  eyes,  and  place  a  marble  between  the  crossed  fore  and  middle 
fingers,  we  seem  to  be  touching  two  marbles.  This  illusion  is  due 
to  an  error  of  judgment.  The  marble  is  touched  by  two  surfaces 
which,  under  ordinary  circumstances,  could  only  be  touched  by  two 
separate  marbles ;  hence,  regardless  of  the  fact  that  the  fingers  are 
crossed,  the  judgment  is  formed  that  the  two  sensations  are  due  to 
two  marbles. 


772  CUTANEOUS   SENSATIONS  [CH.  LIII. 

Varieties  of  Cutaneous  Sensations. 

The  surface  of  the  skin  is  a  mosaic  of  tiny  sensorial  areas ;  but 
these  areas  are  not  set  edge  to  edge  as  in  the  retina,  but  separated 
by  relatively  wide  interval  which  are  not  sensitive  to  stimuli  just 
above  liminal  intensity.  If  the  stimuli  are  made  nearly  minimal, 
the  individual  fields  are  reduced  to  small  spots.  Each  of  these  spots 
subserves  a  specific  sense,  touch,  cold,  heat  or  pain,  and  each 
doubtless  coincides  with  the  site  of  some  special  end-organ,  placed 
either  singly  or  in  clusters.  The  "touch  spots,"  "cold  spots," 
"heat  spots,"  and  "pain  spots"  are  intercommingled.  In  some 
districts  one  variety  predominates,  in  others  another.  "  Pain  spots  " 
are  the  most  and  "heat  spots"  the  least  numerous.  It  is  a 
matter  of  common  experience  that  the  sensitiveness  of  these  varieties 
of  cutaneous  sensation  differs  in  different  parts  of  the  body.  The 
tip  of  the  finger,  which  is  very  sensitive  to  the  true  tactile  sense 
(sense  of  pressure  or  contact),  is  not  nearly  so  sensitive  to  alterations 
of  temperature  as  the  forearm  or  cheek,  to  which  a  washerwoman 
generally  holds  her  iron  when  forming  a  judgment  of  its  temperature. 
Some  parts  of  the  skin  are  more  sensitive  to  pain  than  others,  and 
in  the  cornea  we  have  an  instance  of  a  surface  in  which  "  pain  spots  " 
alone  are  present. 

For  the  more  accurate  exploration  of  the  skin,  cesthesiometers  of 
various  kinds  have  been  invented.  The  sense  of  pressure  may  be 
estimated  by  the  ability  of  the  skin  to  distinguish  different  weights 
placed  upon  it;  there  must  be  no  lifting  of  the  weight,  or  the 
motorial  sense  is  brought  into  play.  The  fraction  which  by  Weber's 
law  represents  the  differential  threshold  (see  p.  763)  varies 
from  -gV  to  more  than  -^  in  different  parts  of  the  body.  It  does  not, 
however,  follow  that  the  acuteness  of  the  pressure  sense  varies 
exactly  as  the  ability  of  accurately  localising  sensations ;  for  instance, 
the  skin  of  the  forearm  is  as  sensitive  to  pressure  changes  as  that 
of  the  palm ;  and  the  tip  of  the  tongue,  which  is  the  most  discrimi- 
native region  of  the  body  for  locality,  is  not  so  for  pressure.  For 
pressure  stimuli  which  are  near  the  limen  or  threshold  of  sensa- 
tion, the  hair  sesthesiometer  is  much  used;  this  is  a  hair  suitably 
mounted  in  a  holder ;  the  hair  can  then  be  shifted  backwards  or  for- 
wards in  the  holder,  and  the  amount  of  pressure  it  exercises  can 
thus  be  varied.  It  is  used  for  the  exploration  of  "  touch  spots,"  and 
these  are  found  most  numerously  around  the  hair  follicles.  The 
touch  spots  are  more  numerous  in  some  parts  than  in  others,  but 
fifteen  for  each  square  centimetre  of  skin  is  a  rough  average.  To 
explore  "  pain  spots "  a  stout  hair  or  needle  is  used ;  in  the  latter 
case  the  needle  shifts  up  and  down  in  the  holder,  and  works 
against  a  spring  which  registers  the  amount  of  pressure  exerted  to 


CH.  MIL] 


VARIETIES   OF   CUTANEOUS   SENSATIONS 


773 


evoke  a  painful  sensation.  The  sensation  evoked  by  a  "  pain  spot "  is 
unaccompanied  by  "cold"  or  "heat,"  even  if  a  cold  or  hot 
needle  is  used.  For  the  exploration  of  "  heat  spots  "  a  small,  hollow, 
metallic  pencil  is  kept  warm  by  a  stream  of  warm  water;  this  is 
moved  over  the  surface ;  at  the  site  of  the  "  heat  spots "  the  pencil 
will  feel  peculiarly  warmer.  "  Cold  spots  "  can  be  similarly  mapped 
out  by  the  use  of  a  cold  pencil.  The  accompanying  figure  (fig.  477) 
indicates  the  distribution  of  cold  and  heat  spots  over  six  squares, 
each  of  1  sq.  cm.,  on  the  back  of  the  left  hand.  The  black  dots 


Fio.  477.— Heat  and  cold  spots.    (Somewhat  enlarged ;  after  Donaldson.) 

represent  cold  spots,  their  size  indicating  the  strength  of  the 
reaction.  The  open  circles  represent  heat  spots. 

All  these  facts  clearly  indicate  that  different  varieties  of  sensation 
are  the  result  of  the  stimulation  of  different  end-organs,  and  that  the 
impulses  are  conveyed  to  the  central  nervous  system  by  different 
groups  of  nerve-fibres;  they  moreover  form  the  clearest  piece  of 
evidence  we  have  that  pain  is  a  distinct  kind  of  sensation. 

The  question  is  more  difficult  to  answer,  which  particular  end- 
organ  is  concerned  with  each  variety  of  sensation.  There  is,  how- 
ever, little  doubt  that  the  nerve-fibrils  around  the  hair  follicles  of 
the  short  hairs  are  the  terminations  most  affected  by  changes  of 
pressure,  and  also  that  Meissner's  corpuscles  are  purely  tactual, 
taking  the  place  of  hairs  in  hairless  parts.  In  the  palmar  surface 
of  the  last  phalanx  of  the  index  finger,  there  are  21  Meissner's 
corpuscles  per  square  centimetre;  in  other  parts  of  the  palm  and 
sole  the  number  varies  from  2  to  8.  End-bulbs  are  believed  to 


774  CUTANEOUS   SENSATIONS  [CH.  LIII. 

be  the  organs  for  cold;  they  are  most  numerous  in  the  conjunctiva 
and  glans  penis,  where  "  cold  spots  "  are  almost  exclusively  present. 
The  end-organs  in  "heat  spots"  have  not  been  identified  with 
certainty,  but  they  are  probably  larger  organs,  and  placed  more 
deeply  in  the  skin. 

We  have  spoken  of  the  pressure  sense  as  the  true  tactile  sense ; 
but  Meissner  pointed  out  many  years  ago  that  the  hand  immersed  in 
a  fluid  such  as  mercury  at  body-temperature,  does  not  feel  the  contact 
of  the  fluid,  although  the  fluid  pressure  may  be  far  above  the  limen ; 
it  is,  however,  equal  in  all  directions ;  it  is  therefore  clear  that  the 
adequate  stimulus  for  touch  organs  consists  in  a  deformation  of  the 
skin  surface. 

As  compared  with  the  sensation  obtained  from  pain  spots,  touch 
is  quicker  both  in  development  and  subsidence.  Thus  vibrations  of 
strings  are  recognisable  as  such  by  the  finger,  even  at  a  frequency 
of  1500  vibrations  per  second.  A  revolving  wheel  with  toothed  edge 
does  not  give  a  sensation  of  smoothness  till  the  teeth  meet  the  skin 
at  the  rate  of  from  480  to  640  per  second. 

Head,  in  his  recent  study  of  nerve-regeneration,  cut  one  of  the 
nerves  in  his  own  arm,  and,  in  conjunction  with  Eivers,  noted 
accurately  the  date  and  other  particulars  of  return  of  function.  The 
first  sensations  return  about  the  eightieth  day  after  the  operation ; 
they  are  termed  by  him  protopathic.  Protopathic  sensibility  depends 
on  definite  specific  end-organs  distributed  over  the  skin  as  sensory 
"  spots,"  viz.,  heat,  cold,  and  pain  spots.  When  this  sensibility  is 
alone  present,  the  spaces  between  these  spots  are  insensitive  to 
cutaneous  stimuli ;  the  heat  spots  only  react  to  temperatures  above 
37°  C.,  the  cold  only  to  temperature  below  26°  C. ;  the  sensation 
radiates  widely,  and  is  often  wrongly  localised.  The  tactile  sensa- 
tions of  the  skin,  the  intermediate  temperature  sensations,  the  power 
to  localise  them  accurately,  the  sensibility  of  the  spaces  between  the 
spots,  and  a  more  refined  sensibility  to  pain,  return  much  later, 
and  this  epicritic  sensibility  was  not  perfect  until  many  months 
after  the  regeneration  started.  As  previously  stated  (p.  706),  it 
is  not  known  whether  protopathic  and  epicritic  impulses  are  sub- 
served by  the  same  or  by  different  nerve-fibres.  Quite  apart  from 
these  two  forms  of  cutaneous  sensation  is  the  deep  sensibility  of 
subjacent  structures,  and  the  fibres  subserving  this  run  mainly  with 
the  motor  nerves ;  this  form  of  sensation  is  not  destroyed  by  division 
of  all  the  nerves  to  the  skin  (see  also  p.  705). 

Adaptation  plays  a  part  as  important  in  cutaneous  as  in  other  sensations.  The 
same  room  feels  warm  to  a  man  who  enters  it  from  the  street,  and  cold  to  another  who 
has  been  in  a  conservatory.  Hering  calls  the  point  of  adaptation  to  temperature  ' '  the 
physiological  zero."  Thus  the  temperature  of  the  mouth  and  the  lips  may  actually 
differ  by  several  degrees,  yet  neither  of  them  will  feel  hot  or  cold  because  each  is  at 
the  physiological  zero  temperature.  Sensations  of  warmth  or  cold  arise  when  the 


CH.  L1II.]  PKOTOPATHIC   AND   EPICRITIC   SENSATIONS  775 

physiological  zero  is  altered :  they  persist  until  a  new  zero  is  formed,  i.e.  until  adapta- 
tion is  complete ;  according  to  Rivers  and  Head,  adaptation  to  temperature  is 
impossible  when  epicritic  sensibility  is  absent.  So,  too,  heavy  weights  feel  unduly 
heavy  after  light  weights,  and  vice  versa.  When  eyeglasses  or  false  teeth  are  first 
worn,  their  contact  is  well-nigh  unbearable;  yet  later,  through  adaptation,  the  dis- 
comfort vanishes. 

It  is  very  difficult  to  draw  any  hard-and-fast  line  between  the  cutaneous  sensa- 
tions we  have  just  described,  and  those  which  are  grouped  under  the  name  **  common 
or  general  sensibility  (coencesthesia)."  Sensations  which  are  difficult  to  describe  but 
which  are  perfectly  familiar,  such  as  those  accompanying  tickling,  shivering,  shudder- 
ing, and  the  like,  are  regarded  as  varieties  of  "common  sensation."  Pain  may  be 
looked  upon  as  an  excessive  form  of  "common  sensation,"  but  cutaneous  pain  is 
so  distinct  a  sensation  that  most  psychologists  agree  to  place  it  under  a  "  special" 
rather  than  a  "  common  "  heading.  The  term  "common  sensation  "  is  most  frequently 
employed  in  reference  to  sensations  from  the  interior  of  the  body. 

Drugs.—  Cocaine  applied  locally  depresses  all  forms  of  cutaneous  sensibility, 
but  especially  the  true  tactile  sense  ;  carbolic  acid  acts  similarly  but  less  strongly. 
Chloroform  produces  a  temporary  burning  sensation,  and  then  blunts  sensibility, 
especially  to  temperature  changes.  Menthol  produces  a  feeling  of  local  cold  because 
it  first  causes  hyperaesthesia  of  the  end-organs  for  cold  ;  this  is  followed  by  a  depres- 
sion of  the  activity  of  these  organs,  together  with  that  subserving  other  forms  of 
cutaneous  sensation. 


CHAPTEE  LIV 

MOTORIAL  AND  VISCERAL  SENSATIONS 

WE  shall  in  the  present  chapter  deal  with  the  motorial  or  muscular 
sense,  and  with  sensations  from  the  viscera. 

The  Motorial  or  Kinaesthetic  Sense. 

By  this  sense  we  become  aware  that  movement  is  taking  place  in 
some  part  of  the  body.  We  are  especially  conscious  of  willed  muscular 
action,  and  the  sense  has  thus  been  confused  and  identified  with  the 
rt  feeling  of  innervation,"  or  "  sense  of  effort,"  which  accompanies  voli- 
tional movements.  By  some  this  feeling  has  been  attributed  to  a  direct 
discharge  from  the  motor  to  the  sensory  cells  of  the  cerebral  cortex 
occurring  at  the  very  birth  of  the  efferent  impulse.  No  doubt  part  of 
the  effect  involved  in  movement  is  of  central  origin,  and  this  part  is 
the  effect  inherent  in  all  conative  (p.  758)  processes,  and  characterises 
all  forms  of  mental  activity,  for  instance,  reasoning  or  imagination ; 
but  its  physiological  basis  is  quite  unknown.  Most,  however,  of  the 
sense  of  effort  is  unquestionably  due  to  afferent  impulses  peripherally 
generated  by  the  accompanying  respiratory  and  other  strains. 

It  is  in  the  estimation  of  weights  that  the  value  of  these  peripheral 
sensations  can  be  most  clearly  seen.  When  a  weight  is  first  handled, 
the  amount  of  force  necessary  to  lift  it  is  estimated  in  the  light  of 
past  experience.  As  it  is  being  lifted,  sensations  from  the  moving 
limb  guide  the  expenditure  of  force :  a  weight  which  flies  up  too  fast 
or  does  not  move  at  once,  calls  for  less  or  more  muscular  force. 
Similarly,  the  motorial  sense  is  invoked  when  we  estimate  the  extent 
to  which  we  have  moved  our  limbs,  or  to  which  they  have  been 
passively  moved  by  others. 

These  guiding  sensations  are  not  merely  of  cutaneous  origin. 
Persons  whose  skin  has  been  rendered  insensitive  by  cocaine,  or  by 
certain  diseases,  yet  retain  the  power  of  estimating  weights  and  the 
extent  of  their  movements.  In  locomotor  ataxy  the  motorial  sense 
may  be  destroyed  while  the  skin  retains  its  usual  sensitiveness  to 
touch.  On  the  other  hand,  we  must  remember  that  it  is  not  at  all 
certain  that  the  muscles  are  solely  or  even  predominantly  the  seat  of 
these  peripheral  sensations ;  the  term  "  motorial "  or  "  kinsesthetic  " 
is  therefore  preferable  to  that  of  "  muscular  "  sense,  by  which  name 

776 


CH.  LIV.]  VISCERAL  SENSATIONS  777 

it  is  still  often  called.  It  is  true  that  sensory  end-organs  and 
nerve-fibres  occur  in  muscles  and  tendons,  which  presumably  transmit 
impulses  upon  change  of  muscular  form  or  of  tendinous  strain.  But 
we  have  experimental  evidence  that  the  pressure  and  movement  of  joint- 
surfaces  are  most  important  factors  in  the  development  of  kinsesthetic 
sensations.  The  "  motorial  sense  "  is  thus  of  very  complex  origin. 

Visceral  Sensations. 

Epicritic  sensibility  is  a  special  characteristic  of  the  cutaneous 
area.  Protopathic  sensibility  is  found  in  other  parts  also,  but  in 
most  internal  structures  of  the  body  it  is  limited  to  pain.  The 
oesophagus  and  anal  canal  alone  seem  to  be  endowed  with  the  tempera- 
ture sense ;  the  feelings  of  warmth  and  cold  on  swallowing  liquids  of 
different  temperatures  are  entirely  referable  to  the  upper  portion  of 
the  alimentary  canal.  Hertz's  recent  experiments  place  this  beyond 
question ;  immediately  the  food  has  passed  into  the  stomach  we  are 
unaware  of  its  temperature  except  by  the  warming  or  cooling  of  the 
neighbouring  portion  of  the  gullet,  or  the  skin  overlying  the  viscera. 

Pain  is  the  most  widely  distributed  sense  in  the  body,  but  in 
internal  organs  is  not  localised  accurately,  and  it  is  here  that  the 
"referred  pains"  in  corresponding  skin  areas  (see  p.  205)  are  useful 
for  diagnostic  purposes.  Pain,  however,  is  not  produced  in  the 
viscera  by  handling  or  even  by  cutting  or  burning :  it  appears  to  be 
associated  with  excessive  action,  stretching,  and  with  inflammatory 
conditions  which  involve  the  sensitive  parietal  layer  of  the  peri- 
toneum. Inflammation  of  the  serous  membranes  is  an  exceedingly 
painful  condition — for  instance,  in  pleurisy  and  peritonitis — but  this 
condition,  per  se,  does  not  apparently  cause  any  referred  pain  or 
tenderness  in  cutaneous  areas.  In  connection  with  the  question  of 
referred  pain,  we  must  mention  the  pathological  condition  known 
as  allochiria.  When  the  skin  sensations  in  any  given  area  are 
depressed,  stimulation  of  that  area  may  give  rise  to  sensations  which 
are  referred  to  the  corresponding  area  on  the  other  side  of  the  body ; 
it  appears  to  be  a  general  rule,  as  Head  first  pointed  out,  that  the 
mind  projects  sensations  arising  from  an  area  of  low  sensibility  to 
that  area  of  higher  sensibility  which  is  related  to  it  most  closely  by 
connections  within  the  central  nervous  system,  and  this  underlies  the 
causation  of  referred  visceral  pains. 

There  are,  however,  special  kinds  of  sensation  arising  from 
internal  viscera  which  have  no  counterpart  in  the  sensations  of  the 
cutaneous  surface.  Of  these,  hunger  and  thirst  are  the  most  familiar. 

Hunger  when  slight  is  termed  appetite,  and  there  is  some  differ- 
ence of  opinion  whether  the  two  are  separate  sensations,  or  only 
differ  in  degree.  Appetite  is  referred  to  the  stomach,  and  is  a 
normal  sensation,  which  arises  at  an  interval  after  a  meal,  and  as  is 


778  MOTORIAL  AND   VISCERAL  SENSATIONS  [CH.  LIV. 

well  known  it  is  intensified  by  muscular  exertion,  especially  if  the 
air  is  cool.  It  has  been  suggested  that  the  oxidation  processes  which 
occur  in  the  muscles  produce  some  substance  or  substances  which 
excite  the  sensory  nerve-terminals  in  the  stomach.  In  diabetes, 
where  oxidation  runs  an  unusual  course,  carbohydrates  escaping 
oxidation  to  a  large  extent,  intense  appetite  may  be  present  in  spite 
of  abundant  feeding. 

Hunger  is  due  to  pronounced  motor  activity  of  the  stomach ;  this 
excites  the  sensory  nerve-terminals  there  (Hertz) ;  these  movements, 
and  therefore  the  sensation  of  hunger,  can  be  appeased  by  filling  the 
stomach  even  with  indigestible  or  non-nutritious  material.  Carlson 
has  recently  shown  that  the  movements  are  reflexly  inhibited  when 
food  enters  the  mouth  and  is  masticated ;  the  nerves  of  taste  act  as 
the  afferent  channel  for  the  reflex ;  hence  the  feeling  of  hunger  passes 
off  long  before  absorption  of  food  begins.  These  observations  confirm 
the  view  that  its  origin  is  a  local  condition  set  up  in  the  stomach  by 
its  condition  of  emptiness,  and  that  it  is  not  immediately  due  to  any 
general  change  in  the  nutrition  of  the  body  as  a  whole.  We  must, 
however,  recognise  that  the  gastric  sense  is  a  complex  one,  as  is 
illustrated  by  the  aversion  for  food  felt  during  monotonous  diets  or 
after  over-feeding,  or  in  the  case  of  certain  articles  of  diet,  but 
the  explanation  of  these  and  similar  phenomena  we  do  not  know. 

Thirst  is  a  sensation  referred  to  the  pharyngeal  region  rather 
than  to  the  stomach,  and  appears,  like  hunger,  to  be  a  protective 
signal,  locally  excited  to  warn  the  living  organism  of  the  necessity 
for  regularity  in  the  intake  of  nutriment.  Although  its  intensity 
increases  with  the  loss  of  water  from  the  body,  it  occurs  normally 
long  before  there  is  any  serious  upset  of  the  normal  relationship  of 
the  water  percentage  of  the  organs  and  tissues,  and  may  be  artifici- 
ally produced  by  drying  of  the  throat ;  it  is  appeased  immediately  by 
the  administration  of  fluid,  and  although  fluids  reach  the  absorbing 
surface  of  the  duodenum  sooner  than  was  formerly  supposed  to  be 
the  case  (see  p.  555),  it  is  unquestionable  that  the  relief  of  thirst  is 
mainly  the  result  of  moistening  the  local  surface,  the  impulses  from 
which  excite  the  sensation.  Very  frequently  thirst  can  be  relieved 
by  letting  the  water  touch  the  pharyngeal  mucous  membrane  without 
its  being  swallowed.  Thirst  which  is  due  to  prolonged  deprivation 
of  water  is  not  a  mere  local  sensation,  but  is  no  doubt  produced  by 
loss  of  water  in  the  tissues,  generally,  exciting  widespread  sensory 
terminations  therein ;  the  bodily  and  mental  anguish  experienced  are 
then  of  an  intense  character. 

The  independence  of  the  two  sensations  hunger  and  thirst  is  well 
illustrated  in  many  diseases,  where  a  loss  of  appetite  occurs  without 
any  corresponding  loss  of  desire  for  fluid. 


CHAPTER     LV 

TASTE   AND   SMELL 

Taste. 

CERTAIN  anatomical  facts  must  be  studied  first  in  connection  with' 
the  tongue,  the  upper  surface  of  which  is  concerned  in  the  reception 
of  taste  stimuli. 

The  tongue  is  a  muscular  organ  covered  by  mucous  membrane. 
The  muscles,  which  form  the  greater  part  of  the  substance  of  the 
tongue  (intrinsic  muscles)  are  termed  linguales ;  and  by  these,  which 
are  attached  to  the  mucous  membrane,  its  smaller  and  more  delicate 
movements  are  performed. 

By  other  muscles  (extrinsic  muscles),  such  as  the  genio-hyoglossus, 
the  styloglossus,  etc.,  the  tongue  is  fixed  to  the  surrounding  parts; 
and  by  these  its  larger  movements  are  performed. 

Its  mucous  membrane  resembles  other  mucous  membranes  in 
essential  points,  but  contains  papillae,  peculiar  to  itself.  The  tongue 
is  also  beset  with  mucous  glands  and  lymphoid  nodules. 

The  lingual  papillce  are  thickly  set  over  the  anterior  two-thirds 
of  its  upper  surface,  or  dorsum  (fig.  478),  and  give  to  it  its  character- 
istic roughness.  Three  principal  varieties  may  be  distinguished, 
namely,  the  (1)  circumvallate,  the  (2)  fungiform,  and  the  (3)  conical 
and  filiform  papillae.  They  are  all  formed  by  a  projection  of  the 
corium  of  the  mucous  membrane,  covered  by  stratified  epithelium ; 
they  contain  special  branches  of  blood-vessels  and  nerves.  The 
corium  in  each  kind  is  studded  by  microscopic  papillae. 

(1.)  Circumvallate. — These  papillae  (fig.  479),  eight  or  ten  in  number, 
are  situate  in  a  V-shaped  line  at  the  base  of  the  tongue  (1,  1,  fig.  478). 
They  are  circular  elevations,  from  ^Vtii  to  TVth  of  an  inch  wide  (1  to 
2  mm.),  each  with  a  slight  central  depression,  and  surrounded  by  a 
circular  moat,  at  the  outside  of  which  again  is  a  slightly  elevated 
ring  or  rampart;  their  walls  contain  taste-buds.  Into  the  moat 
that  surrounds  the  central  tower,  a  few  little  glands  (glands  of 
Ebner)  open.  These  glands  form  a  thin,  watery  secretion. 

779 


780 


TASTE 


[CH.  LV. 


(2.)  Fungiform. — The  fungiform  papillae  (3,  fig.  478)  are  scattered 
chiefly  over  the  sides  and  tip,  and  sparingly  over  the  middle  of  the 


FIG.  478.— Papillar  surface  of  the  tongue,  with  the  fauces  and  tonsils.  1,1,  Circumvallate  papilla;  in 
front  of  2,  the  foramen  caecum  ;  3,  fungiform  papillae  ;  4,  filiform  and  conical  papillae ;  5,  transverse 
and  oblique  rugae  ;  6,  mucous  glands  at  the  base  of  the  tongue  and  in  the  fauces ;  7,  tonsils  ;  8,  part 
of  the  epiglottis ;  9,  median  glosso-epiglottidean  fold  (fraenum  epiglottidis).  (From  Sappey.) 

dorsum,  of  the  tongue ;  their  name  is  derived  from  their  being  shaped 
like  a  puff-ball  fungus.     (See  fig.  480.) 

(3.)  Conical  and  Filiform. — These,  which  are  the  most  abundant 
papillae,  are  scattered  over  the  whole  upper  surface  of  the  tongue, 
but  especially  over  the  middle  of  the  dorsum.  They  vary  in  shape, 
some  being  conical  (simple  or  compound)  and  others  filiform ;  they 
are  covered  by  a  thick  layer  of  epithelium,  which  is  either  arranged 


CH.  LV.] 


THE  LINGUAL  PAPILLA 


781 


over  them,  in  an  imbricated  manner,  or  is  prolonged  from  their  sur- 
face in  the  form  of  fine  stiff  projections  (fig.  481).  In  carnivora  they 
are  developed  into  horny  spines.  From  their  structure,  it  is  likely 
that  these  papillae  have  a  mechanical  and  tactile  function,  rather 
than  that  of  taste;  the  latter 
sense  is  seated  especially  in  the 
other  two  varieties  of  papillae, 
the  circumvallate  and  the  fungi- 
form. 

In  the  circumvallate  papillae 
of  the  tongue  of  man  peculiar 
structures  known  as  taste-buds 
are  found.  They  are  of  an  oval 
shape,  and  consist  of  a  number 
of  closely  packed,  very  narrow 
and  fusiform,  cells  (gustatory 
cells).  This  central  core  (  of 

gustatory  Cells    IS   enclosed  in   a 

single  layer  of  broader  fusiform 

cells  (encasing  cells).    The  gustatory  cells  terminate  in  fine  stiff  spikes 

which  project  on  the  free  surface  (fig.  482,  a). 

Taste -buds  are  also  scattered  over  the  posterior  third  of  the 
tongue,  the  palate  and  the  pharynx,  as  low  as  the  posterior  (laryngeal) 


FIG.  479.— Vertical  section  of  a  circumvallate  papilla 
of  the  calf.  1  and  3,  Epithelial  layers  covering  it ; 

<  2,  taste-buds  ;  4  and  4',  duct  of  serous  gland  open- 

•  ing  out  into  the  pit  in  which  papilla  is  situated  ; 

c  5  and  6,  nerves  ramifying  within  the  papilla. 
(Bngelmann.) 


Fio.  480.— Surface  and  section  of  the  fungiform  papillae.  A.  The  surface  of  a  fungiform  papilla,  partially 
denuded  of  its  epithelium ;  p,  secondary  papillae ;  e,  epithelium.  B.  Section  of  a  fungifonn  papilla 
with  the  blood-vessels  injected ;  a,  artery ;  v,  vein ;  c,  capillary  loops  of  similar  papillae  in  the 
neighbouring  structure  of  the  tongue ;  d,  capillary  loops  of  the  secondary  papillae ;  e,  epithelium. 
(From  Kolliker,  after  Todd  and  Bowman.) 

surface  of  the  epiglottis.     The  gustatory  cells  in  the  interior  of  the 
taste-buds  are  surrounded  by  arborisations  of  nerve-fibres. 

The  arrangement  of  papillae,  taste-buds,  etc.,  varies  a  good  deal  in  different 
animals.  The  papilla  foliata  of  the  rabbit's  tongue  consists  of  a  number  of  closely 
packed  papillae,  similar  to  the  circumvallate  papillae  of  man  ;  this  forms  a  con- 
venient source  for  the  histological  demonstration  of  taste-buds. 


782 


TASTE 


[OH.  LV. 


The  middle  of  the  dorsum  of  the  tongue  is  but  feebly  endowed 
with  the  sense  of  taste;   the  tip  and  margins,  and  especially  the 

posterior  third  of  the  dorsum 
(i.e.,  in  the  region  of  the  taste- 
buds),  possess  this  faculty. 
The  anterior  part  of  the 
tongue  is  supplied  by  the 
lingual  branch  of  the  fifth 


Fio.  482. — Taste-bud  from  dog's  epiglottis 
(laryngeal  surface  near  the  base),  precisely 
similar  in  structure  to  those  found  in 
the  tongue,  a,  Depression  in  epithelium 
over  bud;  below  the  letter  are  seen  the 
fine  hair-like  processes  in  which  the  cells 
terminate;  c,  two  nuclei  of  the  axial 
(gustatory)  cells.  The  more  superficial 
nuclei  belong  to  the  superficial  (encasing) 
cells ;  the  converging  lines  indicate  the 
fusiform  shape  of  the  encasing  cells,  x  400. 
(Schofield.) 


FIG.  481.— Filiform  papillae,  one  with  epithelium, 
the  other  without.  >\6-. — p,  The  substance  of  the 
papillae  dividing  at  their  upper  extremities  into 
secondary  papillae ;  a,  artery,  and  v,  vein,  dividing 
into  capillary  loops ;  e,  epithelial  covering,  lamin- 
ated between  the  papillae,  but  extended  into  hair- 
like  processes,  /,  from  the  extremities  of  the 
secondary  papillse.  (From  KiJlliker,  after  Todd 
and  Bowman.) 


nerve  and  the  chorda  tym- 
pani,  and  the  posterior  third 
by  the  glosso  -  pharyngeal 
nerve.  Considerable  discus- 
sion has  arisen  whether  there 
is  more  than  one  nerve  of 

taste.  The  view  generally  held  is  that  the  glosso-pharyngeal  nerve 
is  the  nerve  of  taste,  and  the  lingual  the  nerve  of  tactile  sensa- 
tion. Nevertheless,  the  lingual  and  the  chorda  tympani  do  con- 
tain taste-fibres,  which  probably  take  origin  from  the  cells  of  the 
geniculate  ganglion;  the  central  axons  of  these  cells  pass  by  the 
pars  intermedia  to  the  sensory  nucleus  of  the  glosso-pharyngeal 
nerve.  Gowers  holds  that  the  fifth  nerve  is  the  only  nerve  of  taste, 
and  has  recorded  a  case  of  loss  of  taste  where  the  fifth  nerve  alone 
was  the  seat  of  disease ;  other  cases,  however,  do  not  support  this 
view. 


CH.  LV.]  THE   NERVE   OF   SMELL  783 

Tastes  may  be  classified  into — 

1.  Sweet.  2.  Bitter. 

3.  Acid  or  Sour.  4.  Salt. 

Whether  alkaline  and  metallic  tastes  are  elementary,  is  as  yet 
undecided.  All  the  above  affect  to  a  varying  extent  the  nerves  of 
tactile  sense  as  well  of  those  of  touch  proper,  sweet  having  the  least, 
acids  the  most  marked  action  upon  the  latter.  Sweet  tastes  are  best 
appreciated  by  the  tip,  acid  at  the  side,  and  bitter  tastes  at  the 
back  of  the  tongue. 

The  substance  to  be  tasted  must  be  dissolved;  here  there  is  a 
striking  contrast  to  the  sense  of  smell ;  flavours  are  really  odours. 
In  testing  the  sense  of  taste  in  a  patient,  the  tongue  should  be 
protruded,  and  drops  of  the  substance  to  be  tasted  applied  with 
a  camel's  hair  brush  to  the  different  parts;  the  subject  of  the 
experiment  must  signify  his  sensations  by  signs,  for  if  he  with- 
draws the  tongue  to  speak,  the  material  gets  widely  spread.  The 
more  concentrated  the  solution,  and  the  larger  the  surface  acted  on, 
the  more  intense  is  the  taste;  some  tastes  are  perceived  more 
rapidly  than  others,  saline  tastes  the  most  rapidly  of  all  The  best 
temperature  of  the  substance  to  be  tasted  is  from  10°  to  35°  C. 
Very  high  or  very  low  temperatures  deaden  the  sense. 

Individual  papillae,  when  thus  treated  with  various  solutions,  show 
great  diversity:  from  some  only  one  or  two  tastes  can  be  evoked, 
from  others  all  four.  The  papillae  may  also  be  stimulated  electrically. 

Cocaine  and  gymnemic  acid,  prepared  from  the  leaves  of  the 
plant  Gymnema  sylvestre,  act  deleteriously,  chiefly  on  the  bitter 
and  sweet  tastes ;  cocaine  abolishes  especially  the  bitter,  gymnemic 
acid  especially  the  sweet,  leaving  the  salt  and  acid  tastes  almost 
untouched. 

It  will  thus  be  seen  that  there  are  many  facts  pointing  to  the 
conclusion,  that  the  varieties  of  gustatory  like  "those  of  cutaneous 
sensation  are  due  to  the  stimulation  of  different  end-organs. 

When  diluted  sweet  and  salt  solutions  are  simultaneously  applied 
to  the  tongue,  they  tend  to  neutralise  one  another,  but  a  true  indifferent 
point  is  difficult  or  impossible  to  reach.  Sweet  and  bitter,  sweet 
and  acid  liquids  are  antagonistic  to  a  similar  but  less  perfect 
extent.  Contrast-effects  of  one  taste  upon  another  are  matters  of 
common  observation,  but  can  only  be  experimentally  investigated 
with  difficulty. 

Smell. 

The  entrance  to  the  nasal  cavity  is  lined  with  a  mucous  membrane 
closely  resembling  the  skin.  The  greater  part  of  the  rest  of  the 
cavity  is  lined  with  ciliated  epitheMum;  the  corium  is  thick  and 


784 


SMELL 


[CH.  LV. 


FIG.  483.— Cells  from  the  olfactory  region  of 
the  rabbit,  st,  Supporting  cells ;  r,  r', 
olfactorial  cells  ;  /,  ciliated  cells ;  s,  cilia- 
like  processes;  b,  cells  from  Bowman's 
glands.  (Stohr.) 


contains  numerous  mucous  glands.  The  olfactory  region  in  man  is 
limited  to  a  portion  of  the  membrane  covering  the  upper  turbinal  bone, 
and  the  adjacent  portion  of  the  nasal  septum ;  it  is  only  245  square 
millimetres  in  area.  The  cells  of  the  epithelium  here  are  of  several 
kinds : — first,  columnar  cells  not  ciliated  (fig.  483,  st),  with  the  broad 

end  at  the  surface,  and  below 
tapering  into  an  irregular  branched 
process  or  processes,  the  termina- 
tions of  which  pass  into  the  next 
layer:  the  second  kind  of  cell  (fig. 
483,  r)  consists  of  a  small  cell  body 
with  large  spherical  nucleus,  situ- 
ated between  the  ends  of  the  first 
kind  of  cell,  and  sending  upwards 
a  process  to  the  surface  between 
the  cells  of  the  first  kind,  and  from 
the  other  pole  of  the  nucleus  a  pro- 
cess towards  the  corium.  The  latter 
process  is  very  delicate,  and  may 
be  varicose.  The  upper  process  is 
prolonged  beyond  the  surface,  where 
it  becomes  stiff,  and  in  some  animals,  such  as  the  frog,  is  provided 
with  hairs.  These  cells,  which  are  called  olfactorial  cells,  are  numerous, 
and  the  nuclei  of  the  cells  not  being  on  the  same  level,  a  compara- 
tively thick  nuclear  layer  is  the  result.  They  are  in  reality  bipolar 
nerve-cells.  In  the  corium  are  a  number  of  serous  glands  called 
Bowman's  glands.  They  open  upon  the  surface  by  fine  ducts  passing 
up  between  the  epithelium  cells. 

The  distribution  of  the  olfactory  nerves  which  penetrate  the 
cribriform  plate  of  the  ethmoid  bone  and  pass  from  this  region  to 
the  olfactory  bulb  is  shown  in  fig.  484.  The  nerve-fibres  are 
the  central  axons  of  the  bipolar  nerve-cells  we  have  termed  olfac- 
torial ;  the  columnar  cells  between  these  act  as  supports  to  them. 

The  olfactory  tract  is  an  outgrowth  of  the  brain,  which  is 
originally  hollow,  and  remains  so  in  many  animals ;  in  man  the 
cavity  is  obliterated,  and  the  centre  is  occupied  by  neuroglia : 
outside  this  the  white  fibres  lie,  and  a  thin  superficial  layer  of 
neuroglia  covers  these.  The  three  "roots"  of  the  olfactory  tract 
have  been  traced  to  the  uncinate  gyrus  and  hippocampal  regions  of 
the  same  side  of  the  brain,  which  is  the  portion  experimentally  found 
to  be  associated  with  the  reception  of  olfactory  impulses  (see 
pp.  698  and  738).  From  the  cells  of  the  grey  matter  here  fibres  pass 
by  a  complex  path  to  the  corresponding  regions  of  the  opposite 
side.  There  is  also  a  communication  via  the  corpora  mammillaria 
with  the  optic  thalamus  and  te^mentum  of  the  mid-brain. 


CH.  LY.] 


THE  OLFACTOKY  APPARATUS 


785 


"    The  olfactory  bulb  has  a  more  complicated  structure ;  above  there 
is  first  a  continuation  of  the  olfactory  tract  (white  fibres  enclosing 


ynr™ 


FIG.  484. — Nerves  of  the  septum  nasi,  seen  from  the  right  side.  §. — I,  the  olfactory  bulb;  ],  the 
olfactory  nerves  passing  through  the  foramina  of  the  cribriform  plate,  and  descending  to  be  distri- 
buted on  the  septum  ;  2,  the  internal  or  septal  twig  of  the  nasal  branch  of  the  ophthalmic  nerve ;  3, 
naso-palatine  nerves.  (Prom  Sappey,  after  Hirschfeld  and  Leveille.) 

neuroglia);  below  this  four  layers  are  distinguishable;  they  are 
shown  in  the  accompanying  diagram  from  Eamon  y  Cajal's  work, 
the  histological  method  used  being  Golgi's. 


FIG.  485.— Nervous  mechanism  of  the  olfactory  apparatus.  A,  bipolar  cells  of  the  olfactory  apparatus 
(Max  Schultze's  olfactorial  cells) ;  B,  olfactory  glomeruli ;  C,  mitral  cells ;  D,  granule  of  white 
layer;  E,  external  root  of  the  olfactory  tract;  F,  grey  matter  of  the  sphenoidal  region  of  the 
cortex  ;  a,  small  cell  of  the  mitral  layer ;  5,  basket  of  a  glomerulus  ;  c,  spiny  basket  of  a  granule  ; 
e,  collateral  of  the  axis-cylinder  process  of  a  mitral  cell ;  /,  collaterals  terminating  in  the  molecular 
layer  of  the  frontal  and  sphenoidal  convolutions;  g,  superficial  triangular  cells  of  the  cortex; 
h,  supporting  epithelium  cells  of  the  olfactory  mucous  membrane.  (Ramon  y  Cajal.) 

(1)  A  layer  of  white  fibres  containing  numerous  small  cells,  or 
"granules"  (D). 


786  SMELL  [CH.  LV. 

(2)  A  layer  of  large  nerve-cells  called  "  mitral  cells "  (c),  with 
smaller  cells  (a)  mixed  with  them.     The  axis-cylinder  processes  of 
these  cells  pass  up  into  the  layer  above  and   eventually  become 
fibres  of  the  olfactory  tract  E,  which  passes  to  the  grey  matter  of 
the  base  of  the  brain  F.     They  give  off  numerous  collaterals  on  the 
way  (e,f). 

(3)  The  layer  of  olfactory  glomeruli  (B).     Each  glomerulus  is  a 
basket-work  of  fibrils  derived  on  the  one  hand  from  the  terminal 
arborisations  of  the  mitral   cells,  and   on   the   other  from   similar 
arborisations  of  the  non-medullated  fibres  which  form  the  next  layer. 

(4)  The  layer  of  olfactory  nerve-fibres. — These  are  non-medullated ; 
they  continue  upwards  the  bipolar  olfactory  cells,  which  are  placed 
among  the  epithelial  cells  of  the  mucous  membrane. 

Animals  may  be  divided  into  three  classes : — those  which,  like  the 
porpoise,  have  no  sense  of  smell  (anosmatic) ;  those  which  possess  it  in 
comparatively  feeble  degree  (man,  most  primates,  monotremes,  and 
some  cetacea) ;  these  are  called  microsmatic.  In  man  the  thickness 
of  the  olfactory  membrane  is  only  O06  mm.  Most  mammals  are  in 
contradistinction  macrosmatic,  the  thickness  of  the  membrane  being 
O'l  mm.  or  more,  and  its  area  larger. 

The  mucous  membrane  must  be  neither  too  dry  nor  too  moist ;  if 
we  have  a  cold  we  are  unable  to  smell  odours  or  appreciate  flavours 
(which  are  really  odours).  When  liquids  are  poured  into  the  nose, 
their  smell  is  imperceptible,  as  they  damage  the  olfactory  epithelium, 
owing  to  the  difference  of  osmotic  pressure.  But  even  if  a  "  normal " 
saline  solution  of  an  odorous  substance  be  substituted,  the  sense  of 
smell  is  still  lost  so  long  as  air-bubbles  are  carefully  excluded  from 
the  nasal  cavity.  It  is  therefore  necessary  that  odorous  substances 
should  be  in  a  gaseous  state  in  order  to  act  upon  the  olfactory 
nerve-endings ;  they  are  normally  conveyed  to  the  olfactory  surface 
by  the  air  currents  passing  through  the  nose. 

Generally,  the  odours  of  homologous  series  of  compounds  increase 
in  intensity  with  increase  of  molecular  weight,  but  bodies  of  very  low 
molecular  weight  are  odourless,  while  vapours  of  very  high  molecular 
weight,  which  escape  and  diffuse  slowly,  have  little  or  no  smell.  A  slight 
change  in  chemical  constitution  may  produce  marked  alteration  in 
the  character  of  the  odour  of  a  substance ;  certain  modes  of  atomic 
grouping  within  the  molecule  appear  to  be  more  odoriferous  than 
others.  Attempts  have  been  made  to  discover  the  elementary  sensa- 
tions of  smell,  but  hitherto  with  scant  success.  Many  odours  have 
unquestionably  a  complex  physiological  effect.  For  example,  when 
nitrobenzol  is  held  before  the  nose,  it  yields  first  the  smell  of 
heliotrope,  next  the  smell  of  bitter  almonds,  and  finally  the  smell 
of  benzene ;  just  as  if  different  end  -  organs  became  successively 
fatigued.  Some  substances  have  a  very  different  smell  according 


CH.  LV.]  OLFACTORY   SENSATIONS  787 

to  their  concentration.  Chemical  dissociation,  too,  unquestionably 
plays  a  prominent  part. 

Nevertheless,  there  are  certain  observations  which  indicate  the 
existence  of  primary  sensations  of  smell.  First,  some  persons  are 
congenitally  insensible  to  one  or  more  odours,  but  yet  smell  others 
quite  normally.  Hydrocyanic  acid,  mignonette,  violet,  vanilla, 
benzoin,  are  substances  which  appear  to  certain  people  to  have  no 
smell.  Secondly,  some  odorous  bodies,  when  simultaneously  given, 
antagonise  one  another;  others  produce  a  mixed  smell.  Thirdly, 
fatigue  of  the  epithelium  with  one  odour  will  modify  or  abolish  the 
effect  of  some  smells,  but  will  leave  that  of  others  untouched. 

The  delicacy  of  the  sense  of  smell  is  most  remarkable  even  in  man. 
Valentin  calculates  that  even  100  0Q0  000  of  a  grain  of  musk  can  be  dis- 
tinctly smelled.  Solutions  of  camphor  afford  a  good  means  of  testing 
olfactory  acuity.  Two  tubes  of  camphor  solution  are  presented  to  the 
subject  along  with  two  tubes  of  water,  and  the  former  pair  is  replaced 
with  weaker  and  weaker  solutions  until  it  is  indistinguishable  from 
the  tubes  containing  water.  Pungent  substances,  such  as  ammonia, 
are  unsuited  for  olfactometrical  experiment.  They  stimulate  the 
endings  of  the  fifth  as  well  as  those  of  the  olfactory  nerve. 


CHAPTEK  LYI 

HEARING 

Anatomy  of  the  Ear. 

THE  Organ  of  Hearing  (tig.  486)  is  divided  into  three  parts,  (1)  the 
external,  (2)  the  middle,  and  (3)  the  internal  ear. 

External  Ear. — The  external  ear  consists  of  the  pinna  and  the 
external  auditory  meatus.  The  central  hollow  of  the  former 
is  named  the  concha.  The  auditory  canal,  with  a  slight 
arch  directed  upwards,  passes  inwards  and  a  little  forwards  to 
the  membrana  tympani,  to  which  it  thus  serves  to  convey  the 
vibrating  air. 

Middle  Ear  or  Tympanum. — The  middle  ear,  or  tympanum  or 
drum  (3,  fig.  486),  is  separated  by  the  membrana  tympani  from 
the  external  auditory  meatus.  It  is  a  cavity  which  communi- 
cates posteriorly  with  the  mastoid  cells  in  the  mastoid  pro- 
cess of  the  temporal  bone;  but  its  only  opening  to  the  external 
air  is  through  the  Eustachian  tube  (4,  fig.  486).  The  walls  of  the 
tympanum  are  osseous,  except  where  apertures  in  them  are  closed 
with  membrane,  as  at  the  fenestra  rotunda,  and  fenestra  ovalis,  and 
at  the  outer  part  where  the  bone  is  replaced  by  the  membrana 
tympani  Its  cavity  is  lined  with  mucous  membrane,  which  is 
continuous  through  the  Eustachian  tube  with  that  of  the  pharynx. 
A  chain  of  small  bones  extends  from  the  membrana  tympani  to 
the  fenestra  ovalis. 

The  membrana  tympani  is  placed  in  a  slanting  direction  at  the 
bottom  of  the  external  auditory  canal,  and  consists  of  fibres,  some 
running  radially,  some  circularly ;  its  margin  is  set  in  a  bony  groove ; 
its  outer  surface  is  covered  with  a  continuation  of  the  cutaneous 
lining  of  the  auditory  canal,  its  inner  surface  with  the  mucous 
membrane  of  the  tympanum. 

The  ossicles  are  three  in  number;  named  malleus,  incus,  and 
stapes.  The  malleus,  or  hammer-bone,  has  a  long  slightly-curved 
process,  called  its  handle,  which  is  inserted  vertically  between  the 

788 


CH.  LVL] 


ANATOMY  OF  THE   EAR 


789 


FIG.  486.— Diagrammatic  view  from  before  of  the  parts  composing  the  organ  of  hearing  of  the  left  side. 
The  temporal  bone  of  the  left  side,  with  the  accompanying  soft  parts,  has  been  detached  from  the 
head,  and  a  section  has  been  carried  through  it  transversely,  so  as  to  remove  the  front  of  the 
meatus  externus,  half  the  tympanic  membrane,  the  upper  and  anterior  wall  of  the  tympanum  and 
Eustachian  tube.  The  meatus  internus  has  also  been  opened,  and  the  bony  labyrinth  exposed  by 
the  removal  of  the  surrounding  parts  of  the  petrous  bone.  1 ,  The  pinna  and  lobe ;  2,  meatus 
externus  ;  2',  membrana  tympani ;  3,  cavity  of  the  tympanum  ;  3',  its  opening  backwards  into  the 
mastoid  cells  ;  between  3  and  3',  the  chain  of  small  bones  ;  4,  Eustachian  tube  ;  5,  meatus  internus, 
containing  the  facial  (uppermost)  and  the  auditory  nerves ;  6,  placed  on  the  vestibule  of  the  laby- 
rinth above  the  fenestra  ovalis  ;  a,  apex  of  the  petrous  bone ;  b,  internal  carotid  artery  :  c,  styloid 
process  ;  d,  facial  nerve  issuing  from  the  stylo-mastoid  foramen ;  e,  mastoid  process ;  /,  squamous 
part  of  the  bone  covered  by  integument,  etc.  (Arnold.) 


Fio.  487.— The  hammer- 
bone  or  malleus,  seen 
from  the  front.  1,  The 
head ;  2,  neck ;  3, 
short  process ;  4, 
handle.  (Schwalbe.) 


Fio.  488. — The  incus,  or  anvil-bone. 
1,  Body;  2,  ridged  articulation 
for  the  malleus;  4,  processus 
brevis,  with  5,  rough  articular 
surface  for  ligament  of  incus ; 
6,  processus  magnus,  with  articu- 
lating surface  for  stapes;  7,  nu- 
trient foramen.  (Schwalbe.) 


Fio.  489.— The  stapes,  or 
stirrup  -  bone.  1,  Base; 
2  and  3,  arch;  4,  head 
of  bone,  which  articu- 
lates  with  orbicular 
process  of  the  incus ; 
5,  constricted  part  of 
neck;  6,  one  of  the 
crura.  (Schwalbe.) 


790  HEARING  [CH.  LVI. 

layers  of  the  membrana  tympani.  The  head  of  the  malleus  is 
irregularly  rounded ;  its  neck,  or  the  line  of  boundary  between  the 
head  and  the  handle,  supports  two  processes:  a  short  conical  one, 
and  a  slender  one,  processus  gracilis,  which  extends  forwards,  and  is 
attached  to  the  wall  of  the  cavity  at  the  G-laserian  fissure.  The 
incus,  or  anvil-bone,  shaped  like  a  bicuspid  molar  tooth,  is  articulated 
by  its  broader  part,  corresponding  with  the  surface  of  the  crown  of 
the  tooth,  to  the  malleus.  Of  its  two  fang-like  processes,  one, 
directed  backwards,  has  a  free  end  attached  by  ligament  to  a  depres- 
sion in  the  mastoid  bone ;  the  other,  curved  downwards,  longer  and 
more  pointed,  articulates  by  means  of  a  roundish  tubercle,  formerly 

called  os  orbiculare,  with  the  stapes, 
a  little  bone  shaped  like  a  stirrup, 
of  which  the  base  fits  into  the 
membrane  of  the  fenestra  ovalis. 

The  muscles  of  the  tympanum 
are  two  in  number.  The  tensor 
tympani  arises  from  the  cartila- 
ginous end  of  the  Eustachian  tube 
and  the  adjoining  surface  of  the 
sphenoid,  and  from  the  sides  of 
the  canal  in  which  the  muscle  lies ; 
the  tendon  of  the  muscle  bends  at 
FIG.  490.— interior  view  of  the  tympanum,  with  nearly  a  right  angle  over  the  end 

membrana  tympani  and  bones  in  natural  posi-  ,,     it*                                           ,,         .» 

tion.    1,  Membrana  tympani ;  2,  Eustachian  01     the     prOCCSSUS    COCIllearilOrmiS, 

tube;  3,  tensor  tympani  muscle  ;  4,lig.  mallei  ~nr]    •_  inQprfp^    \r\tr\  f"hp>  irmek-r  -r»avf 

exter.;  5,  lig.  mallei  super.;  6,  chorda-tympani  ana  1S  inserted   into  W16  inner  part 

nerve;   a,  b,  and  c,  sinuses  about  ossicles.  Of  tf&Q  handle  of  the  malleUS        The 

(Schwalbe.)  ,.          .                   '           ,          ...  . 

stapedius  is  concealed  within  a 

canal  in  the  bone  in  front  of  the  aqueductus  Fallopii.  Its  tendon 
is  inserted  into  the  neck  of  the  stapes  posteriorly. 

The  Internal  Bar. — The  proper  organ  of  hearing  is  formed  by  the 
distribution  of  the  auditory  nerve,  within  the  internal  ear,  or  laby- 
rinth, a  set  of  cavities  within  the  petrous  portion  of  the  temporal 
bone.  The  bone  which  forms  the  walls  of  these  cavities  is  denser 
than  that  around  it,  and  forms  the  osseous  labyrinth  ;  the  membrane 
within  the  cavities  forms  the  membranous  labyrinth.  The  mem- 
branous labyrinth  contains  a  fluid  called  endolymph ;  while  outside 
it,  between  it  and  the  osseous  labyrinth,  is  a  fluid  called  perilymph. 
This  fluid  is  not  pure  lymph,  as  it  contains  mucin. 

The  Osseous  Labyrinth  consists  of  three  principal  parts,  namely, 
the  vestibule,  the  cochlea,  and  the  semicircular  canals. 

The  vestibule  is  the  middle  cavity  of  the  labyrinth,  and  the 
central  chamber  of  the  auditory  apparatus.  It  presents,  in  its 
inner  wall,  several  openings  for  the  entrance  of  the  divisions  of  the 
auditory  nerve ;  in  its  outer  wall,  the  fenestra  ovalis  (2,  fig.  49  la), 


CH.  LVI.] 


THE   COCHLEA 


791 


an  opening  filled  by  membrane,  in  which  is  inserted  the  base  of  the 
stapes ;  in  its  posterior  and  superior  walls,  five  openings  by  which 
the  semicircular  canals  communicate  with  it:  in  its  anterior  wall, 


FIG.  491a. — Right  bony  labyrinth,  viewed 
from  the  outer  side.  The  specimen 
here  represented  is  prepared  by  sepa- 
rating piecemeal  the  looser  substance 
of  the  petrous  bone  from  the  dense 
walls  which  immediately  enclose  the 
labyrinth.  1,  The  vestibule;  2,  fen- 
estra  ovalis;  3,  superior  semicircular 
canal ;  4,  horizontal  or  external  canal ; 
5,  posterior  canal;  *,  ampullae  of  the 
semicircular  canals;  5,  first  turn  of 
the  cochlea ;  7,  second  turn ;  8,  apex ; 
9,  fenestra  rotunda.  The  smaller  figure 
in  outline  below  shows  the  natural  size. 

2i 

-~  •     (Summering.) 


FIG.  491&.— View  of  the  interior  of  the  left 
labyrinth.  The  bony  wall  of  the  laby- 
rinth  is  removed  superiorly  and  exter- 
nally.  1,  Fovea  hemielliptica ;  2,  fovea 
hemispherica ;  3,  common  opening  of 
the  superior  and  posterior  semicircular 
canals;  4,  opening  of  the  aqueduct  of 
the  vestibule;  5,  the  superior;  6,  the 
posterior,  and  7,  the  external  semicir- 
cular  canals ;  8,  spiral  tube  of  the 
cochlea  (scala  tympani);  9,  opening  of 
the  aqueduct  of  the  cochlea;  10,  placed 
on  the  lamina  spiralis  in  the  scala  ves- 


an  opening  leading  into  the  cochlea.  The  semicircular  canals  are 
described  in  Chapter  LI. 

The  Membranous  Labyrinth  corresponds  in  general  form  with 
the  osseous  labyrinth.  The  vestibule  contains  two  membranous 
sacs,  named  the  utricle  and  the  saccule  (fig.  492) ;  the  utricle  com- 
municates with  the  three  membranous  semicircular  canals;  the 
saccule  communicates  with  the  utricle  and  with  the  canal  of  the 
cochlea.  The  vestibular  division  of  the  auditory  nerve  is  distributed 
to  the  five  spots  shown  in  the  diagram,  namely,  the  maculae  of  utricle 
and  saccule,  and  the  cristae  of  the  semicircular  canals.  The  cochlear 
division  of  the  auditory  nerve  is  distributed  to  the  whole  length  of 
the  canal  of  the  cochlea. 

The  Cochlea. — This  is  shaped  like  a  snail's  shell.  It  is  traversed 
by  a  central  column  or  modiolus,  around  which  a  spiral  canal  winds 
with  two  and  a  half  turns  from  base  to  apex.  It  is  seen  in 
vertical  section  (fig.  493)  that  this  canal  is  divided  partly  by  bone 
(the  spiral  lamina),  partly  by  membrane  (the  basilar  membrane), 


792 


HEARING 


[CH.  LVI. 


into  two  spiral   staircases    or  scaled,  the  scala   tympani  and   scala 
vestibuli  (fig.  493).      The    scala   vestibuli   is    separated    from   the 

tympanum  by  the  membrane  of  the 
fenestra  ovalis,  and  the  scali  tympani  is 
similarly  separated  from  the  tympanum 
by  the  membrane  of  the  fenestra  rotunda. 


.E. 


C.R. 


FIG.  492. — Diagram  of  the  right  mem- 
branous labyrinth.  U,  utricle,  into 
which  the  three  semicircular  canals 
open ;  S,  saccule,  communicating 
with  the  cochlea  (C)  by  C.R.,  the 
canalis  reunions,  and  with  the  utricle 
by  a  canal  having  on  it  an  enlarge- 
ment, the  saccus  endolymphaticua 
(S.B.).  The  black  shading  repre- 
sents the  places  of  termination  of 
the  auditory  nerve,  namely,  in  the 
maculae  of  the  utricle  and  saccule ; 
the  cristae  in  the  ampullary  ends  of 
the  three  semicircular  canals ;  and 
in  the  whole  length  of  the  canal  of 
the  cochlea.  (After  Schiifer.) 


FIG.  493.— View  of  the  osseous  cochlea 
divided  through  the  middle.  1,  Central 
canal  of  the  modiolus  ;  2,  lamina  spiralis 
ossea ;  3,  scala  tympani ;  4,  scala  vesti- 
buli ;  5,  porous  substance  of  the  modiolus 
near  one  of  the  sections  of  the  canalis 
spiralis  modioli.  f .  (Arnold.) 


Both  scalse  are  filled  with  perilymph. 
The  basilar  membrane  increases  in  breadth 
from  the  base  towards  the  apex  of  the 
cochlea.  It  contains  fibres  (about  24,000 
in  all)  imbedded  in  a  homogeneous  matrix, 
and  running  radially,  from  the  spiral  lamina  to  the  spiral  ligament, 
where  its  other  end  is  again  attached  to  the  bone.  At  the 

apex  of  the  cochlea,  the 
lamina  ends  in  a  small  hamu- 
lus,  the  inner  and  concave 
part  of  which  being  detached 
from  the  summit  of  the 
modiolus,  leaves  a  small  aper- 
ture named  the  helicotrema, 
by  which  the  two  scalae,  sepa- 
rated in  all  the  rest  of  their 
length,  communicate. 

Besides  the  scala  vestibuli 
and  scala  tympani,  there  is 
a  third  space  between  them, 
called  scala  media  or  canal  of 

,-i  M     n-t-i        f  nn    fi        <tr\i\        T 
t/ie  COCflUa  (GO,  tig.  494).       In 

qppf-irm  if  ia  fr inn  mi  lav  if  a 
Sectia  «  *S  triangular,  itS 

external     Wall    beinef1    formed 
,,  ,,        „      ,    &  .  . 

by  the  wall  of  the  cochlea, 
its   upper    wall   (separating  it   from    the   scala   vestibuli)   by  the 


FIG.  494.— Section  through  one  of  the  coils  of  the  cochlea 
(diagrammatic).  ST,  scala  tympani ;  SV,  scala  vesti- 
buli ;  CC,  canalis  cochlea  or  canalis  membranaceus  ; 
R,  membrane  of  Reissner ;  Iso,  lamina  spiralis  ossea ; 
Us,  limbus  laminae  spiralis;  ss,  sulcus  spiralis;  nc, 
cochlear  nerve;  gs,  ganglion  spirale;  t,  membrana 
tectoria  (below  the  membrana  tectoria  is  the  lamina 
reticularis) ;  &,  membrana  basilaris  ;  Co,  rods  of  Corti ; 
Isp,  ligamentum  spirale.  (Quain.) 


CH.  LYL] 


THE  ORGAN  OF  CORTI 


793 


membrane  of  Keissner,  and  its  lower  wall  (separating  it  from  the 
scala  tympani)  by  the  basilar  membrane,  these  two  meeting  at 
the  outer  edge  of  the  bony  lamina  spiralis.  Following  the  turns  of 
the  cochlea  to  its  apex,  the  scala  media  there  terminates  blindly; 
at  the  base  of  the  cochlea  a  narrow  passage  (canalis  reuniens)  unites 
it  with  the  saccule.  The  scala  media  (like  the  rest  of  the  membranous 
labyrinth)  contains  endolymph. 

Organ  of  Corti. — Upon  the  basilar  membrane  are  arranged  cells 
of  various  shapes.  About  midway  between  the  outer  edge  of  the 
lamina  spiralis  and  the  outer  wall  of  the  cochlea  are  situated  the 
rods  of  Corti.  Viewed  sideways,  they  are  seen  to  consist  of  an 
external  and  internal  pillar,  each  rising  from  an  expanded  foot  or 
base  attached  to  the  basilar  membrane  (o,  n,  fig.  495).  They  slant 


u 


FIG.  495.— Vertical  section  of  the  organ  of  Corti  from  the  dog.  1  to  2,  Homogeneous  layer  of  the 
membraria  basilaris ;  u,  vestibular  layer ;  v,  tympanal  layer,  with  nuclei  and  protoplasm ;  a,  pro- 
longation of  tympanal  periosteum  of  lamina  spiralis  ossea ;  c,  thickened  commencement  of  the 
membrana  basilaris  near  the  point  of  perforation  of  the  nerves  h ;  d,  blood-vessel  (vas  spirale) ;  e, 
blood-vessel;  /,  nerves  ;  g,  the  epithelium  of  the  sulcus  spiralis  internus;  i,  internal  hair-cell,  with 
basal  process  k,  surrounded  with  nuclei  and  protoplasm  (of  the  granular  layer),  into  which  the 
nerve-nbres  radiate ;  I,  hairs  of  the  internal  hair-cell ;  n,  base  or  foot  of  inner  pillar  of  organ  of  Corti ; 
TO,  head  of  the  same  uniting  with  the  corresponding  part  of  an  external  pillar,  whose  under  half  is 
missing,  while  the  next  pillar  beyond,  o,  presents  both  middle  portion  and  base ;  r,  s,  d,  three 
external  hair-cells  ;  t,  bases  of  two  neighbouring  hair  or  tufted  cells  ;  x,  supporting  cell  of  Belters; 
w,  nerve-fibre  arborising  round-  the  nrst  of  the  external  hair-cells ;  I  I  to  I,  lamina  reticularis. 
x  800.  (Waldeyer.) 

inwards  towards  each  other,  and  each  ends  in  a  swelling  termed  the 
head  ;  the  head  of  the  inner  pillar  overlies  that  of  the  outer.  Each 
pair  of  pillars  forms  a  pointed  roof  arching  over  a  space,  and  by  a 
succession  of  them  a  tunnel  is  formed. 

There  are  about  3000  of  these  pairs  of  pillars,  in  proceeding  from 
the  base  of  the  cochlea  towards  its  apex.  They  are  found  pro- 
gressively to  increase  in  length,  and  become  more  oblique ;  in  other 
words,  the  tunnel  becomes  wider,  but  diminishes  in  height  as  we 
approach  the  apex  of  the  cochlea.  Leaning  against  the  rods  of  Corti 
are  certain  other  cells  called  hair-cells,  which  terminate  in  small 


794  HEARING  [CH.    LYI. 

hair-like  processes.  There  are  several  rows  of  these  on  the  outer 
and  one  row  on  the  inner  side.  Between  them  are  certain  sup- 
porting cells  called  cells  of  Deiters  (fig.  495,  x).  This  structure  rests 
upon  the  basilar  membrane ;  it  is  roofed  in  by  a  fenestrated  mem- 
brane or  lamina  reticularis  into  the  fenestrse  of  which  the  tops  of 
the  various  rods  and  cells  are  received.  When  viewed  from  above, 
the  organ  of  Corti  shows  a  remarkable  resemblance  to  the  key- 
board of  a  piano.  The  top  of  the  organ  is  roofed  by  the  membrana 
tectoria  (fig.  494,  t)  which  extends  from  the  end  of  the  limbus 
(Us,  fig.  494),  a  connective-tissue  structure  on  the  spiral  lamina. 
The  spiral  ganglion  from  which  the  cochlear  nerve-fibres  originate  is 
situated  in  the  spiral  lamina.  The  peripheral  axons  of  its  bipolar 
cells  arborise  around  the  hair-cells  of  the  organ  of  Corti :  the  central 
axons  pass  down  the  modiolus,  and  thence  to  the  pons  (see  p.  676). 

Physiology  of  Hearing. 

Sounds  are  caused  by  vibrations ;  when  a  piano-string  is  struck, 
it  is  thrown  into  a  series  of  rapid  regular  vibrations ;  the  more 
rapidly  the  vibrations  occur  the  higher  is  the  pitch  of  the  musical 
note;  the  greater  the  amplitude  of  the  vibration,  the  louder  or 
more  intense  is  the  tone;  if  the  vibrations  are  regular  and  simple 
(pendular),  the  tone  is  pure ;  if  they  are  regular  but  compound,  the 
tone  is  impure,  and  its  quality  or  timbre  is  dependent  on  the  rate 
and  amplitude  of  the  simple  vibrations  of  which  the  compound 
vibrations  are  composed.  The  vibrations  are  transmitted  as  waves, 
and  ultimately  affect  the  hair-cells  at  the  extremities  of  the 
auditory  nerve  in  the  cochlea.  The  semicircular  canals  are  not 
concerned  in  the  sense  of  hearing ;  their  function  in  connection  with 
equilibration  is  described  in  Chapter  LI.  The  external  and 
middle  ears  are  conducting;  the  internal  ear  is  conducting  and 
receptive.  In  the  external  ear  the  vibrations  travel  through  air ;  in 
the  middle  ear  through  solid  structures — membranes  and  bones  ;  and 
in  the  internal  ear  through  fluid,  first  through  the  perilymph  on  the 
far  side  of  the  fenestra  ovalis ;  and  then  the  vibrations  pass  through 
the  basilar  membrane  and  membrane  of  Eeissner,  and  set  the  endo- 
lymph  of  the  canal  of  the  cochlea  in  motion. 

This  is  the  normal  way  in  which  the  vibrations  pass,  but  the  endolymph  may  be 
affected  in  other  ways,  for  instance  through  the  other  bones  of  the  head ;  one  can, 
for  example,  hear  the  ticking  of  one's  watch  when  it  is  placed  between  the  teeth, 
even  when  the  ears  are  stopped.  From  this  fact  is  derived  a  valuable  practical 
method  of  distinguishing  in  a  deaf  person  what  part  of  the  organ  of  hearing  is  at 
fault.  The  patient  may  not  be  able  to  hear  a  watch  or  a  tuning-fork  when  it  is  held 
close  to  the  ear  ;  but  if  he  can  hear  it  when  it  is  placed  between  his  teeth,  or  on  his 
forehead,  the  malady  is  localised  in  either  the  external  or  middle  ear  ;  if  he  can  hear 
it  in  neither  situation,  it  is  a  much  more  serious  case,  for  then  the  internal  ear  or  the 
nervous  mechanism  of  hearing  is  at  fault.  In  disease  of  the  middle  ear  the  hearing 
of  low  tones  is  especially  affected ;  high  tones  appear  to  be  transmissible  by  bone- 
conduction  more  readily  than  low. 


CH.  LVI.]  PHYSIOLOGY  OF  HEAKING  795 

In  connection  with  the  external  ear  there  is  not  much  more  to  be 
said ;  the  pinna  in  many  animals  is  large  and  acts  as  a  kind  of  natural 
ear-trumpet  to  collect  the  vibrations  of  the  air ;  in  man  this  function 
is  to  a  very  great  extent  lost,  and  though  there  are  muscles  present  to 
move  it  into  appropriate  postures,  they  are  not  under  the  control  of  the 
will  in  the  majority  of  people,  and  are  functionless,  ancestral  vestiges. 

In  the  middle  ear,  however,  there  are  several  points  to  be  con- 
sidered, namely,  the  action  of  the  membrana  tympani,  of  the  ossicles, 
of  the  tympanic  muscles,  and  of  the  Eustachian  tube. 

The  Membrana  Tympani. — This  membrane,  unlike  that  of 
ordinary  drums,  can  take  up  and  vibrate  in  response  to,  not  only  its 
own  fundamental  tone,  but  to  an  immense  range  of  tones  differing 
from  each  other  by  many  octaves.  This  would  clearly  be  impos- 
sible if  it  were  an  evenly  stretched  membrane.  It  is  not  evenly  nor 
very  tightly  stretched,  but  owing  to  its  attachment  to  the  chain  of 
ossicles  it  is  slightly  funnel-shaped :  the  ossicles  also  damp  the  con- 
tinuance of  the  vibrations. 

"When  the  membrane  gets  too  tightly  stretched,  by  increase  or 
decrease  of  the  pressure  of  the  air  in  the  tympanum,  then  the  sense 
of  hearing  is  dulled.  The  pressure  in  the  tympanic  cavity  is  kept 
the  same  as  that  of  the  atmosphere  by  the  Eustachian  tube,  which 
leads  from  the  cavity  to  the  pharynx,  and  so  to  the  external  air. 
The  Eustachian  tube  is  not,  however,  always  open ;  it  is  opened  by 
the  action  of  the  tensor  palati  during  swallowing.  Suppose  it  were 
closed  owing  to  swelling  of  its  mucous  membrane — this  often 
happens  in  inflammation  of  the  throat — the  result  would  be  what  is 
called  Eustachian  or  throat  deafness,  and  this  is  relieved  by  passing 
a  catheter  so  as  to  open  the  tube.  When  the  tube  is  closed,  an 
interchange  of  gases  takes  place  between  the  imprisoned  air  and  the 
blood  of  the  tympanic  vessels.  In  time,  as  in  the  aerotonometer 
(see  p.  363),  equilibrium  is  established  and  the  tension  of  the 
imprisoned  gases  becomes  equal  to  that  of  the  blood-gases,  not  to 
that  of  the  atmosphere.  The  membrane  is  therefore  cupped  inwards 
by  the  atmospheric  pressure  on  its  exterior ;  it  is  this  increased 
tightening  of  the  membrane  that  produces  deafness.  There  is  also 
an  accumulation  of  mucus.  When  one  makes  a  violent  expiration, 
as  in  sneezing,  some  air  is  often  forced  through  the  Eustachian  tube 
into  the  tympanum.  The  ears  feel  as  though  they  were  bulged  out, 
as  indeed  the  membrana  tympani  is,  and  there  is  again  partial  deaf- 
ness, which  sensations  are  at  once  relieved  by  swallowing,  so 
as  to  open  the  Eustachian  tube  and  thus  re-establish  equality  of 
pressure. 

The  ossicles  communicate  the  vibrations  of  the  membrana 
tympani  (to  which  the  handle  of  the  malleus  is  fixed)  to  the  mem- 
brane which  closes  the  fenestra  ovalis  (to  which  the  foot  of  the 


796  HEARING  [CH.  LVI. 

stapes  is  attached).  Thus  the  vibrations  are  communicated  to 
the  fluid  of  the  internal  ear,  which  is  situated  on  the  other  side  of 
the  oval  window. 

The  accompanying  diagram  will  assist  us  in  understanding  how 
this  is  brought  about.  The  bones  all  vibrate  as  if  they  were  one, 
the  slight  movements  between  the  individual  bones  being  inappreci- 
able. The  utility  of  there  being  several  bones  is  seen  when  the 
vibrations  are  excessive;  the  small  amount  of  "give"  at  the 
articulations  is  really  protective  and  tends  to  prevent  fractures. 

The  handle  of  the  malleus  is  inserted  between  the  layers  of  the 
tympanic  membrane ;  the  processus  gracilis  (p.g.)  has  its  end  A 

attached  to  the  tympanic  wall  on 
the  inner  aspect  of  the  Glaserian 
fissure ;  the  end  B  of  the  short  pro- 
cess (s.p.)  of  the  incus  is  fastened 
by  a  ligament  to  the  opposite  wall 
of  the  tympanic  cavity;  the  end 
D  of  the  long  process  of  the  incus 
articulates  with   the  stirrup,  the 
-Foot  of        base  of  which  is  turned  towards 
Stapes         the  reader.     The  handle  vibrates 
with  the  membrana  tympani ;  and 
the  vibrations  of  the  whole  chain 
C  take  place  round  the  axis  of  rota- 

FIG.  496.— Diagrammatic  view  of  ear  ossicles.         tlOU     AB.        Every    time     C     COmeS 

forwards  D  comes  forwards;  but 

by  drawing  perpendiculars  from  C  and  D  to  the  axis  of  rotation,  it  is 
found  that  I)  is  about  f  of  the  distance  from  the  axis  that  C  is.  So 
in  the  transmission  of  the  vibrations  from  membrane  to  membrane 
across  the  bony  chain,  the  amplitude  of  the  vibration  is  decreased  by 
about  J,  and  the  force  is  correspondingly  increased.  This  increase  of 
power  is  augmented  by  the  fact  that  the  tympanic  membrane  concen- 
trates its  power  upon  an  area  (the  membrane  of  the  oval  window)  only 
one-twentieth  of  its  size.  The  final  movement  of  the  stapes  is,  how- 
ever, always  very  small;  it  varies  from  ^  to  less  than  10;OQ  of  a 
millimetre. 

The  action  of  the  tensor  tympani,  by  pulling  in  the  handle  of  the 
malleus,  increases  the  tension  of  the  membrana  tympani.  It  is 
supplied  by  the  fifth  nerve.  It  is  opposed  by  the  strong  external 
ligament  of  the  malleus.  The  stapedius  attached  to  the  neck  of  the 
stapes  tilts  it  backwards  and  diminishes  the  intra-tympanic  air- 
pressure.  It  is  supplied  by  the  seventh  nerve. 

The  next  very  simple  diagram  (fig.  497)  will  explain  the  use  of 
tihefenestra  rotunda. 

The  cochlea  is  supposed  to  be  uncoiled ;  the  scala  vestibuli  leads 


CH.  LVI.]  THE  RANGE  OF  HEARING  797 

from  the  fenestra  ovalis,  to  the  other  side  of  which  the  stapes  is 
attached ;  the  scala  tympani  leads  to  the  fenestra  rotunda ;  the  two 
scalse  communicate  at  the  helicotrema,  and  are  separated  from  the 
canal  of  the  cochlea  by  the  basilar  membrane,  and  the  membrane  of 
Eeissner.  C.R  is  the  canalis  reuniens  leading  to  the  saccule.  The 
cochlea  is  filled  with  incompressible  fluid  in  an  inexpansible  bony 
case,  except  where  the  windows  are  closed  by  membranes.  Hence 
every  time  the  membrane  of  the  oval  window  is  bulged  in  by  the 
stirrup,  the  membrane  of  the  round  window  is  simultaneously  bulged 
out  to  the  same  extent,  and  vice  versd.  These  changes  of  pressure 
are  transmitted  from  one  scala  to  the  other  directly  through  the 
cochlear  canal,  setting  it  into  vibration,  and  through  the  helicotrema. 
The  range  of  hearing  extends  over  10  or  11  octaves;  the  lowest 
audible  tone  having  about  20,  the  highest  about  25,000,  vibrations 
per  second.  The  range  varies  in  different  people,  and  diminishes 
from  childhood  onwards.  The  upper  limit  of  hearing  may  be  tested 

F.Oualis 
Stapes 


Scala    Vestibuli    (Perilymph) 

'Canal    of-Qocniea     ('Endolijmph)  ^ 

Scala    Tympani    (Perilymph)  Helicotrema 


F.  Rotunda 

FIG.  497. — Diagram  to  illustrate  the  use  of  the  fenestra  rotunda. 

by  minute  tuning-forks,  metal  rods,  or  by  Galton's  whistle.  Many 
animals  appear  to  be  able  to  detect  high  tones  which  lie  beyond  the 
human  limit.  The  lower  limit  may  be  determined  by  very  large  tuning- 
forks,  or  by  employing  very  low  difference-tones. 

Difference-tones  are  produced  when  two  tones  of  different  pitch, 
m  and  n,  are  sounded  together.  A  tone  having  the  pitch  m  minus  n 
is  then  heard  in  addition  to  the  tones  m  and  n :  also  a  summation 
tone  of  pitch  m  plus  n  may  be  heard,  but  with  greater  difficulty. 
When  m  and  n  are  nearly  equal,  a  beating  tone,  instead  of  a  difference- 
tone,  results,  having  a  pitch  somewhere  intermediate  between  m  and  n. 
If  the  difference  between  m  and  n  is  exceedingly  small,  this  beating- 
tone  alone  is  heard.  The  frequency  of  the  beats  corresponds  to  the 
difference  in  vibration-rates,  m  and  n.  Under  certain  conditions  the 
difference  and  summation-tones  (which  are  collectively  called  combina- 
tion-tones) exist  in  the  air;  their  presence  being  demonstrable  by 
their  reinforcement  before  appropriate  resonators.  More  generally, 
however,  they  appear  to  be  produced  within  the  ear,  i.e.,  they  have 
merely  a  subjective  origin.  The  smallest  perceptible  difference  in 
pitch  between  two  successive  tones  is  about  0'2  vibrations  in  the 
middle  region  of  the  piano  for  trained  subjects.  Practice  effects 
extraordinary  improvement,  even  among  the  most  unmusical. 


798  HEARING  [CH.  LVI. 

There  can  be  little  doubt  that  the  cochlea  is  the  organ  specially 
concerned  in  hearing.  It  first  appears  among  vertebrata  in  certain 
fishes  as  a  very  rudimentary  structure.  If  the  cochlea  is  removed 
from  dogs,  they  become  deaf. 

There  are  two  classes  of  theories  of  hearing,  in  both  of  which  the 
basilar  membrane  of  the  cochlea  plays  the  essential  part. 

The  one  class  comprises  the  many  "sound-picture"  theories 
which  have  been  advanced  in  very  various  forms  by  Eutherford, 
Waller,  Hurst,  Ewald,  and  Meyer.  The  entire  basilar  membrane  is 
supposed  to  vibrate  either  as  a  telephone  plate,  or  as  an  elastic  mem- 
brane, different  tones  or  combinations  of  tones  giving  rise  to  different 
patterns  of  vibrations  which  are  communicated  to  the  hair-cells  and 
thence  by  the  auditory  nerve-fibres  to  the  brain,  where  (in  Euther- 
ford's  theory)  the  analysis  of  these  patterns  is  held  to  take  place. 

The  other  is  the  resonance-theory  of  Helmholtz,  in  which  the 
pitch  of  a  tone,  or  the  analysis  of  a  complex  sound  into  its  constituent 
tones,  is  determined  not  in  the  brain  but  in  the  cochlea.  It  depends 
on  the  principle  of  sympathetic  vibration.  As  is  well  known,  if  a 
tone  is  sung  in  front  of  a  piano  (best  with  the  loud  pedal  held  down), 
the  string  of  the  piano  which  is  attuned  to  that  tone  will  immediately 
respond;  another  tone  will  elicit  response  from  another  string.  So 
in  the  cochlea  the  appropriate  fibre  of  the  basilar  membrane  is  thrown 
into  vibration  when  the  tone  to  which  it  is  attuned  reaches  it.  The 
fibre  thus  stimulated  affects  the  hair-cells  above  it,  whence  the  stimulus 
is  conducted  to  the  brain.  If  two  tones  are  sounded  together,  the  two 
appropriate  fibres  respond,  and  the  analysis  of  the  now  more  complex 
stimulus  is  performed  in  the  cochlea.  The  fibres  of  the  basilar 
membrane  increase  in  length  from  the  base  towards  the  apex  of  the 
cochlea.  According  to  the  resonance-theory,  the  upper  part  of  the 
organ  would  thus  be  affected  by  low  tones,  the  lower  part  by  high 
tones. 

The  first  of  these  two  classes  of  theory  makes  it  difficult  or 
impossible  for  us  to  explain  our  ability  to  analyse  complex  chords 
into  their  component  tones.  The  full  acceptance  of  the  second  is 
difficult  in  the  face  of  the  small  difference  of  length  (at  most  1 :  12) 
between  the  shortest  and  the  longest  of  the  basilar  fibres.  On  the 
other  hand,  it  gains  support  from  the  effects  of  experiment  on,  and 
disease  of,  different  portions  of  the  cochlea.  For  instance,  the  deaf- 
ness to  high-pitched  tones  (seen  in  boiler-makers)  is  stated  to  be 
associated  with  disease  of  the  lower  whorl  of  the  cochlea. 

It  may  be  that  the  fibres  of  the  basilar  membrane  do  not 
vibrate  as  Helmholtz  supposed,  but  that  the  hair-cells  themselves 
are  each  in  some  unknown  way  specially  attuned  to  respond  only  to 
one  of  the  many  tonal  stimuli  which  may  reach  them  (Myers). 


CHAP  TEE      L  V  I  I 


VOICE  AND   SPEECH 


THE  fundamental  tones  of  the  voice  are  produced  by  the  current  of 
expired  air  causing  the  vibration  of  the  vocal  cords,  two  elastic  bands 
contained  in  a  cartilaginous  box  placed  at  the  top  of  the  windpipe 
or  trachea.  This  box  is  called  the  larynx.  The  sounds  produced 
here  are  modified  by  other  parts  such  as  the  tongue,  teeth,  and  lips, 
as  will  be  explained  later  on. 

Anatomy  of  the  Larynx. 

The  cartilages  of  the  larynx  are  the  thyroid,  the  cricoid,  and  the  two  arytenoids. 
These  are  the  most  important  for  voice  production ;  they  are  made  of  hyaline  carti- 


Cornu  min. 
Cornu  maj- ... 


Cornu  sup. 


..  m. '  Sterno-hyoideus 


-  in.  Thyro-hyoideus. 


m.  Sterno-hyoideus. 
m.  Crico-thyroideus 


Lig.  crico-thyr.  nied. 

Cart,  cricoidea 
Lig.  crico-trachese 

Cart,  tracheale 


FIG.  498. — The  larynx,  as  seen  from  the  front,  showing  the  cartilages  and  ligaments.  The  muscles,  with 
the  exception  of  one  crico-thyroid,  are  cut  off  short.    (Stoerk.) 

lage.     Then  there  are  the  epiglottis,  two  cornicular,  and  two  cuneiform  cartilages. 
These  are  made  of  yellow  fibre-cartilage. 

The  thyroid  cartilage  (fig.  499, 1  to  4)  does  not  form  a  complete  ring  around  the 
larynx,  but  only  covers  the  front  portion.     It  forms  the  prominence  in  front  of  the 

799 


800 


VOICE   AND    SPEECH 


[CH.  LYII. 


throat  known  as  Adam's  apple.  The  cricoid  cartilage  (fig.  499,  5,  6),  on  the  other 
hand,  is  a  complete  ring ;  the  back  part  of  the  ring  is  much  broader  than  the  front. 
On  the  top  of  this  broad  portion  of  the  cricoid  are  the  arytenoid  cartilages  (fig. 
499,  7) ;  the  connections  between  the  cricoid  below  and  arytenoid  cartilages  above 
are  joints  with  synovial  membrane  and  ligaments,  the  latter  permitting  tolerably 


FIG.  499. — Cartilages  of  the  larynx  seen  from  the  front.  1  to  4,  Thyroid  cartilage  ;  1,  vertical  ridge  or 
pomum  Adami ;  2,  right  ala ;  3,  superior,  and  4,  inferior  cornu  of  the  right  side  ;  5,  6,  cricoid  carti- 
lage ;  5,  inside  of  the  posterior  part ;  6,  anterior  narrow  part  of  the  ring ;  7,  arytenoid  cartilages,  x  f . 

free  motion  between  them.  But  although  the  arytenoid  cartilages  can  move  on  the 
cricoid,  they  accompany  the  latter  in  all  its  movements.  The  base  by  means  of 
which  each  arytenoid  cartilage  sits  on  the  cricoid  is  triangular  ;  the  anterior  angle  is 
often  called  the  vocal  process  :  to  it  the  posterior  ends  of  the  true  vocal  cords  are 
attached.  The  outer  angle  is  thick,  and  called  the  muscular  process. 

The  cornicular  cartilages,  or  cartilages  of  Santorini,  are  perched  on  the  top  of 


Lig.  ary-epiglott. 


Cart.  Wrisbergii. 
Cart.  Santorini. 

Cart,  aryten. 
Proc.  muscul. 

Lig.  crico-aryten. 
Lig.  cerato-crico.  post.  sup. 

Cornu  infer. 
Lig.  cerato-crico.  post.  inf. 


Cart,  tracheae.  <-' 


Pars  membran. 


FIG.  500. — The  larynx  as  seen  from  behind  after  removal  of  the  muscles.     The  cartilages  and  ligaments 

only  remain.    (Stoerk.) 

the  arytenoids  ;  the  cuneiform  cartilages,  or  cartilages  of  Wrisberg,  are  in  a  fold  of 
mucous  membrane  ;  the  epiglottis  looks  like  a  lid  to  the  whole  (fig.  500). 

The  thyroid  cartilage  is  connected  with  the  cricoid,  by  the  crico-thyroid  mem- 
brane, and  also  by  joints  with  synovial  membranes  ;  the  lower  cornua  of  the  thyroid 
clasp  the  cricoid  between  them,  yet  not  so  tightly  but  that  the  thyroid  can  revolve, 
within  a  certain  range,  around  an  axis  passing  transversely  through  the  two  joints 


CH.  LVIL] 


THE   LARYNX 


801 


at  which  the  cricoid  is  clasped.  The  vocal  cords  are  attached  behind  to  the  front 
portion  of  the  base  (vocal  process)  of  the  arytenoid  cartilages,  and  in  front  to  the 
re-entering  angle  at  the  back  of  the  thyroid  ;  it  is  evident,  therefore,  that  all  move- 
ments of  either  of  these  cartilages  must  produce  an  effect  on  them  of  some  kind  or 
other.  Inasmuch,  too,  as  the  arytenoid  cartilages  rest  on  the  top  of  the  back  portion 
of  the  cricoid  cartilage,  and  are  connected  with  it  by  capsular  and  other  ligaments, 
all  movements  of  the  cricoid  cartilage  must  move  the  arytenoid  cartilages,  and  also 
produce  an  effect  on  the  vocal  cords. 

Mucous  membrane. — The  larynx  is  lined  with  a  mucous  membrane  continuous 
with  that  of  the  trachea ;  this  is  covered  with  ciliated  epithelium  except  over  the  vocal 
cords  and  epiglottis,  where  it  is 
stratified.  The  vocal  cords  are 
thickened  bands  of  elastic  tissue  in 
this  mucous  membrane  which  run 
from  before  back.  They  are  at- 
tached behind  to  the  vocal  processes 
of  the  arytenoid  cartilages,  and  in 
front  to  the  angle  where  the  two 
wings  of  the  thyroid  meet.  The 
chink  between  them  is  called  the 
rima  glottidis  (see  fig.  501).  Two 
ridges  of  mucous  membrane  above 
and  parallel  to  these  are  called  the 
false  vocal  cords;  between  the  true 
and  false  vocal  cord  on  each  side  is 
a  recess  called  the  ventricle. 

Muscles. — The  muscles  of  the 
larynx  are  divided  into  intrinsic  and 
extrinsic.  The  intrinsic  are  named 
from  their  attachments  to  the  various 
cartilages ;  the  extrinsic  are  those 
which  connect  the  larynx  to  other 
parts,  such  as  the  hyoid  bone. 

The  intrinsic  muscles  of  the 
larynx  are  as  follows: — 

1.  Crico-thyroid. 

2.  Posterior  crico-arytenoid. 

3.  Lateral  crico-arytenoid. 

4.  Thyro-arytenoid. 

5.  Arytenoid. 

All  these  muscles  except  the 
arytenoid  are  in  pairs. 

Their  attachments  and  actions 
are  as  follows  :— 


F.V.C, 


T.A. 


T.C.M. 


FIG.  501.— Vertical  section  through  the  larynx,  passing 
from  side  to  side.  H,  hyoid  bone ;  T.,  thyroid  carti- 
lage ;  T.C.M.,  thyro-cricoid  membrane  ;  C.,  cricoid 
cartilage;  Tr.,  first  ring  of  trachea;  T.A.,  thyro- 
arytenoid muscle  ;  R.G.,  rima  glottidis;  V.C.,  vocal 
cord ;  V. ,  ventricle ;  F. V.C. ,  false  vocal  cord.  (After 
Allen  Thomson.) 


1.  Crico-  thyroid. — This    is    a 
short,  thick  triangular  muscle,   at- 
tached below  to  the  cricoid  cartilage ; 

this  attachment  extends  from  the  middle  line  backwards.  The  fibres  pass  upwards 
and  outwards,  diverging  slightly  to  be  attached  above  to  the  inferior  border  of  the 
thyroid  cartilage,  and  to  the  anterior  border  of  its  lower  cornu. 

The  thyroid  cartilage  being  fixed  by  extrinsic  muscles,  the  contraction  of  this 
muscle  draws  upwards  the  anterior  part  of  the  cricoid  cartilage,  and  depresses  the 
posterior  part,  and  with  it  the  arytenoid  cartilages,  so  that  the  vocal  cords  are 
stretched.  Paralysis  of  these  muscles  therefore  causes  an  inability  to  produce  high- 
pitched  tones. 

2.  Posterior  crico-arytenoid. — This   arises   from  the  broad   depression  on  the 
corresponding  half  of  the  posterior  surface  of  the  cricoid  cartilage ;  its  fibres  con- 
verge upwards  and  outwards,  and  are  inserted  into  the  outer  angle  of  the  base  of  the 
arytenoid  cartilage  behind  the  attachment  of  the  lateral  crico-arytenoid  muscle. 

These  muscles  draw  the  outer  angles  of  the  arytenoid  cartilages  backwards  and 

3E 


802 


VOICE   AND   SPEECH 


[CH.  LVII. 


inwards,  and  thus  rotate  the  anterior  or  vocal  processes  outwards,  and  widen  the 
rima  glottidis.  They  come  into  action  during  deep  inspiration.  If  they  are  paralysed, 
the  lips  of  the  glottis  approach  the  middle  line  and  come  in  contact  during  each 
inspiration,  so  that  dyspnoea  is  produced. 

3.  Lateral  crico-arytenoid. — This  arises  from  the  sloping  upper  border  of  the 
cricoid  cartilage,  and  is  inserted  into  the  muscular  process  of  the  arytenoid  carti- 
lage, and  the  adjacent  part  of  its  anterior  surface. 

These  muscles  draw  the  muscular  processes  of  the  arytenoid  cartilages  forwards 

and  downwards,  and  thus  ap- 
proximate the  vocal  cords.  They 
are  antagonistic  to  the  posterior 
crico-arytenoids. 

4.  Thyro  -  arytenoid.  —  This 
consists  of  two  portions,  inner 
and  outer.  The  inner  portion 
arises  in  the  lower  half  of  the 
angle  formed  by  the  alae  of  the 
thyroid  cartilage,  and  passing 
backwards  is  attached  behind  to 
the  vocal  process  and  to  the  ad- 
jacent parts  of  the  outer  surface 
of  the  arytenoid  cartilage.  These 
fibres  are  joined  internally  by 
short  fibres  which  are  attached 
in  front  to  the  vocal  cord,  and 
behind  to  the  vocal  process. 
Some  oblique  fibres  pass  from 
the  sloping  portion  of  the  crico- 
thyroid  membrane  below  the 
vocal  cord,  upwards,  outwards, 
and  somewhat  backwards,  to 
end  in  the  tissue  of  the  false 
vocal  cord.  The  fibres  of  the 
outer  portion  arise  in  front  from 
the  thyroid  cartilage  close  to  the 
origin  of  the  inner  portion  and  from  the  crico-thyroid  membrane.  They  pass  back- 
wards to  be  inserted  in  part  into  the  lateral  border  and  muscular  process  of  the 
arytenoid  cartilage,  and  in  part  they  pass  obliquely  upwards  towards  the  aryteno- 
epiglottidean  fold,  ending  in  the  false  vocal  cord.  The  portion  of  this  muscle  which 
extends  towards  the  epiglottis  is  often  described  as  a  separate  muscle  (thyro- 
epiglottidean) ;  it  resembles  the  crico-arytenoid  in  that  some  of  its  fibres  are  con- 
tinuous with  those  of  the  arytenoid  muscle. 

The  antero-posterior  fibres  will  tend  to  draw  forward  the  arytenoid  cartilage, 
and  with  it  the  posterior  part  of  the  cricoid  cartilage,  rotating  the  latter  upwards 
and  antagonising  the  action  of  the  crico-thyroid  muscle,  the  effect  being  to  relax  the 
vocal  cords.  But  if  the  latter  are  kept  stretched  those  fibres  of  the  inner  portion  of 
the  muscle  which  are  inserted  into  the  vocal  cord  may  serve  to  modify  its  elasticity, 
tightening  the  parts  of  the  cord  in  front  of,  and  relaxing  those  behind,  its  attach- 
ment. The  vertical  fibres  of  the  muscle  which  extend  from  the  crico-thyroid  mem- 
brane across  the  base  of  the  vocal  fold  and  over  the  ventricle  into  the  false  vocal 
cord,  render  the  free  edge  of  the  former  more  prominent.  Then  the  fibres  which  are 
inserted  into  the  muscular  process  and  outer  surface  of  the  arytenoid  cartilage  will 
tend  to  draw  the  arytenoid  cartilage  forwards  and  rotate  it  inwards  ;  finally,  the  fibres 
which  pass  into  the  aryteno-epiglottidean  fold  may  assist  in  depressing  the  epiglottis. 
If  these  muscles  are  paralysed,  the  lips  of  the  glottis  are  no  longer  parallel,  but 
are  curved  with  the  concavity  inwards,  and  a  much  stronger  blast  of  air  is  required 
for  the  production  of  the  voice. 

5.  Arytenoid. — When  the  mucous  membrane  is  removed  from  the  back  of  the 
arytenoid  cartilages,  a  band  of  transverse  fibres  is  exposed,  on  the  dorsal  surface  of 
which  are  two  slender  decussating  oblique  bundles.  These  are  often  described  as 


Lig.  ary-epiglott. 

Cart.  Wrisbergii  •£-• 
Cart.  Santorini 

mm  Aryten.  obliqu. 

Crico-arytenoid.  post. 

Cornu  inferior 

Lig.  cerato-cric. 

Pars  post.  inf.  membrani 

Pars  cartilag 


FIG.  502. — The  larynx  as  seen  from  behind.    To  show  the 
intrinsic  muscles  posteriorly.    (Stoerk.) 


CH.  LVIL] 


THE   LARYNGOSCOPE 


803 


separate  muscles  (arytenoid  and  aryteno-epiglottidean),  but  they  are  intimately 
blended  together.  The  ventral  fibres  (arytenoid  proper)  pass  straight  across  from 
the  outer  half  of  the  concave  surface  on  the  back  of  one  arytenoid  cartilage  to  the 
corresponding  surface  of  the  other.  The  dorsal  fibres  can  be  followed  to  the  lateral 
walls  of  the  larynx,  the  uppermost  ones  to  the  cartilage  of  Santorini,  the  intermediate 
ones  run  with  the  uppermost  fibres  of  the  thyro-arytenoid  muscle  forming  the  so- 
called  aryteno-epiglottidean  muscle,  and  the  lowest  fibres  blend  at  the  level  of  the 
true  vocal  cords  with  the  thyro-arytenoid  and  lateral  crico-arytenoid  muscles. 

The  arytenoid  muscle  draws  the  arytenoid  cartilages  together.  If  it  is  paralysed, 
the  intercartilaginous  part  of  the  glottis  remains  open,  although  the  membranous  lips 
can  still  be  approximated  during  vocalisation. 

It  has  been  generally  supposed  that  the  epiglottis  is  depressed  as  a  lid  over  the 
glottis  during  swallowing.  This  may  be  so  in  some  animals,  but  in  man  it  is  not 
the  case ;  the  epiglottis  projects  upwards  in  close  contact  with  the  base  of  the  tongue. 
The  necessary  closure  of  the  glottis  during  swallowing  is  brought  about  by  the  con- 
traction of  the  arytenoid  and  thyro-arytenoid  muscles  ;  by  this  means  the  arytenoid 
cartilages  are  drawn  towards  each  other,  and  also  forwards  into  contact  with  the 
posterior  surface  of  the  epiglottis  (Anderson  Stuart).  Henle  remarked  that  "the 
muscles  which  lie  in  the  space  enclosed  by  the  laminae  of  the  thyroid  cartilage  and 
above  the  cricoid  may  be  regarded  in  their  totality  as  a  kind  of  sphincter  such  as  is 
found  in  its  simplest  form  embracing  the  entrance  of  the  larynx  in  reptiles  "  (Quain's 
Anatomy). 

Nerves. — The  larynx  is  supplied  by  two  branches  of  the  vagus ;  the  superior 
larynyeal  is  the  sensory  nerve ;  by  its  external  branch,  it  supplies  one  muscle,  namely, 
the  crico-thyroid.  These  fibres,  however,  probably  arise  from  glosso-pharyngeal  root- 
lets. The  rest  of  the  muscles  are  supplied  by  the  inferior  laryngeal  nerve,  the 
fibres  of  which  come  from  the  spinal  accessory,  not  the  vagus  proper. 

The  laryngoscope  is  an  instrument  employed  in  investigating  during  life  the 
condition  of  the  pharynx,  larynx,  and  trachea.  It  consists  of  a  large  concave  mirror 


FIG.  503  —To  show  the  position  of  the  operator  and  patient  when  using  the  Laryngoscope. 


with  perforated  centre,  and  of  a  smaller  mirror  fixed  in  a  long  handle.  The  patient 
is  placed  in  a  chair,  a  good  light  (argand  burner,  or  electric  lamp)  is  arranged  on  one 
side  of,  and  a  little  above,  his  head.  The  operator  fixes  the  large  mirror  round  his 
head  in  such  a  manner,  that  he  looks  through  the  central  aperture  with  one  eye. 
He  then  seats  himself  opposite  the  patient,  and  so  alters  the  position  of  the  mirror, 
which  is  for  this  purpose  provided  with  a  ball-and-socket  joint,  that  a  beam  of  light 
is  reflected  on  the  lips  of  the  patient. 

The  patient  is  now  directed  to  throw  his  head  slightly  backwards,  and  to  open  his 
mouth ;  the  reflection  from  the  mirror  lights  up  the  cavity  of  the  mouth,  and  by  a 


804  VOICE  AND   SPEECH  [CH.  LV1I. 

little  alteration  of  the  distance  between  the  operator  and  the  patient  the  point  at 
which  the  greatest  amount  of  light  is  reflected  by  the  mirror — in  other  words,  its 
focal  length — is  readily  discovered.  The  small  mirror  fixed  in  the  handle  is  then 
warmed,  either  by  holding  it  over  the  lamp,  or  by  putting  it  into  a  vessel  of  warm 
water;  this  is  necessary  to  prevent  the  condensation  of  breath  upon  its  surface. 
The  degree  of  heat  is  regulated  by  applying  the  back  of  the  mirror  to  the  hand  or 
cheek,  when  it  should  feel  warm  without  being  painful. 

After  these  preliminaries  the  patient  is  directed  to  put  out  his  tongue,  which  is 
held  by  the  left  hand  gently  but  firmly  against  the  lower  teeth  by  means  of  a 
handkerchief.  The  warm  mirror  is  passed  to  the  back  of  the  mouth,  until  it  rests 
upon  and  slightly  raises  the  base  of  the  uvula,  and  at  the  same  time  the  light  is 
directed  upon  it :  an  inverted  image  of  the  larynx  and  trachea  will  be  seen  in  the 
mirror.  If  the  dorsum  of  the  tongue  is  alone  seen,  the  handle  of  the  mirror  must 
be  slightly  lowered  until  the  larynx  comes  into  view ;  care  should  be  taken,  how- 
ever, not  to  move  the  mirror  upon  the  uvula,  as  it  excites  retching.  The  observa- 
tion should  not  be  prolonged,  but  should  rather  be  repeated  at  short  intervals. 

The  structures  seen  will  vary  somewhat  according  to  the  condition  of  the  parts 
as  to  inspiration,  expiration,  phonation,  etc.  ;  they  are  (fig.  504)  first,  and  apparently 
at  the  posterior  part,  the  base  of  the  tongue,  immediately  below  which  is  the  arcuate 
outline  of  the  epiglottis,  with  its  cushion  or  tubercle.  Then  are  seen  in  the  central 
line  the  true  vocal  cords,  white  and  shining  in  their  normal  condition.  The  cords 
approximate  (in  the  inverted  image)  posteriorly;  between  them  is  left  a  chink, 
narrow  whilst  a  high  note  is  being  sung,  wide  during  a  deep  inspiration.  On  each 
side  of  the  true  vocal  cords,  and  on  a  higher  level,  are  the  pink,  false  vocal  cords. 
Still  more  externally  than  the  false  vocal  cords  is  the  aryteno-epiglottidean  fold,  in 
which  are  situated  upon  each  side  three  small  elevations  ;  of  these  the  most  external 
is  the  cartilage  of  Wrisberg,  the  intermediate  is  the  cartilage  of  Santorini,  whilst 
the  summit  of  the  arytenoid  cartilage  is  in  front,  and  somewhat  below  the  preceding, 
being  only  seen  during  deep  inspiration.  The  rings  of  the  trachea,  and  even  the 
bifurcation  of  the  trachea  itself,  if  the  patient  be  directed  to  draw  a  deep  breath, 
may  be  seen  in  the  interval  between  the  true  vocal  cords. 

Movements  of  the  Vocal  Cords. 

In  Respiration. — The  position  of  the  vocal  cords  in  ordinary 
tranquil  breathing  is  so  adapted  by  the  muscles,  that  the  opening 
of  the  glottis  is  wide  and  triangular  (fig.  504,  B).  The  glottis 
remains  unaltered  during  ordinary  quiet  breathing,  though  in  a 
small  proportion  of  people  it  becomes  a  little  wider  at  each  inspira- 
tion, and  a  little  narrower  at  each  expiration.  In  the  cadaveric 
position  the  glottis  has  about  half  the  width  it  has  during  ordi- 
nary breathing;  during  life,  therefore,  except  during  vocalisation, 
the  abductors  of  the  vocal  cords  (posterior  crico-arytenoids)  are  in 
constant  action.  (F.  Semon.)  On  making  a  rapid  and  deep  inspira- 
tion the  opening  is  widely  dilated  (fig.  504,  c),  and  somewhat 
lozenge-shaped. 

In  Vocalisation. — At  the  moment  of  the  emission  of  a  note,  the 
chink  is  narrowed,  the  margins  of  the  arytenoid  cartilages  being 
brought  into  contact,  and  the  edges  of  the  vocal  cords  approximated 
and  made  parallel  (fig.  504,  A);  at  the  same  time  their  tension  is 
much  increased.  The  higher  the  note  produced,  the  tenser  do  the 
cords  become;  and  the  range  of  a  voice  depends,  in  the  main,  on 
the  extent  to  which  the  degree  of  tension  of  the  vocal  cords  can 


CH.  LVII.] 


MOVEMENTS   OF  THE  VOCAL  CORDS 


805 


be  thus  altered.     In  the  production  of  a  high  note  the  vocal  cords 
are  brought  well  within  sight.    In  the  utterance  of  low-pitched  tones, 


Fio.  504. — Three  laryngoscopic  views  of  the  superior  aperture  of  the  larynx  and  surrounding  parts.  A, 
the  glottis  during  the  emission  of  a  high  note  in  singing ;  B,  in  easy  and  quiet  inhalation  of  air  ;  C, 
in  the  state  of  widest  possible  dilatation,  as  in  inhaling  a  very  deep  breath.  The  diagrams  A',  B',  and 
C',  show  in  horizontal  sections  of  the  glottis  the  position  of  the  vocal  cords  and  arytenoid  cartilages 
in  the  three  several  states  represented  in  the  other  figures.  In  all  the  ligures  so  far  as  marked,  the 
letters  indicate  the  parts  as  follows,  viz. :  I,  the  base  of  the  tongue  ;  e,  the  upper  free  part  of  the 
epiglottis ;  e't  the  tubercle  or  cushion  of  the  epiglottis ;  ph,  part  of  the  anterior  wall  of  the 
pharynx  behind  the  larynx ;  in  the  margin  of  the  aryteno-epiglottidean  fold,  u>,  the  swelling  of  the 
membrane  caused  by  the  cartilages  of  Wrisberg ;  s,  that  of  the  cartilages  of  Santorini ;  a,  the  tip  or 
summit  of  the  arytenoid  cartilages  ;  c  v,  the  true  vocal  cords  or  lips  of  the  rima  glottidis ;  c  v  s,  the 
superior  or  false  vocal  cords  ;  between  them  the  ventricle  of  the  larynx ;  in  C,  tr  is  placed  on  the 
anterior  wall  of  the  receding  trachea,  and  b  indicates  the  commencement  of  the  two  bronchi  beyond 
the  bifurcation  which  may  be  brought  into  view  in  this  state  of  extreme  dilatation.  (Quain,  after 
Czermak.) 

on  the  other  hand,  the  epiglottis  is  depressed  and  brought  over  them, 
and  the  arytenoid  cartilages  look  as  if  they  were  trying  to  hide  them- 
selves under  it  (fig.  505). 

The  approximation  of  the  vocal  cords  also  usually  corresponds 
with  the  height  of  the  note  produced ;  but  the  width  of  the  aperture 
has  no  influence  on  the  pitch  of  the  note,  as  long  as  the  vocal 
cords  have  the  same  tension:  only  with  a  wide  aperture  the  tone 
is  more  difficult  to  produce  and  is  less  perfect,  the  rushing  of  the 
air  through  the  aperture  being  heard  at  the  same  time. 


806  VOICE  AND   SPEECH  [CH.  LVII. 

No  true  vocal  sound  is  produced  at  the  posterior  part  of  the 
aperture  of  the  glottis,  namely,  that  which  is  formed  by  the  space 
between  the  arytenoid  cartilages. 

8  The  Voice. 

The  human  musical  instrument  is 
often  compared  to  a  reed  organ-pipe : 
certainly  the  notes  produced  by  such 
pipes  in  the  vox  humana  stop  of  organs 
is  very  like  the  human  voice.  Here 
FIG.  505.— view  of  the  upper  part  of  the  there  is  not  only  the  vibration  of  a 

larynx  as  seen  by  means  of  the  laryngo-       pnlnm-n   nf  m'r    Vmf  alan  nf   a   TAPP!     whinh 
scope  during  the  utterance  of  a  bass      COiUmn  01  air,  DUE  aiSO  01   a  reCQ,  WHICH 

note,  e,  Epiglottis ;  s,  tubercles  of  the    corresponds  to  the  vocal  cords  in  the 

cartilages  of  Santonni;  a,  arytenoid  .   r     .  ,         _     ,.  . 

cartilages;  z,  base  of  the  tongue;    air-chamber   composed   of  the   trachea 
ft^g****™*  <*"»&*****'    and  the   bronchial  system   beneath  it. 

The  pharynx,  mouth,  and  nasal  cavities 

above  the  glottis  are  resonating  cavities,  which,  by  alterations 
in  their  shape  and  size,  are  able  to  pick  out  and  emphasize 
certain  component  parts  of  the  fundamental  tones  produced  in  the 
larynx.  The  natural  voice  is  often  called  the  chest  voice.  The 
falsetto  voice  is  differently  explained  by  different  observers;  on 
laryngoscopic  examination,  the  glottis  is  found  to  be  widely  open,  so 
that  there  is  an  absence  of  chest  resonance ;  some  have  supposed 
that  the  attachment  of  the  thyro-arytenoid  muscle  to  the  vocal  cord 
renders  it  capable  of  acting  like  the  finger  on  a  violin  string, 
part  of  the  cord  being  allowed  to  vibrate  while  the  rest  is  held  still. 
Such  a  shortening  of  a  vibrating  string  would  produce  a  higher  note 
than  is  natural. 

Musical  sounds  differ  from  one  another  in  three  ways  : — 

1.  In  pitch. — This  depends  on  the  rate  of  vibration ;  and  in  the 
case  of  a  string,  the  pitch  increases  with  the  tension,  and  diminishes 
with  the  length  of  the  string.    The  vocal  cords  of  a  woman  are  shorter 
than  those  of  a  man,  hence  the  higher  pitched  voice  of  women.     The 
average  length  of  the  female  cord  is  11 '5  millimetres;  this  can  be 
stretched  to  14;  the  male  cord  averages  15*5,  and  can  be  stretched 
to  19*5  millimetres. 

2.  In  loudness. — This  depends  on  the  amplitude  of  the  vibrations, 
and  is  increased  by  the  force  of  the  expiratory  blast  which  sets  the 
cords  in  motion. 

3.  In  "  timbre." — This  is  the  difference  of  character  which  dis- 
tinguishes one  voice,  or  one  musical  instrument,  from  another.     It 
is  due  to  admixture  of  the  primary  vibrations  with  secondary  vibra- 
tions or  overtones.     If  one  takes  a    tracing  of  a  tuning-fork  on  a 
revolving  cylinder,  it  writes  a  simple  series  of  up  and  down  waves 
corresponding  in  rate  to  the  note  of  the  fork.     Other  musical  instru- 


CH.  LVIL] 


THE   VOICE   AND   SPEECH 


807 


ments  do  not  loud  themselves  to  this  form  of  graphic  record,  but  their 
vibrations  can  be  rendered  visible  by  allowing  them  to  act  on  a  small 
sensitive  gas-flame ;  this  bobs  up  and  down,  and  if  the  reflection  of 
this  flame  is  allowed  to  fall  on  a  series  of  mirrors,  the  top  of  the  con- 
tinuous image  formed  is  seen  to  present  waves.  The  mirrors  are 
usually  arranged  on  the  four  lateral  sides  of  a  cube  which  is  rapidly 
rotated  (fig.  506).  If  one  sings  a  note  on  to  the  membrane  in  the 
side  of  the  gas-chamber  with  which  the  flame  is  in  connection,  the 
waves  seen  are  not  simple  up  and  down  ones,  but  the  primary  large 
waves  are  complicated  by  smaller  ones  on  their  surface,  at  twice, 


FIG.  506.— Kouig's  apparatus  for  ob.ainmg  flame  pictures  of  musical  notes. 

thrice,  etc.,  the  rate  of  the  primary  vibration.  The  richer  a  voice, 
the  richer  the  sound  of  a  musical  instrument,  the  more  numerous 
are  these  overtones  or  harmonics.  The  range  of  the  voice  is 
seldom,  except  in  celebrated  singers,  more  than  two-and-a-half 
octaves,  and  for  different  voices  this  is  in  different  parts  of  the 
musical  scale. 

Speech. 

Speech  is  due  to  the  modification  produced  in  the  fundamental 
laryngeal  notes,  by  the  resonating  cavities  above  the  vocal  cords. 
By  modifying  the  size  and  shape  of  the  pharynx,  mouth,  and  nose, 
certain  overtones  or  harmonics  are  picked  out  and  exaggerated :  this 
gives  us  the  vowel  sounds ;  the  consonants  are  produced  by  inter- 
ruptions, more  or  less  complete,  of  the  outflowing  air  in  different 
situations.  When  the  larynx  is  passive,  and  the  resonating  cavities 
alone  come  into  play,  then  we  get  whispering. 


808  VOICE   AND   SPEECH  [CH.  LVII. 

The  pitch  of  the  Vowels  has  been  estimated  musically ;  u  has  the  lowest  pitch, 
then  o,  a  (as  in  father),  a  (as  in  cane),  «,  and  e.  We  may  give  a  few  examples  of 
the  shape  of  the  resonating  cavities  in  pronouncing  vowel  sounds,  and  producing 
their  characteristic  timbre  :  when  sounding  a  (in  father)  the  mouth  has  the  shape  of 
a  funnel  wide  in  front ;  the  tongue  lies  on  the  floor  of  the  mouth  ;  the  lips  are  wide 
open  ;  the  soft  palate  is  moderately  and  the  larynx  slightly  raised. 

In  pronouncing  u  (oo),  the  cavity  of  the  mouth  is  shaped  like  a  capacious  flask 
with  a  short  narrow  neck.  The  whole  resonating  cavity  is  then  longest,  the  lips 
being  protruded  as  far  as  possible ;  the  larynx  is  depressed  and  the  root  of  the  tongue 
approaches  the  fauces. 

In  pronouncing  o,  the  neck  of  the  flask  is  shorter  and  wider,  the  lips  being 
nearer  the  teeth  ;  the  larynx  is  slightly  higher  than  in  sounding  oo. 

In  pronouncing  e,  the  flask  is  a  small  one  with  a  long  narrow  neck.  The 
resonating  chamber  is  then  shortest  as  the  larynx  is  raised  as  much  as  possible,  and 
the  mouth  is  bounded  by  the  teeth,  the  lips  being  retracted ;  the  approach  of  the 
tongue  near  the  hard  palate  makes  the  long  neck  of  the  flask. 

The  Consonants  are  produced  by  a  more  or  less  complete  closure  of  certain 
doors  on  the  course  of  the  outgoing  blast.  If  the  closure  is  complete,  and  the  blast 
suddenly  opens  the  door,  the  result  is  an  explosive  ;  if  the  door  is  partly  closed,  and 
the  air  rushes  with  a  hiss  through  it,  the  result  is  an  aspirate  ;  if  the  door  is  nearly 
closed  and  its  margins  are  thrown  into  vibration,  the  result  is  a  vibrative ;  if  the 
mouth  is  closed,  and  the  sound  has  to  find  its  way  out  through  the  nose,  the  result 
is  a  resonant. 

These  doors  are  four  in  number  ;  Briicke  called  them  the  articulation  positions. 
They  are— 

1.  Between  the  lips. 

2.  Between  the  tongue  and  hard  palate. 

3.  Between  the  tongue  and  soft  palate. 

4.  Between  the  vocal  cords. 

The  following  table  classifies  the  principal  consonants  according  to  this 
plan : — 

Articulation 
position. 
1 
2 
3 
4 

The  introduction  of  the  phonograph  has  furnished  us  with  an  instrument  which 
it  is  hoped  in  the  future  will  enable  us  to  state  more  accurately  than  has  hitherto 
been  possible,  the  meaning  of  the  changes  in  nature  and  intensity  of  the  complex 
vibrations  which  constitute  speech.  The  microscopic  study  of  the  tracing  on  the 
recording  phonographic  cylinder,  and  various  methods  of  obtaining  a  high  magnifi- 
cation of  the  movements  of  the  recording  style  have  been  carried  out  by  M'Kendrick 
and  others.  The  subject  is,  however,  not  yet  sufficiently  ripe  for  definite  statements 
to  be  made. 

Defects  of  Speech. 

Speech  may  be  absent  in  certain  forms  of  lunacy,  and  temporarily  in  that  defect 
of  will  called  hysteria. 

It  may  be  absent  owing  to  congenital  defects.  Children  born  deaf  are  dumb 
also.  This  is  because  we  think  with  remembered  sounds,  and  in  a  person  born  deaf 
the  auditory  centres  are  never  set  into  activity.  By  educating  the  child  by  the 
visual  inlet,  it  can  be  taught  to  think  with  the  remembered  shapes  of  the  mouth 
and  expressions  of  the  face  produced  in  the  act  of  speaking,  and  so  can  itself  speak 
in  time. 

If  a  child  becomes  deaf  before  it  is  six  or  seven  years  old,  there  is  a  liability  it 
will  forget  the  speech  it  has  learnt,  and  so  become  dumb. 

In  congenital  hemiplegia  there  may  be  speechlessness,  especially  if  the  injury  is 


Explosives. 

B,P. 
T,  D. 
K,  G. 

Aspirates. 

F,  V,  W. 
S,  Z,  L,  Sch,  Th. 
J,  Ch. 
H. 

Vibratives. 

R. 
Palatal  R. 
R  of  lower  Saxon 

Resonant  s. 

M. 

N. 
Ng. 

CH.  LYII.]  DEFECTS   OF   SPEECH  809 

due  to  meningeal  haemorrhage  affecting  the  grey  cortex  of  the  left  hemisphere. 
These  children  generally  talk  late,  the  right  side  of  the  brain  taking  on  the  function 
of  the  left. 

Disorders  of  speech  and  voice  occur  from  affections  of  the  larynx,  and  of  the 
nerves  which  supply  the  larynx.  Stammering  is  a  want  of  coordination  between 
the  various  muscles  employed  in  the  act  of  speaking. 

Perhaps  the  most  interesting  of  the  disorders  of  speech,  however,  are 
those  associated  with  brain  disease  in  adults,  and  to  which  the  general 
term  Aphasia  is  given.  There  may  be  an  entire  loss  of  the  power  to 
articulate  words,  or  there  may  be  a  mere  blurring  of  the  speech.  In  other  cases 
there  is  a  loss  of  memory  for  words,  the  words  spoken  being  well  pronounced,  but 
are  not  those  which  the  patient  wishes  to  utter.  This  is  often  associated  with 
Agraphia,  a  similar  condition  in  respect  to  writing.  Some  writers  distinguish 
between  motor  aphasia,  which  is  associated  with  disorganisation  of  the  motor 
word-centre  (Broca's  convolution),  and  sensory  aphasia,  in  which  the  defect  is  in  the 
association  of  ideas  of  things  and  the  ideas  of  their  names.  This  is  due  to  injury 
of  the  visual  word-centre,  or  the  auditory  word-centre  (see  p.  741),  or  to  a  severance 
of  the  tracts  which  unite  them  to  one  another  and  to  the  motor  word-centre.  It 
will  readily  be  understood  that  the  actual  symptoms  will  vary  greatly  according  to 
the  position  of  the  lesion.  It  is  generally  admitted  that  injuries  to  the  sensory 
word-centres  are  more  potent  in  the  production  of  aphasia  than  injuries  to  Broca's 
convolution.  Marie,  as  already  noted  on  p,  734,  has  gone  so  far  as  to  assert  that  a 
lesion  limited  to  Broca's  convolution  will  not  produce  aphasia,  but  this  view  has  not 
yet  been  fully  verified. 

With  regard  to  the  auditory  word-centre,  impressions  for  the  sounds  of  words 
are  revived  in  one  of  three  ways  : — 

a.  Spontaneous  or  volitional ;  owing  to  accumulated  traces  which  constitute 
memory,  a  man  when  he  wants  to  express  his  thoughts  in  words  remembers  the 
sounds  it  is  necessary  to  use ;  impulses  pass  to  the  motor-centre  (Broca's  convolu- 
tion), thence  to  the  nerve-centres,  nerves,  and  muscles  of  the  larynx,  mouth,  chest, 
etc. ,  and  the  man  speaks. 

/>.  In  slight  disease  of  the  auditory  word-centre,  he  is  unable  to  do  this,  but  if 
his  mind  is  set  into  a  certain  groove  he  will  speak  ;  thus  if  the  alphabet  or  a  well- 
known  piece  of  poetry  be  started  for  him  he  will  finish  it  by  himself. 

<?.  Mimetic.  In  more  severe  cases,  a  more  powerful  stimulus  still  is  needed ;  he 
will  repeat  any  words  after  another  person,  but  forget  them  immediately  afterwards. 

With  regard  to  the  visual  word-centre  as  tested  by  writing,  there  are  also  three 
ways  of  reviving  impressions  for  written  words  or  letters. 

(a)  Spontaneous  or  normal. 

(6)  A  train  of  thought  must  first  be  set  going ;  as,  for  instance,  converting 
printed  words  into  written  characters. 

(a)  Mimetic ;  he  can  only  write  from  a  copy. 

Some  operations,  such  as  reading  aloud  and  writing  from  dictation,  require  the 
combined  activity  of  several  centres.  This,  however,  we  have  previously  considered 
in  connection  with  the  subject  of  association  in  the  brain  (see  p.  741). 


CHAPTEE     LVIII 

THE   EYE   AND   VISION 

THE  eyeball  is  contained  in  the  cavity  of  the  skull  called  the  orbit ; 
here  also  are  vessels  and  nerves  for  the  supply  of  the  eyeball, 
muscles  to  move  it,  and  a  quantity  of  adipose  tissue.  In  the  front 
of  the  eyeball  are  the  lids  and  lacrimal  apparatus. 

The  eyelids  consist  of  two  movable  folds  of  skin,  each  of  which  is 
kept  in  shape  by  a  thin  plate  of  fibrous  tissue  called  the  tarsus. 
Along  their  free  edges  are  inserted  a  number  of  curved  hairs  (eye- 
lashes), which,  when  the  lids  are  half  closed,  serve  to  protect  the 
eye  from  dust  and  other  foreign  bodies :  the  tactile  sensibility  of  the 
lids  is  very  delicate.  Imbedded  in  the  tarsus  are  a  number  of  long 
sebaceous  glands  (Meibomian),  the  ducts  of  which  open  near  the  free 
edge  of  the  lid.  In  the  loose  connective  tissue  in  front  of  the 
tarsus,  the  bundles  of  the  orbicularis  muscle  are  situated. 

The  orbital  surface  of  each  lid  is  lined  by  a  delicate,  highly 
sensitive  mucous  membrane  (conjunctiva),  which  is  continuous  with 
the  skin  at  the  free  edge  of  each  lid,  and  after  lining  the  inner 
surface  of  the  eyelid  is  reflected  on  to  the  eyeball,  being  somewhat 
loosely  adherent  to  the  sclerotic  coat.  Its  epithelium,  which  is 
columnar,  is  continued  over  the  cornea  as  its  anterior  epithelium, 
where  it  becomes  stratified.  At  the  inner  edge  of  the  eye  the 
conjunctiva  becomes  continuous  with  the  mucous  lining  of  the 
lacrimal  sac  and  duct,  which  again  is  continuous  with  the  mucous 
membrane  of  the  nose. 

The  eyelids  are  closed  by  the  contraction  of  a  sphincter  muscle 
(orbicularis),  supplied  by  the  facial  nerve ;  the  upper  lid  is  raised  by 
the  levator  palpebrce  superioris,  supplied  by  the  third  nerve. 

The  lacrimal  gland,  composed  of  lobules  made  up  of  acini  resembling 
the  serous  salivary  glands,  is  lodged  in  the  upper  and  outer  angle  of 
the  orbit.  Its  secretion,  which  issues  from  several  ducts  on  the 
inner  surface  of  the  upper  lid,  under  ordinary  circumstances  just 
suffices  to  keep  the  conjunctiva  moist.  It  passes  out  through  two 
small  openings  (puncta  lacrimalia)  near  the  inner  angle  of  the  eye, 

810 


CH.  LVIII.]  THE   EYEBALL  811 

one  in  each  lower  lid,  into  the  lacrimal  sac,  and  thence  along  the  nasal 
duct  into  the  inferior  meatus  of  the  nose.  The  excessive  secretion 
poured  out  under  the  influence  of  an  irritating  vapour  or  painful 
emotion  overflows  the  lower  lid  in  the  form  of  tears.  The  secretory 
nerves  are  contained  in  the  lacrimal  and  subcutaneous  malar  branches 
of  the  fifth  nerve,  and  in  the  cervical  sympathetic. 

The  Eyeball. 

The  eyeball  (fig.  507)  consists  of  the  following  structures : — 


—  Sclerotic  coat. 

—  Choroid  coat. 

________________________  _  —Retina. 

Ciliary  muscle— 


Cornea— 
Anterior  chamber- 

Lens— 

Iris- 

Ciliary  process- 
Ciliary  muscle— 


Fio.  507.— Section  of  the  anterior  four-fifths  of  the  eyeball. 

The  sclerotic,  or  outermost  coat,  is  made  of  connective  tissue  and 
envelops  about  five-sixths  of  the  eyeball :  continuous  with  it,  in  front, 
and  occupying  the  remaining  sixth,  is  the  transparent  cornea  (fig.  508). 
Immediately  within  the  sclerotic  is  the  choroid  coat,  and  within  the 
choroid  is  the  retina.  The  interior  of  the  eyeball  is  filled  by 
the  aqueous  and  vitreous  humours  and  the  crystalline  lens  ;  but,  also, 
there  is  suspended  in  the  interior  a  contractile  and  perforated  cur- 
tain,— the  iris,  which  is  continuous  with  the  choroid;  it  regulates 
the  admission  of  light;  at  the  junction  of  the  sclerotic  and  cornea  is 
the  ciliary  muscle,  the  function  of  which  is  to  adapt  the  eye  for  seeing 
objects  at  various  distances. 

The  Choroid  Coat  is  the  vascular  coat  of  the  eyeball,  and  its 
connective  tissue  contains  abundance  of  branched  pigment  cells.  It 
is  separated  from  the  retina  by  a  fine  elastic  membrane  (membrane  of 
Bruch). 


812 


THE   EYE  AND   VISION 


[CH.  LVIII. 


The  choroid  coat  ends  in  front  in  what  are  called  the  ciliary 
processes  (figs.  509,  510).  These  consist  of  from  70  to  80  meridion- 
ally  arranged  radiating  plaits,  which  consist  of  blood-vessels,  fibrous 
connective  tissue,  and  pigment  corpuscles.  They  are  lined  by  a 

continuation  of  the  membrane  of  Bruch. 
The  ciliary  processes  terminate  at  the 
margin  of  the  lens.  The  ciliary  muscle 
(13,  14,  and  15,  fig.  509),  takes  origin  at 
the  corneo-scleral  junction.  It  is  a  ring 
of  muscle,  3  mm.  broad  and  8  mm.  thick, 
made  up  of  fibres  running  in  three  direc- 
tions, (a)  Meridional  fibres  near  the 
sclerotic  and  passing  to  the  choroid ; 
(5)  radial  fibres  inserted  into  the  choroid 
behind  the  ciliary  processes ;  and  (c)  cir- 
cular fibres  (muscle  of  Muller),  more 
internal ;  they  constitute  a  sphincter. 

The  Iris  is  a  continuation  of  the 
choroid  inwards  beyond  the  ciliary  pro- 
cesses. It  is  a  fibro-muscular  membrane 
perforated  by  a  central  aperture,  the  pupil. 
Posteriorly  is  a  layer  of  pigment  cells 
(uvea),  which  is  a  continuation  forwards 
of  the  pigment  layer  of  the  retina.  The 
iris  proper  is  made  of  connective  tissue 
in  front  with  corpuscles  which  may  or 
may  not  be  pigmented,  and  behind  of 
similar  tissue  supporting  blood-vessels. 
The  pigment  cells  are  usually  well 
developed  here,  as  are  also  many  nerve- 
fibres  radiating  towards  the  pupil.  Sur- 
rounding the  pupil  is  a  layer  of  circular 
unstriped  muscle,  the  sphincter  pupillce. 
In  some  animals  there  are  also  muscle- 
fibres  which  radiate  from  the  sphincter 
in  the  substance  of  the  iris  forming  the 
dilator  pupillce.  The  iris  is  covered  an- 
teriorly by  a  layer  of  epithelium  con- 
tinued upon  it  from  the  posterior  surface 
of  the  cornea. 

The  Lens  is  situated  behind  the  iris,  being  enclosed  in  a  distinct 
capsule,  the  posterior  layer  of  which  is  not  so  thick  as  the  anterior. 
It  is  supported  in  place  by  the-  suspensory  ligament,  fused  to  the 
anterior  surface  of  the  capsule.  The  suspensory  ligament  is  derived 
from  the  hyaloid  membrane,  which  encloses  the  vitreous  humour. 


FIQ.  508.— Vertical  section  of  rabbit's 
cornea,  stained  with  gold  chloride. 
e,  Stratified  anterior  epithelium. 
Immediately  beneath  this  is  the 
anterior  homogeneous  lamina  of 
Bowman,  n,  Nerves  forming  a 
delicate  sub-epithelial  plexus,  and 
sending  up  fine  twigs  between  the 
epithelial  cells  to  end  in  a  second 
plexus  on  the  free  surface;  d, 
Descemet's  membrane,  consisting 
of  a  fine  elastic  layer,  and  a  single 
layer  of  epithelial  cells;  the  sub- 
stance of  the  cornea,  /,  is  seen  to 
be  fibrillated,  and  contains  many 
layers  of  branched  corpuscles,  ar- 
ranged parallel  to  the  free  surface, 
and  here  seen  edgewise. 

(Schofield.) 


CH.  LVIIL] 


THE  LENS 


813 


The  lens  is  made  up  of  a  series  of  concentric  laminae  (fig.  511), 
which,  when  it  has  been  hardened,  can  be  peeled  off  like  the  coats  of 

v      s        s' 

l  ' 

^^  - 


FIG.  509.—  Section  through  the  eye  carried  through  the  ciliary  processes.  1,  Cornea;  2,  membrane  of 
Descemet ;  3,  sclerotic ;  3',  corneo-scleral  junction ;  4,  canal  of  Schlemm ;  5,  vein  ;  6,  nucleated 
network  on  inner  wall  of  canal  of  Schlemm  ;  7,  lig.  pectinatum  iridis,  a  &  c ;  8,  iris ;  9,  pigment  of 
iris  (uvea);  10,  ciliary  processes ;  11,  ciliary  muscle;  12,  choroid  tissue;  13,  meridional,  and  14, 
radiating  fibres  of  ciliary  muscle;  15,  ring-muscle  of  Miiller;  16,  circular  or  angular  bundles  of 
ciliary  muscle.  (Schwalbe.) 

an  onion.     The  laminae  consist  of  long  ribbon-shaped  fibres,  which  in 
the  course  of  development  have  originated  from  cells.     The  fibres 


Fia.  510. — Ciliary  processes,  as  seen  from 
behind.  1,  Posterior  surface  of  the  iris, 
with  the  sphincter  muscle  of  the  pupil ; 
2,  anterior  part  of  the  choroid  coat ;  3, 
one  of  the  ciliary  processes,  of  which 
about  seventy  are  represented. 


FIG.  511. — Laminated  structure  of 
the  crystalline  lens.  The  laminae 
are  split  up  after  hardening  in 
alcohol.  1,  The  denser  central 
part  or  nucleus ;  2,  the  succes- 
sive external  layers.  *. 

(Arnold.) 


are  united  together  by  a  scanty  amount  of  cement  substance.     The 
central  portion  (nucleus)  of  the  lens  is  the  hardest. 

The  epithelium  of  the  lens  consists  of  a  layer  of  cubical  cells 
anteriorly,  which  merge  at  the  equator  into  the  lens  fibres.  The 
development  of  the  lens  explains  this  transition.  The  lens  at  first 


814 


THE   EYE   AND    VISION 


[CH.  LVIII. 


consists  of  a  closed  sac  composed  of  a  single  layer  of  epithelium. 
The  cells  of  the  posterior  part  soon  elongate  forwards  and  obliterate 
the  cavity;  the  anterior  cells  do  not  grow,  but  at  the  edge  they 
become  continuous  with  the  posterior  cells,  which  are  gradually 
developed  into  fibres  (fig.  512).  The  principal  chemical  constituent 
of  the  lens  is  a  protein  of  the  globulin  class  called  crystallin. 


FIG.  512.— Meridional  section  through  the  lens  of  a  rabbit.    1,  Lens  capsule  ;  2,  epithelium  of  lens; 
3,  transition  of  the  epithelium  into  the  fibres ;  4,  lens  fibres.    (Bubuchin.) 

Corneo-scleral  junction. — At  this  junction  the  relation  of  parts 
(fig.  509)  is  so  important  as  to  need  a  short  description.  In  this  neigh- 
bourhood, the  iris  and  ciliary  processes  join  with  the  cornea.  The 
proper  substance  of  the  cornea  and  the  posterior  elastic  lamina 
become  continuous  with  the  iris,  at  the  angle  of  the  iris,  and  the  iris 
sends  forwards  processes  towards  the  posterior  elastic  lamina,  form- 
ing the  ligamentum  pectinatum  iridis,  and  these  join  with  fibres  of 
the  elastic  lamina.  The  epithelial  covering  of  the  posterior  surface 
of  the  cornea  is,  as  we  have  seen,  continuous  over  the  front  of  the 
iris.  At  the  iridic  angle,  the  compact  inner  substance  of  the  cornea 
is  looser,  and  between  the  bundles  are  lymph  spaces  called  the  spaces 
of  Fontana.  They  are  but  little  developed  in  the  human  cornea. 

The  spaces  between  the  bundles  of  corneal  tissue  at  the  angle 
of  the  iris  are  continuous  with  the  larger  lymphatic  space 
of  the  anterior  chamber.  Above  the  angle  at  the  corneo-scleral 
junction  is  a  canal,  which  is  called  the  canal  of  Schlemm.  It 
is  a  lymphatic  channel. 

The  retina  (fig.  513)  apparently  ends  in  front,  near  the  outer 
part  of  the  ciliary  processes,  in  a  finely-notched  edge, — the  ora 
serrata,  but  is  really  represented  by  the  uvea  to  the  very  margin 
of  the  pupil.  The  nerve-cells  in  the  retina  remind  us  that  the  optic, 
like  the  olfactory  nerve,  is  not  a  mere  nerve,  but  an  outgrowth  of 
the  brain. 

In  the  centre  of  the  retina  is  a  round  yellowish  elevated  spot, 
about  2*4  of  an  inch  (1  mm.)  in  diameter,  having  a  depression  in 
the  centre,  called  after  its  discoverer  the  macula  lutea  or  yellow 
spot  of  Scemmering.  The  depression  in  its  centre  is  called  tihefovea 
centralis.  About  ^  of  an  inch  (2 '5  mm.)  to  the  inner  side  of  the 
yellow  spot,  is  the  point  (optic  disc  or  white  spot)  at  which  the  optic 
nerve  leaves  the  eyeball.  The  optic  nerve-fibres  are  the  axons  of  the 


Gil    LVI1I.] 


THE    RETINA 


815 


nerve-cells  of  the  retina;    the  dendrons  of  these  cells  ultimately 
communicate  with  the  visual  nerve-epithelium  (rods  and  cones). 

The  optic  nerve  passes  backwards  to 
the  ventral  surface  of  the  brain  enclosed 
in  prolongations  of  the  membranes,  which 
cover  the  brain.  This  external  sheath  at 
the  exit  of  the  nerve  from  the  eyeball 
becomes  continuous  with  the  sclerotic, 
which  at  this  part  is  perforated  by  holes 
to  allow  of  the  passage  of  the  optic  nerve- 
fibres,  the  perforated  part  being  the 
lamina  cribrosa.  The  fibres  of  the  nerve 
themselves  are  exceedingly  fine,  and  are 
surrounded  by  the  myelin  sheath,  but  do 
not  possess  the  ordinary  external  nerve 
sheath.  In  the  retina  itself  they  have  no 
myelin  sheaths.  In  the  centre  of  the 
nerve  is  a  small  artery,  the  arteria  centralis 
retince.  The  number  of  fibres  in  the  optic 
nerve  is  said  to  be  upwards  of  500,000. 

The  retina  consists  of  certain  ele- 
ments arranged  in  ten  layers  from  within 
outwards  (figs.  513,  514,  515). 

1.  Membrana  limitans  internet. — This 
so-called  membrane  in  contact  with  the 
vitreous  humour  is  formed  by  the  junction 
laterally  of  the  bases  of  the  sustentacular 
or  supporting  fibres  of  Midler,  which  bear 
the  same   relation  to  the   retina  as  the 
neuroglia  does  to  the  brain.     The  char- 
acter  of    these   fibres    may   be   seen   in 
fig.  514. 

2.  Optic  nerve-fibres. — This  layer  is  of  very  varying  thickness  in 
different  parts  of  the  retina :   it  consists  of  non-medullated  fibres 
which   interlace,  and   most   of   which  are   the  axons  of  the  large 
nerve-cells  forming  the  next  layer.     The  fibres  are  supported  by  the 
sustentacular  fibres.     They  are  less  and  less  numerous  anteriorly, 
and  end  at  the  ora  serrata.     They  all  converge  towards  the  optic 
disc,  where  they  leave  the  retina  as  the  optic  nerve. 

3.  Layer  of  ganglion  cells. — This  consists  of  large  multipolar  nerve- 
cells  with  large  and  round  nuclei,  forming  either  a  single  layer,  or  in 
some  parts  of  the  retina,  especially  near  the  macula  lutea,  where  this 
layer  is  very  thick,  it  consists  of  several  strata  of  nerve- cells.     They 
are   arranged   with    their   single   axis-cylinder    processes    inwards. 
These  pass  into  and  are  continuous  with  the  layer  of  optic  nerve- 


FIG.  513.  —  Diagrammatic  section  of 
human  retina  (M.  Schultze).  1,  Mem- 
brana limitans  interna;  2,  layer  of 
optic  nerve-fibres ;  3,  layer  of  optic 
nerve-cells ;  4,  inner  synapse  or  mole- 
cular layer;  5,  inner  nuclear  or 
bipolar  layer;  6,  outer  synapse  or 
molecular  layer;  7,  outer  nuclear 
layer;  8,  membrana  limitans  ex- 
terna ;  9,  layer  of  rods  and  cones ; 
10,  layer  of  pigment  cells. 


816 


THE   EYE   AND   VISION 


[CH.  LV1II. 


fibres.      Externally  the   cells  send   off  several   branched  processes 
which  pass  into  the  next  layer. 

4.  Inner  molecular  layer. — This  presents  a  finely  granulated 
appearance.  It  consists  of  neuroglia  traversed  by  numerous  fibrillar 
processes  of  the  nerve-cells  just  described,  and  the  minute  branch- 
ings of  the  processes  of  the  bipolar  cells  of  the  next  layer. 


Outer  mole- 
cular layer. 


FIG.  514. — Diagram  showing  the  susten- 
tacular  fibres  of  the  retina ;  /,  fibre- 
basket  above  the  external  limiting 
membrane ;  m,  nucleus  of  the  fibre  ; 
r,  base  of  the  fibre. 

(From  M'Kendrick,  after  Stohr.) 


Inner  limb  — 
of  rod. 


Rod  fibre.    .. 


Bipolar  cell.  


FIG.  515. — Diagram  showing  the  nervous  elements 
of  retina.  1,  Nerve-fibre  of  ganglion  cell;  2,  pro- 
cesses of  ganglion  cell  going  outwards  ;  3,  nerve- 
fibre  passing  from  bipolar  cell  in  inner  nuclear 
layer ;  4,  process  of  ganglion  cell  towards  bipolar 
cell;  5,  arborisations  of  fibres  from  rods  and 
cones  with  the  branches  of  bipolar  cells. 

(From  M'Kendrick,  after  Stohr.) 


5.  Inner  nuclear  layer. — This  consists  chiefly  of  numerous  small 
round  cells,  each  with  a  very  small  quantity  of  protoplasm  surround- 
ing a  large  ovoid  nucleus ;  they  are  generally  bipolar,  giving  oft  one 
process  outwards  and  another  inwards.  One  process  passes  inwards 
to  form  a  synapse  with  the  arborisation  of  a  ganglion  cell,  the  other 
outwards  to  similarly  arborise  with  the  branchings  of  the  rod  and 
cone  fibres.  Some  cells,  called  spongioblasts,  or  amacrine  cells,  how- 
ever, only  send  off  one  process,  which  passes  inwards  (fig.  514). 


CH.  LVIII.]  THE  RODS  AND  CONES  817 

The  large  oval  nuclei  (fig.  514)  belonging  to  the  Miillerian  fibres 
occur  in  this  layer. 

6.  Outer  molecular  layer. — This  layer  closely  resembles  the  inner 
molecular  layer,  but  is  much  thinner.     It  contains  the  branchings  of 
the  rod  and  cone  fibres  on  the  one  hand  and  of  the  bipolar  cells  on 
the  other. 

7.  External  nuclear  layer. — This  layer   consists   of   small   cells 
resembling  at  first  sight  those  of  the  internal  nuclear  layer ;  they 
are  classed  as  rod  and  cone  granules,  according  as  they  are  connected 
with  the  rods  and  cones  respectively,  and  will  be  described  with 
them.     They  are  lodged  in  the  meshes  of  a  frame-work,  which  is 
formed  by  the  breaking  up  of  the  Miillerian  fibres. 

8.  Membrana  limitans  externa. — This  is  a  well-defined  membrane, 
marking  the  internal  limit  of  the  rod  and  cone  layer,  and  made  up 
of  the  junction  of  the  sustentacular  or  Miillerian  fibres  externally. 

9.  Layer  of  rods  and  cones. — This  layer  is  the  nerve-epithelium 
of  the  retina.     It  consists  of  two  kinds  of  cells,  rods  and  cones, 
which  are  arranged  at  right  angles  to  the  external  limiting  mem- 
brane, and  supported  by  hairlike  processes  (basket)  proceeding  from 
the  latter  for  a  short  distance  (fig.  514). 

Each  rod  (fig.  515)  is  made  up  of  two  parts,  very  different  in 
structure,  called  the  outer  and  inner  limbs.  The  outer  limb  of  the 
rods  is  about  30  /x,  long  and  2  /UL  broad,  is  transparent,  and  doubly 
refracting.  It  is  said  to  be  made  up  of  fine  superimposed  discs. 
It  stains  brown  with  osmic  acid  but  not  with  haematoxylin,  and 
resembles  in  some  ways  the  myelin  sheath  of  a  medullated  nerve. 
It  is  the  part  of  the  rod  in  which  the  pigment  called  visual  purple  is 
found.  In  some  animals,  a  few  rods  have  a  greenish  pigment  instead. 
The  inner  limb  is  about  as  long  but  slightly  broader  than  the  outer, 
is  longitudinally  striated  at  its  outer,  and  granular  at  its  inner  part. 
It  stains  with  haematoxylin,  but  not  with  osmic  acid.  Each  rod  is 
connected  internally  with  a  rod  fibre,  very  fine,  but  here  and  there 
varicose;  in  the  middle  of  the  fibre  is  a  rod  granule,  really  the 
nucleus  of  the  rod,  striped  broadly  transversely,  and  situated  about 
the  middle  of  the  external  nuclear  layer;  the  internal  end  of  the 
rod  fibre  terminates  in  branchings  in  the  outer  molecular  layer. 

Each  cone  (fig.  515),  like  the  rods,  is  made  up  of  two  limbs, 
outer  and  inner.  The  outer  limb  is  tapering  and  not  cylindrical  like 
the  corresponding  part  of  the  rod,  and  about  one-third  only  of  its 
length.  There  is,  moreover,  no  visual  purple  found  in  the  cones. 
The  inner  limb  of  the  cone  is  broader  in  the  centre.  It  is  proto- 
plasmic, and  under  the  influence  of  light  has  been  seen  to  execute 
movements.  In  birds,  reptiles  and  amphibia,  there  is  often  a 
coloured  oil  globule  present  here.  Each  cone  is  in  connection  by 
its  internal  end  with  a  cone  fibre,  which  has  much  the  same  structure 


818 


THE    EYE   AND    VISION 


[CII    LV1II. 


as  the  rod  fibre,  but  is  stouter  and  has  its  nucleus  (cone  granule) 
quite  near  to  the  external  limiting  membrane.  Its  inner  end 
terminates  by  branchings  in  the  external  molecular  layer. 

In  the  rod  and  cone  layer 
of  birds,  the  cones  usually  pre- 
dominate largely  in  number, 
whereas  in  man  the  rods  are  by 
far  the  more  numerous,  except 
in  the  fovea  centralis,  where  cones 
only  are  present.  The  number 
of  cones  has  been  estimated  at 
3,000,000. 

10.  Pigment-cell  layer  consists 
of  a  single  layer  of  polygonal  cells, 
mostly  six-sided,  which  send  down 
a  beard-like  fringe  to  surround  the 
outer  ends  of  the  rods.  It  is  this 
layer  which  is  continuous  with  the 
uvea,  where,  however,  the  cells  be- 
come rounded,  and  arranged  two 
or  three  deep. 

Differences  in  Structure  of  differ- 
ent parts. — Towards  the  centre  of 
the  macula  lutea  all  the  layers 
of  the  retina  become  greatly 
thinned  out  and  almost  disappear,  except  the  rod  and  cone  layer, 
and  at  the  fovea  centralis  the  rods  disappear,  and  the  cones  are  long 


Fio.  516.— The  posterior  half  of  the  retina  of 
the  left  eye,  viewed  from  before;  s,  The  cut 
edge  of  the  sclerotic  coat ;  ch,  the  choroid ;  r, 
the  retina ;  in  the  interior  at  the  middle  the 
macula  lutea  with  the  depression  of  the  fovea 
centralis  is  represented  by  a  slight  oval  shade ; 
towards  the  left  side  the  light  spot  indicates 
the  colliculus  or  eminence  at  the  entrance  of 
the  optic  nerve,  from  the  centre  of  which  the 
arteria  centralis  is  seen  spreading  its  branches 
into  the  retina,  leaving  the  part  occupied  by 
the  macula  comparatively  free.  (After  Henle.) 


FIG.  517.— Pigment-cells  from  the  retina. 
A,  Cells  still  cohering,  seen  on  their 
surface ;  a,  nucleus  indistinctly  seen. 
In  the  other  cells  the  nucleus  is  con- 
cealed by  the  pigment  granules.  B, 
Two  cells  seen  in  profile ;  a,  the  outer 
or  posterior  part  containing  scarcely 
any  pigment,  x  370.  (Henle.) 


in.l.c. 


FIG.  518. — Diagram  of  a  section  through  half  the 
fovea  centralis.  2,  Ganglionic  layer;  4,  inner 
nuclear;  6,  outer  nuclear  layer,  the  cone  fibres 
forming  the  so-called  external  fibrous  layer; 
7,  cones;  m.l.e.,  membrana  limitans  externa ; 
m.l.i.,  membrana  limitans  interna.  (Schafer  and 
Golding  Bird.) 


and  narrow.  At  the  margin  of  the  fovea  the  layers  increase  in 
thickness,  and  in  the  rest  of  the  macula  lutea  are  thicker  than 
elsewhere.  The  ganglionic  layer  is  especially  thickened,  the  cells 


CH.    LVIII.J 


THE   FOVEA 


819 


being  six  to  eight  deep  (2,  fig.  518).  The  bipolar  inner  granules 
(cone  nuclei)  are  obliquely  disposed  (figs.  518  and  519)  on  the 
course  of  the  cone  fibres,  and  are  situated  at  some  distance  from 
the  membrana  limitans  externa,  which  is  cupped  towards  the  fovea 
(fig.  518).  The  yellow  tint  of  the  macula  is  due  to  a  diffuse  colouring 
matter  in  the  interstices  of  the  four  or  five  inner  layers ;  it  is  absent 
at  the  centre  of  the  fovea. 

It  is  important  to  notice  what  is  clearly  brought  out  in  fig.  519, 
that  at  the  fovea  each  cone  is  connected  to  a  separate  chain  of 


FIG.  519.— Scheme  of  the  retinal  elements.  A,  cones  of  the  fovea  centralis;  B,  granules  (nuclei)  of 
these  cones  ;  C,  synapse  between  the  cones  and  bipolar  cells  in  external  molecular  layer ;  D,  synapse 
between  the  bipolar  and  ganglion  cells  in  the  internal  molecular  layer ;  a  and  b,  rods  and  cones  in 
other  regions  of  the  retina ;  c,  bipolar  cell  destined  for  the  cones ;  d,  bipolar  cell  destined  for  the 
rods ;  B,  e,  ganglion  cells ;  /,  spongioblast ;  g,  efferent  fibre  (?  trophic),  originating  from  the  cell  m, 
in  geniculate  body;  h,  optic  nerve;  i,  terminal  arborisations  of  optic  nerve-fibres  in  geniculate 
body ;  j,  fibres  from  the  cells  of  geniculate  body  on  the  way  to  cerebral  cortex.  (R.  y  Cajal.) 

neurons,  whereas  in  other  regions  the  rods  and  cones  are  connected 
in  groups  to  these  chains ;  this  explains  the  greater  sensitiveness  of 
foveal  vision. 

At  the  ora  serrata  the  layers  are  not  perfect,  and  disappear  in 
this  order:  nerve-fibres  and  ganglion  cells,  then  the  rods,  leaving 
only  the  inner  limbs  of  the  cones,  next  these  cease,  then  the  outer 
molecular  layer,  the  inner  and  outer  nuclear  layers  coalescing,  and 
finally  the  inner  molecular  layer  also  is  unrepresented. 

At  the  pars-ciliaris  retince,  the  retina  consists  of  a  layer  of 
columnar  cells,  which  probably  represent  the  Miillerian  fibres.  These 
cells  externally  are  in  contact  with  the  pigment  layer  of  the  retina, 
which  is  continued  over  the  ciliary  processes  and  back  of  the  iris. 
Nervous  structures  are  absent. 

At  the  exit  of  the  optic  nerve  the  only  structures  present  are 
nerve-fibres. 

The  anterior  chamber  is  the  space  behind  the  cornea  and  in  front 
of  the  iris.  It  is  filled  with  aqueous  humour  (dilute  lymph). 

The  vitreous  humour,  which  is  a  jelly-like  connective  tissue  (see 
p.  36),  is  situated  behind  the  crystalline  lens.  It  is  enclosed  in  a 
membrane  called  membrana  hyaloidea,  which  in  front  is  continuous 


820  THE   EYE  AND   VISION  [CH.  LVttL 

with  the  capsule  of  the  lens ;  round  the  edge  of  the  lens  the  canal 
left  is  called  the  Canal  of  Petit  (fig.  507,  p.  811),  the  membrane  itself 
being  the  Zonule  of  Zinn.  The  hyaloid  membrane  separates  the 
vitreous  from  the  retina. 

Blood-vessels  of  the  Eyeball. — The  eye  is  very  richly  supplied  with  blood- 
vessels. In  addition  to  the  conjunctival  vessels  which  are.  derived  from  the  palpe- 
bral  and  lacriraal  arteries,  there  are  at  least  two  other  distinct  sets  of  vessels 
supplying  the  tunics  of  the  eyeball. 

(1)  These  are  the  short  and  long  posterior  ciliary  arteries  which   pierce  the 
sclerotic  in  the  posterior  half  of  the  eyeball,  and  the  anterior  ciliary  which  enter 
near  the  insertions  of  the  recti.     These  vessels  anastomose  and  form  a  rich  choroidal 
plexus ;   they  also  supply  the  iris  and  ciliary  processes,  forming  a  highly  vascular 
circle  round  the  outer  margin  of  the  iris  and  adjoining  portion  of  the  sclerotic.     The 
distinctness  of  these  vessels  from  those  of  the  conjunctiva  is   well  seen   in  the 
difference  between  the  bright  red  of  blood-shot  eyes  (conjunctival  congestion),  and 
the  pink  zone  surrounding  the  cornea  which  indicates  deep-seated  ciliary  congestion. 

(2)  The  retinal  vessels  (fig.  516)  are  derived  from  the  arteria  centralis  retinae, 
which  enters  the  eyeball  along  the  centre  of  the  optic  nerve.     They  ramify  all  over 
the  retina,  in  its  inner  layers.     They  can  be  seen  by  ophthalmoscopic  examination. 

The  Eye  as  an  Optical  Instrument. 

In  a  photographic  camera  images  of  external  objects  are  thrown 
upon  a  screen  at  the  back  of  a  box,  the  interior  of  which  is  painted 
black.  In  the  eye,  the  camera  is  represented  by  the  eyeball  with  its 
black  pigment,  the  screen  by  the  layer  of  rods  and  cones  of  the  retina, 
and  the  lens  by  the  refracting  media.  In  the  case  of  the  camera, 
the  screen  is  enabled  to  receive  clear  images  of  objects  at  different 
distances,  by  an  apparatus  for  focussing.  The  corresponding  con- 
trivance in  the  eye  is  called  accommodation. 

The  iris,  which  allows  more  or  less  light  to  pass  into  the  eye, 
corresponds  with  the  diaphragms  used  in  the  photographic  apparatus. 

The  refractive  media  are  the  cornea,  aqueous  humour,  crystalline 
lens,  and  vitreous  humour.  The  most  refraction  or  bending  of  the 
rays  of  light  occurs  where  they  pass  from  the  air  into  the  cornea ;  they 
are  again  bent  slightly  in  passing  through  the  lens.  Alterations  in 
the  anterior  curvature  of  the  lens  lead  to  accommodation. 

We  may  first  consider  the  refraction  through  a  transparent 
spherical  surface,  separating  two  media  of  different  density. 

The  rays  of  light  which  fall  upon  the  surface  exactly  perpendicu- 
larly do  not  suffer  refraction,  but  pass  through,  cutting  the  optic 
axis  (0  A,  fig.  520),  a  line  which  passes  exactly  through  the  centre 
of  the  surface,  at  a  certain  point,  the  nodal  point  (fig.  520,  N),  or 
centre  of  curvature.  Any  rays  which  do  not  so  strike  the  curved 
surface  are  refracted  towards  the  optic  axis.  Kays  which  impinge 
upon  the  spherical  surface  parallel  to  the  optic  axis,  will  meet  at  a 
point  behind,  upon  the  said  axis  which  is  called  the  chief  posterior 
focus  (fig.  520,  F-L);  and  again  there  is  a  point  on  the  optic  axis  in 
front  of  the  surface,  rays  of  light  from  which  so  strike  the  surface 


CH.  LVIII.]  THE   SCHEMATIC   EYE  821 

that  they  are  refracted  in  a  line  parallel  with  the  axis  d  /";  this 
point  (fig.  520,  F2)  is  called  the  chief  anterior  focus.  The  optic  axis 
cuts  the  surface  at  what  is  called  the  principal  point. 


FIG.  520.— Diagram  of  a  simple  optical  system  (after  M.  Foster).  The  curved  surface,  b,  d,  is  supposed 
to  separate  a  less  refractive  medium  towards  the  left  from  a  more  refractive  medium  towards  the 
right. 

It  is  quite  obvious  that  the  eye  is  a  much  more  complicated 
optical  apparatus  than  the  one  described  in  the  figure.  It  is,  how- 
ever, possible  to  reduce  the  refractive  surfaces  and  media  to  a  simpler 
form  when  the  refractive  indices  of  the  different  media  and  the 
curvature  of  each  surface  are  known.  These  data  are  as  follows : — 

Index  of  refraction  of  cornea  .        .         .         .  =     1'37 

„                  „           aqueous  and  vitreous  .  =     1  "34  to  1  '36 

,  _  /I '4  in  outer  to  1  '45 

-  \     in  inner  part. 

Radius  of  curvature  of  cornea .         .         .         .  =     7 '8  mm. 

„                  „           anterior  surface  of  lens  =  10       „ 

„                  „           posterior      .         .         .  =     6       „ 
Distance  from  anterior  surface  of  cornea  to 

anterior  surface  of  lens          .        .         .         .  =     3'6    „ 
Distance  from  posterior  surface  of  cornea  to 

posterior  surface  of  lens        .         .        .        .  =     7*2    „ 
Distance  from   posterior   surface   of  lens  to 

retina =  15 '0    „ 

With  these  data  it  has  been  found  comparatively  easy  to  reduce 
by  calculation  the  different  surfaces  of  different  curvature  into  one 
mean  curved  surface  of  known  curvature,  and  the  differently  refracting 
media  into  one  mean  medium  the  refractive  power  of  which  is  known. 

The  simplest  so-called  schematic  eye  formed  upon  this  principle, 
suggested  by  Listing  as  the  reduced  eye,  has  the  following  dimen- 
sions : — 

From  anterior  surface  of  cornea  to  the  principal  point  =     2'3448  mm. 
From  the  nodal  point  to  the  posterior  surface  of  lens  *4764    „ 

Posterior  chief  focus  lies  behind  cornea       .         .        .  =  22'8237    ,, 

Anterior  chief  focus  in  front  of  cornea          .         .         .  =   12'8326    ,, 

Radius  of  curvature  of  ideal  surface     .         .  .  =     5*1248    „ 

The  term  index  of  refraction  means  the  ratio  of  the  sine  of  the 


822 


THE   EYE  AND   VISION 


[CH.  LYIII. 


angle  of  incidence  to  that  of  the  angle  of  refraction ;  this  is  explained 
in  the  small  text  beneath  fig.  521. 

In  this  reduced  or  simplified  eye,  the  principal  posterior  focus, 
about  23  mm.  behind  the  spherical  surface,  would  correspond  to  the 


FIG.  521.— If  P  P'  is  a  line  which  separates  two  media,  the  lower  one  being  the  denser,  and  A  O  is  a  ray 
of  light  falling  on  it,  it  is  bent  at  O  towards  the  normal  or  perpendicular  line  N  N'.  A  O  is  called 
the  incident  ray,  and  O  B  the  refracted  ray ;  A  O  N  is  called  the  angle  of  incidence  (i),  N'  O  B  the 
angle  of  refraction  (r).  If  any  distance  O  X  is  measured  off  along  O  A,  and  an  equal  distance  O  X, 

along  O  B,  and  perpendiculars  drawn  to  N  N';  then-^p—  index  of  refraction. 

position  of  the  retina  behind  the  anterior  surface  of  the  cornea.     The 

refracting   surface  would  be  situated   about  midway  between   the 

posterior  surface  of  the  cornea  and  the  anterior  surface  of  the  lens. 

The  optical  axis  of  the  eye  is  a  line  drawn  through  the  centres  of 

curvature  of  the  cornea  and  lens, 
prolonged  backwards  to  touch  the 
retina  between  the  porus  opticus 
and  f ovea  centralis,  and  this  differs 
from  the  visual  axis  which  passes 
through  the  nodal  point  of  the 
reduced  eye  to  the  fovea  centralis ; 
this  forms  an  angle  of  5°  with 
the  optical  axis.  But  for  practical 
purposes  the  optical  axis  and  the  visual  axis  may  be  considered  to 
be  identical. 

The  visual  or  optical  angle  (fig.  522)  is  included  between  the  lines 


FIG.  522.— Diagram  of  the  optical  angle. 


CH.  LVIII.] 


FORMATION    OF    IMAGES 


823 


drawn  from  the  borders  of  any  object  to  the  nodal  point;  if  the 
lines  are  prolonged  backwards  they  include  an  equal  angle.  It  has 
been  shown  by  Helmholtz  that  the  smallest  angular  distance  between 
two  points  which  can  be  appreciated  as  two  distinct  points  =  50 
seconds,  the  size  of  the  retinal  image  being  3'65  /x ;  this  is  a  little 
more  than  the  diameter  of  a  cone  at  the  fovea  centralis  which  =  3  /x, 
the  distance  between  the  centres  of  two  adjacent  cones  being  =  4  JUL. 
If  the  two  points  are  so  close  together  that  they  subtend  a  visual 
angle  less  than  50  seconds,  both  images  will  fall  upon  one  cone,  and 
the  two  points  will  therefore  appear  as  one. 

Any  object,  for  example,  the  arrow  A  B  (fig.  523),  may  be  con- 
sidered as  a  series  of  points  from  each  of  which  a  pencil  of  light 
diverges  to  the  eye.  Take,  for  instance,  the  rays  diverging  from  the 
tip  of  the  arrow  A ;  C  C  represents  the  curvature  of  the  schematic 
or  reduced  eye ;  the  ray  which  passes  through  the  centre  of  the  circle 


Fio.  523.— Diagram  of  the  course  of  the  rays  of  light,  to  show  how  an  Image 'is  formed  upon  the  retina. 
The  surface  C  C  should  be  supposed  to  represent  the  ideal  curvature. 

of  which  C  C  is  part  is  not  refracted;  this  point  is  represented  as 
an  asterisk  in  fig.  523 ;  it  is  near  the  posterior  surface  of  the  crystal- 
line lens ;  the  ray  A  C,  which  is  parallel  to  the  optic  axis  0  0',  is 
refracted  through  the  principal  posterior  focus  P,  and  cuts  the  first 
ray  at  tha  point  A'  on  the  retina.  All  the  other  rays  from  A  meet 
at  the  same  point.  Similarly  the  other  end  of  the  arrow  B  is  focussed 
at  B',  and  rays  from  all  other  points  have  corresponding  focusses. 

It  will  thus  be  seen  that  an  inverted  image  of  external  objects  is 
formed  on  the  retina.  The  retina  is  a  curved  screen,  but  the  images 
fall  only  on  a  small  area  of  the  retina  under  normal  circumstances ; 
hence,  for  practical  purposes,  this  small  area  may  be  regarded  as  flat. 

The  question  then  arises,  Why  is  it  that  objects  do  not  appear  to 
us  to  be  upside  down  ?  This  cannot  be  satisfactorily  answered  without 
entering  into  matters  which  require  a  previous  psychological  train- 
ing. Suffice  it  to  say  here  that  the  localisation  of  objects  in  space 
depends  not  only  on  the  retina,  but  also  on  tactile  and  general 


824 


THE   EYE   AND    VISION 


[CH.  LVIIL 


experience;  that  the  mind  localises  objects  with  reference  to  its 
own  body,  and  that  from  the  first  it  knows  nothing  of  the  inversion 
of  the  retinal  image,  as  its  powers  of  localisation  only  appear  with 
developing  general  experience. 

ACCOMMODATION 

The  power  of  accommodation  is  primarily  due  to  an  ability  to 
vary  the  shape  of  the  lens ;  its  front  surface  becomes  more  or  less 
convex,  according  as  the  distance  of  the  object  looked  at  is  near  or 
far.  The  nearer  the  object,  the  more  convex,  up  to  a  certain  limit, 

the  front  surface  of  the  lens  becomes,  and 
vice  versd ;  the  back  surface  takes  no  share 
in  the  production  of  the  effect  required. 
The  posterior  surface,  which  during  rest  is 
more  convex  than  the  anterior,  is  thus  ren- 
dered the  less  convex  of  the  two  during 
accommodation.  The  following  simple  ex- 
periment illustrates  this  point :  If  a  lighted 
candle  be  held  a  little  to  one  side  of  a 
person's  eye  an  observer  looking  at  the  eye 
from  the  other  side  sees  three  images  of  the 
CftunTthe  anterior  surface" of  flame  (fig.  524).  The  first  and  brightest  is 

lens;  3,  from  the  posterior  sur-       /*\  fi  ,     •  «  iiji 

face  of  lens.  (1)  a  small  erect  image  formed  by  the  an- 

terior convex  surface   of   the  cornea;   the 

second  (2)  is  also  erect,  but  larger  and  less  distinct  than  the  pre- 
ceding, and  is  formed  at  the  anterior  convex  surface  of  the  lens; 
the  third  (3)  is  smaller,  inverted,  and  indistinct;  it  is  formed  at 
the  posterior  surface  of  the  lens,  which  is  concave  forwards,  and 
therefore,  like  all  concave  mirrors,  gives  an  inverted  image.  If 
now  the  eye  under  observation  is  made  to  look  at  a  near  object,  the 
second  image  becomes  smaller,  clearer,  and  approaches  the  first.  If 


FIG  .  525.— Diagram  of  Sanson's  images.  A,  When  the  eyes  are  not,  and  B,  when  they  are  focussed  for 
near  objects.  The  fig.  to  the  right  in  A  and  B  is  the  inverted  image  from  the  posterior  surface  of 
the  lens. 

the  eye  is  now  adjusted  for  a  far  point,  the  second  image  enlarges 
again,  becomes  less  distinct,  and  recedes  from  the  first.     In  both 


CH.  LVIIL] 


ACCOMMODATION 


825 


cases  the  first  and  third  images  remain  unaltered  in  size,  distinct- 
ness, and  position.  This  proves  that  during  accommodation  for  near 
objects  the  curvature  of  the  cornea,  and  of  the  posterior  surface  of  the 
lens,  remain  unaltered,  while  the  anterior  surface  of  the  lens  becomes 
more  convex  and  approaches  the  cornea. 

The  experiment  is  more  striking  when  two  bright  images  (repre- 
sented by  arrows  in  fig.  525)  are  used ;  the  two  images  from  the  front 
surface  of  the  lens  during  accommodation  not  only  approach  those 
from  the  cornea,  but  also  approach  one  another,  and  become 
somewhat  smaller.  (Sansoris  Images.)  Helmholtz's  Phakoscope 


Fio.  526. — Phakoscope  of  Helmholtz.  At  B  B'  are  two  prisms,  by  which  the  light  of  a  candle  is  con- 
centrated on  the  eye  of  the  person  experimented  with,  which  is  looking  through  a  hole  in  the  third 
angle  of  the  box  opposite  to  the  window  C.  A  is  the  aperture  for  the  eye  of  the  observer.  The 
observer  notices  three  double  images,  represented  by  arrows,  in  fig.  525,  reflected  from  the  eye 
under  examination  when  the  eye  is  fixed  upon  a  distant  object ;  the  position  of  the  images  having 
been  noticed,  the  eye  is  made  to  focus  a  near  object,  such  as  a  reed  pushed  up  at  C ;  the  images 
from  the  anterior  surface  of  the  lens  will  be  observed  to  move  as  described  in  the  text. 

(fig.   526)   is   a    box    with   arrangements    for    demonstrating    this 
experiment. 

Mechanism  of  Accommodation. — The  lens  having  no  inherent 
power  of  contraction,  its  changes  of  outline  must  be  produced  by 
some  power  from  without;  this  power  is  supplied  by  the  ciliary 
muscle.  Its  action  is  to  draw  forwards  the  choroid,  and  by  so 
doing  to  slacken  the  tension  of  the  suspensory  ligament  of  the 
lens  which  arises  from  it.  The  anterior  surface  of  the  lens  is 
kept  flattened  by  the  action  of  this  ligament.  The  ciliary  muscle 
during  accommodation,  by  diminishing  the  tension  of  this  ligament, 
diminishes  to  a  proportional  degree  the  flattening  of  which  it  is  the 


826  THE   EYE   AND   VISION  [CH.  LV11I. 

cause.  On  diminution  or  cessation  of  the  action  of  the  ciliary 
muscle,  the  lens  returns  to  its  former  shape,  by  virtue  of  its  elas- 
ticity (fig.  527).  From  this  it  will  appear  that  the  eye  is  usually 


FIG.  527. — Diagram  representing  by  dotted  lines  the  alteration  in  the  shape  of  the  lens  on  accommo- 
dation for  near  objects.    (E.  Landolt.) 

focussed  for  distant  objects.  In  viewing  near  objects  the  ciliary 
muscle  contracts ;  the  ciliary  muscle  relaxes  on  withdrawal  of  the 
attention  from  near  to  distant  objects. 

It  is  possible  to  calculate  the  curvature  of  the  lens  or  cornea  in  the  body,  by 
measuring  the  size  of  the  image  of  an  object  upon  it  The  radius  (r)  of  curvature 

of  a  convex  reflecting  surface  is  given  by  the  formula  r= —  ;  a  is  the  distance  of 

c 

the  object  from  the  surface,  b  the  diameter  of  the  image,  and  c  that  of  the  object. 
a  and  c  are  easily  measured  ;  b  is  measured  by  Helmholtz's  ophthalmometer,  the 
principle  of  which  is  as  follows : — If  a  line  is  looked  at  through  a  plate  of  glass 
placed  obliquely  between  it  and  the  eye,  the  line  is  shifted  sideways  to  either  right 
or  left ;  if  the  glass  plate  is  then  placed  obliquely  at  right  angles  to  its  previous 
position,  the  line  is  shifted  in  the  opposite  direction.  In  the  ophthalmometer  there 
are  two  glass  plates  intersecting  each  other  at  an  angle;  the  image  of  a  bright 
horizontal  line  upon  the  lens  or  cornea  is  looked  at  through  the  junction  between 
the  two  plates  ;  one  plate  shifts  the  image  to  the  right,  the  other  to  the  left ;  the 
angle  between  the  two  plates  is  altered  until  the  line  appears  as  two  distinct  lines 
just  touching  each  other.  The  amount  of  shifting  of  each,  which  must  therefore  be 
half  the  length  of  the  image  of  the  line,  can  be  easily  calculated  if  the  thickness  of 
the  glass  plates,  their  refractive  index,  and  the  angle  between  them  are  known. 
Double  this  result  gives  the  size  of  the  image  on  the  surface  under  investigation. 

Range  of  Distinct  Vision.  Near -point. — In  every  eye  there  is  a 
limit  to  the  power  of  accommodation.  If  a  book  be  brought  nearer 
and  nearer  to  the  eye,  the  type  at  last  becomes  indistinct,  and  cannot 
be  brought  into  focus  by  any  effort  of  accommodation,  however 
strong.  This,  which  is  termed  the  near-point,  can  be  determined  by 
the  following  experiment  (Scheiner).  Two  small  holes  are  pricked  in 
a  card  with  a  pin  not  more  than  a  twelfth  of  an  inch  (2  mm.)  apart ; 
at  any  rate  their  distance  from  each  other  must  not  exceed  the 
diameter  of  the  pupil.  The  card  is  held  close  in  front  of  the  eye, 


CH.  LYIII.]  ACCOMMODATION  827 

and  a  small  needle  viewed  through  the  pin-holes.  At  a  moderate 
distance  it  can  be  clearly  focussed,  but  when  brought  nearer,  beyond 
a  certain  point,  the  image  appears  double,  or  at  any  rate  blurred. 
This  point  where  the  needle  ceases  to  appear  single  is  the  near-point. 
Its  distance  from  the  eye  can  of  course  be  readily  measured.  It  is 
usually  about  5  or  6  inches  (13  cm.).  In  the  accompanying  figure 
(fig.  528)  the  lens  b  represents  the  refractive  apparatus  of  the  eye ; 
e  and  /  the  two  pin-holes  in  the  card,  nn  the  retina ;  a  represents  the 
position  of  the  needle.  When  the  needle  is  at  a  moderate  distance, 
the  two  pencils  of  light  coming  through  e  and  /  are  focussed  at  a 
single  point  on  the  retina  nn.  If  the  needle  is  brought  nearer  than 
the  near-point,  the  strongest  effort  of  accommodation  is  not  sufficient 
to  focus  the  two  pencils,  they  meet  at  a  point  behind  the  retina.  The 
effect  is  the  same  as  if  the  retina  were  shifted  forward  to  mm.  Two 
images  h,  g  are  formed,  one  from  each  hole.  It  is  interesting  to  note 


FIG.  528. — Diagram  of  experiment  to  ascertain  the  minimum  distance  of  distinct  vision. 

that  when  two  images  are  produced,  the  lower  one  g  really  appears 
in  the  position  Q,  while  the  upper  one  appears  in  the  position  p.  This 
may  be  readily  verified  by  covering  the  holes  in  succession. 

During  accommodation  two  other  changes  take  place  in  the  eyes : 
(1)  The  eyes  converge  owing  to  the  action  of  the  internal  rectus  muscle 
of  each  eyeball.  (2)  The  pupils  contract. 

The  contraction  of  all  of  the  muscles  which  have  to  do  with 
accommodation,  viz.,  of  the  ciliary  muscle,  of  the  internal  recti 
muscles,  and  of  the  sphincter  pupillae,  is  under  the  control  of  the 
third  nerve.  It  should  further  be  noted  that  although  the  act  is  a 
voluntary  one,  the  fibres  of  the  ciliary  muscle  and  of  the  sphincter 
pupillse  are  of  the  plain  variety. 

The  account  of  accommodation  as  given  in  the  preceding  pages  is  true  for  man 
and  other  mammals,  birds,  and  certain  reptiles. 

Beer  has,  however,  shown  that  in  many  animals  lower  in  the  scale,  the 
mechanism  of  accommodation  varies  a  good  deal,  and  is  often  very  different  from 
that  just  described,  consisting,  in  fact,  in  a  power  of  altering  the  distance  between 
the  lens  and  the  retina. 

In  bony  fishes,  the  eye  at  rest  is  accommodated  for  near  objects ;  in  focussing 
for  distant  objects  the  lens  is  drawn  nearer  to  the  retina  by  a  special  muscle  called 


828  THE   EYE  AND   VISION  [CH.  LVIII. 

the  retractor  lentis.  In  cephalopods  the  same  occurs,  but  the  retractor  lentis  is 
absent ;  here  the  approach  of  the  lens  to  the  retina  is  brought  about  by  an  alteration 
of  intra-ocular  tension.  In  Amphibia  and  most  snakes,  the  eye  at  rest  is  focussed 
for  distant  objects;  in  accommodating  for  near  objects  the  lens,  by  alteration  of 
intra-ocular  tension,  is  brought  forward,  that  is,  the  distance  between  it  and  the 
retina  is  increased.  There  appear  to  be  not  a  few  animals  in  all  classes  which  do  not 
possess  the  power  of  accommodation  at  all.  Indeed,  Barrett  states  this  is  so  for 
most  mammals. 

DEFECTS  IN  THE  OPTICAL  APPARATUS 

Under  this  head  we  may  consider  the  defects  known  as  (1) 
Myopia,  (2)  Hypermetropia,  (3)  Astigmatism,  (4)  Spherical  Aber- 
ration, (5)  Chromatic  Aberration,  and  (6)  Presbyopia. 

The  normal  (emmetropic)  eye  is  so  adjusted  that  at  rest  parallel 
rays  are  brought  exactly  to  a  focus  on  the  retina  (1,  fig.  529). 
Hence  all  objects  except  near  ones  (practically  ail  objects  more  than 
twenty  feet  off)  are  seen  without  any  effort  of  accommodation ;  in 
other  words,  the  far-point  of  the  normal  eye  is  at  an  infinite  distance. 
In  viewing  near  objects  we  are  conscious  of  the  effort  (the  contraction 
of  the  ciliary  muscle)  by  which  the  anterior  surface  of  the  lens  is 
rendered  more  convex,  and  rays  which  would  otherwise  be  focussed 
behind  the  retina  are  converged  upon  the  retina  (see  dotted  lines, 
2,  fig.  529). 

1.  Myopia  (short-sight),  (4,  fig.  529). — This  defect  is  due  to  an 
abnormal  elongation  of  the  eyeball.     The  retina  is  too  far  from  the 
lens,  and  consequently  parallel  rays  are  focussed  in  front  of  the 
retina,  and,  crossing,  form  little  circles  on  the  retina ;  thus  the  images 
of  distant  objects  are  blurred  and  indistinct.     The  eye  is,  as  it  were, 
permanently  adjusted  for  a  near-point.     Eays  from  a  point  near  the 
eye  are  exactly  focussed  on  the  retina.     But  those  which  issue  from 
any  object  beyond  a  certain  distance  (far-point)  cannot  be  distinctly 
focussed.     This  defect  is  corrected  by  concave  glasses  which  cause  the 
rays  entering  the  eye  to  diverge :  hence  they  do  not  come  to  a  focus 
so  soon.     Such  glasses,  of  course,  are  only  needed  to  give  a  clear 
vision  of  distant  objects.     For  near  objects,  except  in  extreme  cases, 
they  are  not  required. 

2.  Hypermetropia  (3,  fig.  529). — This  is  the  reverse  defect.     The 
eyeball  is  too  short.     Parallel  rays  are  focussed  behind  the  retina : 
an  effort  of  accommodation  is  required  to  focus  even  parallel  rays  on 
the  retina ;  and  when  they  are  divergent,  as  in  viewing  a  near  object, 
the  accommodation  is  insufficient   to   focus   them.     Thus,  in  well- 
marked  cases,  distant  objects  require  an  effort  of  accommodation,  and 
near  ones  a  very  powerful  effort,  and  the  ciliary  muscle  is,  therefore, 
constantly  acting.     This  defect  is  obviated   by  the   use   of   convex 
glasses,  which  render  the  pencils  of  light  more  convergent.     Such 
glasses  are,  of  course,  especially  needed  for  near  objects,  as  in  reading, 


cfi.  LVIIL] 


ERRORS   OF  REFRACTION 


829 


etc.     They  rest  the  eye  by  relieving  the  ciliary  muscle  from  excessive 
work. 


FIG.  529. — Diagram  showing — 1,  normal  (emmetropic")  eye  bringing  parallel  rays  exactly  to  a  focus  on 
the  retina ;  2,  normal  eye  adapted  to  a  near-point ;  without  accommodation  the  rays  would  be 
focussed  behind  the  retina,  but  by  increasing  the  curvature  of  the  anterior  surface  of  the  lens 
(shown  by  a  dotted  line)  the  rays  are  focussed  on  the  retina  (as  indicated  by  the  meeting  of  the  two 
dotted  lines) ;  3,  hypermetropic  eye ;  in  this  case  the  axis  of  the  eye  is  shorter  than  normal ;  parallel 
rays  are  focussed  behind  the  retina ;  4,  myopic  eye  ;  in  this  case  the  axis  of  the  eye  is  abnormally 
long ;  parallel  rays  are  focussed  in  front  of  the  retina.  The  figure  incorrectly  represents  the 
refraction  as  occurring  only  in  the  crystalline  lens ;  the  principal  refraction  really  occurs  at  the 
anterior  surface  of  the  cornea. 


3.  Astigmatism. — This  defect,  which  was  first  discovered  by 
Airy,  is  due  to  a  greater  curvature  of  the  eye  in  one  meridian  than 
in  others.  The  eye  may  be  even  myopic  in  one  plane,  and  hyper- 
metropic in  others.  Thus  vertical  and  horizontal  lines  crossing  each 
other  cannot  both  be  focussed  at  once;  one  set  stand  out  clearly, 
and  the  others  are  blurred  and  indistinct.  This  defect,  which  is 
present  in  a  slight  degree  in  all  eyes,  is  generally  seated  in 
the  cornea,  but  occasionally  in  the  lens  as  well;  it  may  be 


836  THE   EYE   AND    VISION  JCH.  LVIII. 

corrected   by   the   use   of   cylindrical  glasses  (i.e.,  curved  only  in 
one  direction). 

4.  Spherical  Aberration. — The  rays  of   a  cone  of  light   from  an 
object  situated  at  the  side  of  the  field  of  vision  do  not  meet  all  in 
the  same  point,  owing  to  their  unequal  refraction ;  for  the  refraction 
of  the   rays   which   pass   through   the   circumference  of   a   lens  is 
greater   than   that   of  those   traversing  its   central   portion.     This 
defect  is  known  as  spherical  aberration,  and  in  the  camera,  telescope, 
microscope,  and  other   optical   instruments,  it  is   remedied  by  the 
interposition  of  a  screen  with  a  circular  aperture  in  the  path  of  the 
rays  of  light,  cutting  off  all  the  marginal  rays,  and  only  allowing  the 
passage  of  those  near  the  centre.     Such  correction  is  effected  in  the 
eye  by  the  iris,  which  prevents  the  rays  from  passing  through  any 
part  of  the  refractive  apparatus  but  its  centre.     The  image  of  an 
object  will  be  most  defined  and  distinct  when  the  pupil  is  narrow, 
the  object  at  the  proper  distance  for  vision,  and  the  light  abundant ; 
so  that,  while  a  sufficient  number  of  rays  are  admitted,  the  narrow- 
ness of  the  pupil  may  prevent  the  production  of  indistinctness  of 
the  image  by  spherical  aberration. 

Distinctness  of  vision  is  further  secured  by  the  pigment  of  the 
outer  surface  of  the  retina,  the  posterior  surface  of  the  iris  and  the 
ciliary  processes,  which  absorbs  most  of  the  light  which  is  reflected 
within  the  eye,  and  prevents  its  being  thrown  again  upon  the  retina 
so  as  to  interfere  with  the  images  there  formed. 

5.  Chromatic  Aberration. — In  the   passage  of   light   through  an 
ordinary  convex  lens,  decomposition  of  each  ray  into  its  elementary 
colours  commonly  ensues,  and  a   coloured  margin   appears  around 
the  image,  owing  to  the  unequal   refraction  which  the  elementary 
colours   undergo.     In   optical    instruments   this,   which  is   termed 
chromatic  aberration,  is  corrected  by  the  use  of  two  or  more  lenses, 
differing  in   shape   and  density,  the  second   of  which  continues  or 
increases  the  refraction  of  the  rays  produced  by  the  first,  but  by 
recombining  the  individual  parts  of  each  ray  into  its  original  white 
light,  corrects  any  chromatic   aberration  which  may  have  resulted 
from  the  first.     It  is  probable  that  the  unequal  ^refractive  power  of 
the  transparent  media  in  front  of  the  retina  may  be  the  means  by 
which  the  eye  is  enabled  to  guard  against  the  effect  of  chromatic 
aberration.     The  human  eye  is  achromatic,  however,  only  so  long  as 
the  image  is  received  at  its  focal  distance  upon  the  retina,  or  so 
long  as  the  eye  is   properly  accommodated.     If   these   conditions 
are  interfered  with,  a  more  or  less  distinct  appearance  of  colours  is 
produced. 

From  the  insufficient  adjustment  of  the  image  of  a  small  white 
object,  it  appears  surrounded  by  a  sort  of  halo  or  fringe.  This 
phenomenon  is  termed  Irradiation.  It  is  partly  for  this  reason  that 


CH.  LVI1I.]  SKIASCOPY  831 

a  white  square  on  a  black  ground  appears  larger  than  a  black  square 
of  the  same  size  on  a  white  ground.  The  phenomenon  is  naturally 
more  marked  when  the  white  object  is  a  little  out  of  focus. 

6.  Defective  Accommodation — Presbyopia. — This  condition  is  due  to 
the  gradual  loss  of  the  power  of  accommodation  which  is  an  early 
sign  of  advancing  years.  In  consequence,  the  person  is  obliged  in 
reading  to  hold  the  book  further  and  further  away  in  order  to  focus 
the  letters,  till  at  last  the  letters  are  held  too  far  for  distinct  vision. 
The  defect  is  remedied  by  weak  convex  glasses.  It  is  due  chiefly  to 
the  gradual  increase  in  density  of  the  lens,  which  is  unable  to  swell 
out  and  become  convex  when  near  objects  are  looked  at,  and  also  to 
a  weakening  of  the  ciliary  muscle,  and  a  general  loss  of  elasticity  in 
the  parts  concerned  in  the  mechanism. 

The  Skiascope  or  Retinoscope. 

The  refractive  power  of  a  lens  is  expressed  in  terms  of  its 
principal  focal  distance;  if  this  is  1  metre,  it  is  said  to  have  the 
refractive  power  of  1  diopter  (1  D.) ;  a  lens  2  D.  has  a  focal  length  of 
J  a  metre,  and  a  lens  J  D.  has  a  focal  length  of  2  metres,  and  so  on. 
The  lenses  necessary  for  correcting  errors  of  refraction  in  an  eye  are 
best  determined  by  a  simple  instrument  called  a  retinoscope ;  this  is  a 
small  circular  plane  mirror,  perforated  by  a  hole  in  the  centre 
through  which  the  observer  looks.  If  one  reflects  a  spot  of  light 
from  this  on  to  a  flat  surface,  any  movement  of  the  mirror  produces 
a  movement  of  the  spot  of  light  in  the  same  direction ;  if  the  surface 
selected,  however,  is  the  eye  of  another  person,  the  direction  of 
movement  of  the  illuminated  spot  on  the  retina  may  or  may  not  be 
the  same  as  that  in  which  the  mirror  is  moved,  according  as  whether 
the  observed  eye  is  normal,  hypermetropic,  or  myopic.  If  the 
observed  eye  is  just  a  metre  away  from  the  observer,  and  is 
emrnetropic,  then  as  the  mirror  is  tilted  from  side  to  side  the  spot 
moves  in  the  same  direction.  If  a  convex  lens  is  placed  in  a 
spectacle  frame  in  front  of  the  observed  eye,  the  parallel  rays  which 
emerge  from  the  retina  are  brought  to  a  focus  and  cross  before 
reaching  the  eye  of  the  observer.  Then  the  spot  will  move  in  the 
opposite  direction  to  the  mirror.  A  lens  of  less  than  1  D.  will  not, 
however,  accomplish  this  reversal ;  a  lens  of  more  than  1  D.  will. 
So  that  a  lens  of  1  D.  marks  the  exact  point  of  reversal.  If  the 
observed  eye  is  hypermetropic,  the  movement  of  the  spot  of  light  is 
also  with  the  mirror,  but  stronger  lenses  than  1  D.  must  be  intro- 
duced to  get  the  point  of  reversal.  If  the  lens  in  any  particular 
case  necessary  for  this  purpose  is  5  D.,  then  spectacles  of  4  D.  must 
be  ordered  for  the  patient ;  for  one  always  has  to  subtract  1  D.,  since 
that  is  required  to  get  reversal  with  the  normal  eye. 


832  THE  EYE  AND   VISION  [CH.  LVIIL 

When  the  spot  of  light  moves  against  the  mirror's  movements 
from  the  first,  then  the  observed  eye  is  myopic,  and  the  myopia  is 
greater  than  1  D.  The  "  point  of  reversal "  is  determined  by  intro- 
ducing concave  lenses  of  increasing  strength  into  the  spectacle  frame, 
until  the  spot  moves  in  the  same  direction  as  the  mirror,  and  the 
spectacles  ordered  must  have  the  value  of  the  lens  which  accomplishes 
the  reversal  plus  1  D.  to  allow  as  before  for  the  normal  eye. 

Many  people  have  differences  in  the  refractive  error  of  their  two 
eyes ;  so  each  should  be  tested  separately.  If  the  observed  eye  is 
astigmatic,  the  observations  are  more  complicated,  and  must  be  made 
in  the  different  meridians  of  the  eye,  and  the  point  of  reversal 
determined  in  each  meridian  by  means  of  suitable  cylindrical  lenses. 

FUNCTIONS  OF  THE  IRIS 

The  iris  has  the  following  two  uses : — 

1.  To  act  as  a  diaphragm  in  order  to  lessen  spherical  aberration 
in  the  manner  just  described.     This  is  specially  necessary  when  one 
wishes  to  obtain  a  clearly   defined  image  of  an  object;  the  pupil 
therefore   contracts   when  accommodation   for  a  near  object   takes 
place. 

2.  To  regulate  the  amount  of  light  entering  the  eye.     In  a  bright 
light  the  pupil  contracts ;  in  a  dim  light  it  enlarges.     This  may  be 
perfectly  well  seen  in  one's  own  iris  by  looking  at  it  in  a  mirror 
while  one  alternately  turns  a  gas-light  up  and  down. 

The  muscular  fibres  (unstriped  in  mammals,  striped  in  birds)  of 
the  iris  are  arranged  circularly  around  the  margin  of  the  pupil,  and 
radiatingly  from  its  margin.  The  radiating  fibres  are  best  seen  in 
the  eyes  of  birds  and  otters;  some  look  upon  them  as  elastic  in 
nature,  but  there  is  little  doubt  that  they  are  contractile.  Those 
who  believe  they  are  not  contractile  explain  dilatation  of  the  pupil 
as  due  to  inhibition  of  the  circular  fibres.  But  if  the  iris  is  stimu- 
lated near  its  outer  margin  at  three  different  points  simultaneously 
the  pupil  assumes  a  triangular  shape,  the  angles  of  the  triangle 
corresponding  to  the  points  stimulated ;  this  must  be  due  to  con- 
traction of  three  strands  of  the  radiating  muscle ;  inhibition  of  the 
circular  fibres  would  occur  equally  all  round. 

The  iris  is  supplied  by  three  sets  of  nerve-fibres  contained  in 
the  ciliary  nerves. 

(a)  The  third  nerve  via  the  ciliary  ganglion  and  short  ciliary 
nerves  supplies  the  circular  fibres  (fig.  530). 

(&)  The  cervical  sympathetic  supplies  the  radiating  fibres.  The 
cilio-spinal  centre  which  governs  them  is  in  the  cervical  region  of 
the  cord  (see  p.  721).  The  fibres  leave  the  cord  by  the  anterior 
root  of  the  second  thoracic  nerve,  pass  into  the  cervical  sympathetic, 


CH.  LVIIL] 


KERVES   OF  THE   IRIS 


833 


and  reach  the  eyeball  via  the  ophthalmic  branch  of  the  fifth,  and 
long  ciliary  nerves  (fig.  530). 

(c)  Fibres  of  the  fifth  nerve  which  are  sensory. 


I  MID-BRAIN 


FIG.  530.— Diagram  of  the  motor  nerves  of  the  iris.  Around  the  upper  half 
of  the  pupil  the  circular  fibres  (C)  only  are  indicated.  These  are  sup- 
plied by  the  third  nerve,  one  fibre  of  which  (III.)  is  seen  issuing  from  the 
mid-brain ;  the  cell-station  for  these  fibres  is  in  the  ciliary  ganglion  (C.G.). 
Around  the  lower  half  of  the  pupil,  the  radiating  fibres  (R)  are  indicated ; 
these  are  supplied  by  the  cervical  sympathetic  (Sy),  one  fibre  of  which  is 
shown  with  its  cell-station  in  the  superior  cervical  ganglion  (S.C.G.). 
(After  Dixon.) 

The  experiments  on  the  motor  nerves  are  those  of  section  and 
stimulation  of  the  peripheral  ends ;  the  usual  experiments  by  which 
the  functions  of  such  nerves  are  discovered. 


Nerve. 

Experiment. 

Effect  on  pupil. 

Third 
Third 
Sympathetic 
Sympathetic 

Both  nerves  together 

Section  . 
Stimulation     . 
Section  . 
Stimulation     . 

Stimulation 

Dilatation. 
Contraction. 
Contraction. 
Dilatation. 
Contraction  overcomes 
the  dilatation. 

Certain  drugs  dilate  the  pupil.  These  are  called  mydriatics ; 
atropine  is  a  well-known  example.  Others  cause  the  pupil  to 
contract.  These  are  called  myotics ;  physostigmine  and  opium 
(taken  internally)  are  instances.  Different  myotics  and  mydriatics 
act  in  different  ways,  some  exerting  their  activity  on  the  muscular, 
and  others  on  the  nervous  structures  of  the  iris. 

Reflex  actions  of  the  iris. — When  the  iris  contracts  'under  the 
influence  of  light,  the  sensory  nerve  is  the  optic,  and  the  motor  the 
third  nerve.  The  central  connection  of  the  two  nerves  in  the 
region  of  the  mid-brain  we  shall  see  later  on.  The  iris  also  contracts 
on  accommodation ;  and  the  reflex  path  concerned  in  this  action  is  a 
different  one  from  that  concerned  in  the  light  reflex,  as  this  reflex 

3G 


834  THE   EYE   AND    VISION  [CH.  LVII1. 

often  remains,  in  cases  of  locomotor  ataxy,  after  there  is  an  entire 
loss  of  the  reflex  to  light  (Argyll-Kobertson  pupil). 

On  painful  stimulation  of  any  part  of  the  body,  there  is  reflex 
dilatation  of  the  pupil.  This  is  accompanied  by  starting  of  the 
eyeballs,  due  to  contraction  of  the  plain  muscle  in  the  capsule  of 
Tenon,  which,  like  the  dilator  fibres  of  the  iris,  is  supplied  by  the 
cervical  sympathetic  nerve. 

We  may  sum  up  the  principal  conditions  under  which  the  pupil 
contracts  and  dilates,  in  the  following  table : — 

Causes  of — 

Contraction  of  the  Pupil.  Dilatation  of  the  Pupil. 

1.  Stimulation  of  third  nerve.  1.   Paralysis  of  the  third  nerve. 

2.  Paralysis  of  cervical  sympathetic.       2.  Stimulation  of  the  cervical  sympa- 

3.  When  the  eye  is  exposed  to  light.  thetic. 


4.  When  accommodation  occurs. 

5.  Under    the    local     influence    of 


physostigmine. 

6.  Under  the  influence  of  opium. 

7.  During  sleep. 


3.  In  the  dark. 

4.  When     the     accommodation     is 

relaxed. 

5.  Under  the  local  influence  of  atro- 

pine.     This  drug  also  paralyses 
the  ciliary  muscle. 

6.  In  the  last  stage  of  asphyxia. 

7.  In  deep  chloroform  narcosis. 

8.  Under   the   influence   of   certain 

emotions,  such  as  fear. 

9.  During  pain. 

There  is  a  close  connection  of  the  centres  that  govern  the  activity 
of  the  two  irides.  If  one  eye  is  shaded  by  the  hand,  its  pupil  will 
of  course  dilate,  but  the  pupil  of  the  other  eye  will  also  dilate. 
The  two  pupils  always  contract  or  dilate  together  unless  the  cause 
is  the  local  injury  to  the  nerves  of  one  side  or  the  local  action  of 
drugs. 

FUNCTIONS  OF  THE  KETINA 

The  Eetina  is  the  nervous  coat  of  the  eye ;  it  contains  the  layer 
of  nerve-epithelium  (rods  and  cones)  which  is  capable  of  receiving 
the  stimulus  of  light,  and  transforming  it  into  a  nervous  impulse 
which  passes  to  the  brain  by  the  optic  nerve. 

The  bacillary  layer,  or  layer  of  rods  and  cones,  is  at  the  back 
of  all  the  other  retinal  layers,  which  the  light  has  to  penetrate 
before  it  can  affect  this  layer.  The  proofs  of  the  statement  that  this 
is  the  layer  of  the  retina  which  is  capable  of  stimulation  by  light  are 
the  following : — 

(1)  The  point  of  exit  of  the  optic  nerve  from  the  retina, 
where  the  rods  and  cones  are  absent,  is  insensitive  to  light,  and  is 
called  the  Uind  spot.  This  is  readily  demonstrated  by  what  is  known 
as  Mariotte's  experiment.  If  we  direct  one  eye,  the  other  being 


CH.  LV1II.]  FUNCTIONS   OF   THE   RETINA  835 

closed,  upon  a  point  at  such  a  distance  to  the  side  of  any  object, 
that  the  image  of  the  latter  must  fall  upon  the  retina  at  the  point  of 
entrance  of  the  optic  nerve,  this  image  is  lost.  If,  for  example,  we 
close  the  left  eye,  and  look  steadily  with  the  right  eye  at  the  dot 


here  represented,  while  the  page  is  held  about  six  inches  from  the 
eye,  both  dot  and  cross  are  visible.  On  gradually  increasing  the 
distance  between  the  page  and  the  eye,  still  keeping  the  right  eye 
steadily  on  the  dot,  it  will  be  found  that  suddenly  the  cross  dis- 
appears from  view,  because  its  image  has  fallen  on  the  blind  spot ; 
on  removing  the  book  still  farther,  it  comes  in  sight  again.  The 
question  has  arisen  why  we  are  not  normally  conscious  of  a  gap  in 
the  image.  We  can  only  say  that  owing  to  the  spot  being  blind  from 
birth  onwards  we  have  come  to  neglect  its  blindness,  and  to  interpret 
our  experience  as  if  the  blind  spot  always  gave  rise  to  the  same 
visual  sensations  as  are  evoked  by  the  neighbouring  retinal  regions. 

(2)  In  the  fovea  centralis  which  contains  the  bacillary  layer, 
but  in  which  the  other  layers  of  the  retina  are  thinned  down  to  a 
minimum,  light  produces  the  greatest  effect.     In  the  macula  lutea, 
cones  occur  in  large   numbers,  and  in  the  fovea   centralis   cones 
without  rods  are  found,  whereas,  in  the  rest  of  the  retina  which  is 
not  so  sensitive  to  light,  there  are  fewer  cones  than  rods. 

(3)  If  a  small  lighted  candle  is  moved  to  and  fro  at  the  side  of 
and  close  to  one  eye  in  a  darkened  room,  while  the  eyes  look  steadily 
forward  on  to  a  dull  background,  a  remarkable  branching  figure 
(Purkinje's  figures)  is  seen  floating  before  the  eye,  consisting  of  dark 
lines  on  a  reddish  ground.     As  the  candle  moves,  the  figure  moves 
in  the  opposite  direction,  and  from  its  whole  appearance  there  can 
be  no  doubt  that  it  is  a  reversed  picture  of  the  retinal  vessels  pro- 
jected  before   the   eye.*     This   remarkable   appearance   is   due  to 
shadows  of  the  retinal  vessels  cast  by  the  candle;  and  it  is  only 
when   they   are  thrown   upon   the   retina   in  an    unusual  slanting 
direction  that  they  are  perceived.     The  branches  of  these  vessels  are 
distributed  in  the  nerve-fibre  and  ganglionic  layers ;  and  since  the 
light  of  the  candle  falls  on  the  retinal  vessels  from  in  front,  the 
shadow  is  cast  behind  them,  and  hence  those  elements  of  the  retina 
which  perceive  the  shadows  must  also  lie  behind  the  vessels.     Here, 
then,  we  have  a  clear  proof  that  the  light-perceiving  elements  are 
not  the  inner,  but  one  of  the  external  layers  of  the  retina ;  further 
than  this,  calculation  has  shown  it  is  the  layer  of  rods  and  cones. 
The  data  for  such  a  calculation  are — the  dimensions  of  the  eyeball, 

*  Purkinje's  figures  can  be  much  more  readily  seen  by  simply  looking  steadily 
down  a  microscope,  and  moving  the  whole  instrument  backwards  and  forwards,  o'r 
from  side  to  side,  while  so  doing. 


836  THE   EYE  AND   VISION  [CH.  LVI1I. 

the  distance  of  the  screen  from  the  eye,  the  angle  through  which  the 
candle  is  moved,  and  the  displacement  of  the  figure  seen. 

Duration  of  Visual  Sensations. — The  duration  of  the  sensation 
produced  by  a  luminous  impression  on  the  retina  is  always  greater 
than  that  of  the  impression  which  produces  it.  However  brief  the 
luminous  impression,  the  effect  on  the  retina  always  lasts  for  about 
one-eighth  of  a  second.  Thus,  supposing  an  object  in  motion,  say  a 
horse,  to  be  revealed  on  a  dark  night  by  a  flash  of  lightning.  The 
object  would  be  seen  apparently  for  an  eighth  of  a  second,  but  it 
would  not  appear  in  motion ;  because,  although  the  image  remained 
on  the  retina  for  this  time,  it  was  really  revealed  for  such  an 
extremely  short  period  (a  flash  of  lightning  lasting  only  a  millionth 
of  a  second)  that  no  appreciable  movement  on  the  part  of  the  object 
could  have  taken  place  in  the  period  during  which  it  was  revealed  to 
the  retina  of  the  observer.  The  same  fact  is  proved  in  a  reverse 
way.  The  spokes  of  a  rapidly  revolving  wheel  are  not  seen  as 
distinct  objects,  because  at  every  point  of  the  field  of  vision  over 
which  the  revolving  spokes  pass,  a  given  impression  has  not  faded 
before  another  replaces  it.  Thus  every  part  of  the  interior  of  the 
wheel  appears  occupied. 

The  stimuli  which  excite  the  retina  are  exceedingly  slight ;  for  instance,  the 
minimum  stimulus  in  the  form  of  green  light  is  equal  in  terms  of  work  to  that  which 
is  done  in  raising  a  ten-millionth  part  of  a  milligramme  to  the  height  of  a  millimetre, 
and  even  some  of  this  is  doubtless  wasted  in  the  form  of  heat.  The  time  during 
which  the  stimulus  acts  may  be  excessively  small ;  thus  light  from  a  rapidly  rotating 
mirror  is  visible  even  when  it  only  falls  upon  the  retina  for  one  eight-millionth  part 
of  a  second.  Some  physiologists  have  drawn  an  analogy  between  retinal  and 
muscular  excitations.  There  is  no  complete  analogy,  but  the  following  points  of 
resemblance  may  be  noted : — 

1.  The  retina  like  the  muscle  possesses  a  store  of  potential  energy,  which  the 
stimulus  serves  to  fire  off. 

2.  Fatigue  on  action,  and  recovery  after  rest  are  noticeable  in  both. 

3.  The  curve  of  retinal  excitation,  like  the  muscle  curve,  rises  not  abruptly  but 
gradually  to  its  full  height,  and  on  the  cessation  of  the  stimulus  takes  a  measurable 
time  to  fall  again,  the  retinal  impression  outlasting  the  stimulus  by  about  one-eighth 
of  a  second. 

4.  With  comparatively  slow  intermittent  excitation,  the  phenomenon  known  as 
flicker  takes  place ;  this  may  be  shown  by  the  slow  rotation  on  Maxwell's  machine 
of  a  disc  painted  with  alternate  black  and  white  sectors.     This  roughly  corresponds 
with  what  in  a  muscle  is  called  incomplete  tetanus. 

5.  When  the  rate  of  stimulation  is  increased,  as  by  increasing  the  speed  of  rota- 
tion of  the  disc  just  alluded  to  (say  to  twenty  or  thirty  times  a  second)  the  resulting 
sensation  is  a  smooth  one  of  greyness.     This  fusion  of  individual  stimuli  into  a  con- 
tinuous sensation  does  not  by  any  means  correspond  to  the  complete  tetanus  of 
muscle,  for  the  resultant  sensation  has  a  brightness  corresponding  not  to  a  summa- 
tion of  the  individual  fusing  sensations,  but  to  a  brightness  which  would  ensue  if  the 
stimuli  were  spread  evenly  over  the  surface  of  the  disc  (Talbot's  Law). 

The  Ophthalmoscope. 

Every  one  is  perfectly  familiar  with  the  fact,  that  it  is  quite  im- 
possible to  see  thefundus  or  back  of  another  person's  eye  by  simply 


CH.  LVITI.]  THE   OPHTHALMOSCOPE  837 

looking  into  it.  The  interior  of  the  eye  forms  a  perfectly  black 
background.*  The  same  remark  applies  to  the  difficulty  we  experi- 
ence in  seeing  into  a  room  from  the  street  through  the  window  unless 
the  room  is  lighted  within.  In  the  case  of  the  eye  this  fact  is  partly 
due  to  the  feebleness  of  the  light  reflected  from  the  retina,  most  of  it 
being  absorbed  by  the  retinal  pigment ;  but  far  more  to  the  fact  that 
every  such  ray  is  reflected  straight  to  the  source  of  light  (e.g. 
candle),  and  cannot,  therefore,  be  seen  by  the  unaided  eye  without 
intercepting  the  incident  light  from  the  candle,  as  well  as  the 
reflected  rays  from  the  retina.  This  difficulty  is  surmounted  by  the 
use  of  the  ophthalmoscope. 

The  ophthalmoscope  was  invented  by  Helmholtz ;  as  a  mirror  for 
reflecting  the  light  into  the  eye,  he  employed  a  bundle  of  thin  glass 
plates;  this  mirror  was  transparent,  and  so  he  was  able  to  look 
through  it  in  the  same  direction  as  that  of  the  rays  of  the  light  it 
reflected.  It  is  almost  impossible  to  over-estimate  the  boon  this 
instrument  has  been  to  mankind ;  previous  to  this  in  the  examina- 
tion of  cases  of  eye  disease,  the  principal  evidence  on  which  the 
surgeon  had  to  rely  was  that  derived  from  the  patient's  sensations ; 
now  he  can  look  for  himself. 

The  instrument,  however,  has  been  greatly  modified  since  Helm- 
holtz's  time ;  the  principal  modification  is  the  substitution  of  a  con- 
cave mirror  of  silvered  glass  for  the  bundle  of  glass  plates ;  this  is 
mounted  on  a  handle,  and  is  perforated  in  the  centre  by  a  small  hole 
through  which  the  observer  can  look. 

The  methods  of  examining  the  eye  with  this  instrument  are — the  direct  and  the 
indirect :  both  methods  of  investigation  should  be  employed.  A  drop  of  a  solution 
of  atropine  (two  grains  to  the  ounce)  or  of  hoffiatropine  hydrobromate,  should  be 
instilled  about  twenty  minutes  before  the  examination  is  commenced ;  the  ciliary 
muscle  is  thereby  paralysed,  the  power  of  accommodation  is  abolished,  and  the 
pupil  is  dilated.  This  will  materially  facilitate  the  examination;  but  it  is  quite 
possible  to  observe  all  the  details  to  be  presently  described  without  the  use  of  such 
drugs.  The  room  being  now  darkened,  the  observer  seats  himself  in  front  of  the 
person  whose  eye  he  is  about  to  examine,  placing  himself  upon  a  somewhat  higher 
level.  Let  us  suppose  that  the  right  eye  of  the  patient  is  being  examined.  A 
brilliant  and  steady  light  is  placed  close  to  the  left  ear  of  the  patient.  Taking  the 
mirror  in  his  right  hand,  and  looking  through  the  central  hole,  the  operator  directs 
a  beam  of  light  into  the  eye  of  the  patient.  A  red  glare,  known  as  the  reflex,  is 
seen ;  it  is  due  to  the  illumination  of  the  retina.  The  patient  is  then  told  to  look 
at  the  little  finger  of  the  observer's  right  hand  as  he  holds  the  mirror;  to  effect 
this  the  eye  is  rotated  somewhat  inwards,  and  at  the  same  time  the  reflex  changes 
from  red  to  a  lighter  colour,  owing  to  the  reflection  from  the  optic  disc.  The 

*  In  some  animals  (e.g.  the  cat),  the  pigment  is  absent  from  a  portion  of  the 
retinal  epithelium ;  this  forms  the  Tapatum  lucldum.  The  use  of  this  is  supposed  to 
be  to  increase  the  sensitiveness  of  the  retina,  the  light  being  reflected  back  through 
the  layer  of  rods  and  cones.  It  is  probably  the  case  that  these  animals  are  able  to  see 
clearly  with  less  light  than  we  can,  hence  the  popular  idea  that  a  cat  can  see  in  the 
dark.  In  fishes  a  tapetum  lucidum  is  often  present ;  here  the  brightness  is  increased 
by  crystals  of  guanine. 


838 


THE   EYE   AND   VISION 


[CH.  LVIII. 


observer  now  approximates  the  mirror,  with  his  eye  to  the  eye  of  the  patient,  taking 
care  to  keep  the  light  fixed  upon  the  pupil,  so  as  not  to  lose  the  reflex.  At 
a  certain  point,  which  varies  with  different  eyes,  but  is  usually  reached  when 

there  is  an  interval  of  about  two  or  three  inches 
between  the  observed  and  the  observing  eye,  the 
vessels  of  the  retina  become  visible.  Examine 
carefully  the  fundus  of  the  eye,  i.e.,  the  red 
surface — until  the  optic  disc  is  seen ;  trace  its 
circular  outline,  and  observe  the  small  central 
white  spot,  the  porus  opticus,  or  physiological 
pit :  near  the  centre  is  the  central  artery  of  the 
retina  breaking  up  upon  the  disc  into  branches ; 
veins  also  are  present,  and  correspond  roughly 
to  the  course  of  the  arteries.  Trace  the  vessels 
over  the  disc  on  to  the  retina.  Somewhat  to 
the  outer  side,  and  only  visible  after  some 
practice,  is  the  yellow  spot,  with  the  smaller 
lighter-coloured  fovea  centralis  in  its  centre. 
This  constitutes  the  direct  method  of  examina- 
tion ;  by  it  the  various  details  of  the  fundus  are 
seen  as  they  really  exist,  and  it  is  this  method 
which  should  be  adopted  for  ordinary  use. 

If  the  observer  is  myopic  or  hypermetropic, 
he  will  be  unable  to  employ  the  direct  method 
of  examination  until  he  has  remedied  his  de- 
fective vision  by  the  use  of  proper  glasses. 

In  the  indirect  method  the  patient  is  placed 
as  before,  and  the  operator  holds  the  mirror  in 
his  right  hand  at  a  distance  of  twelve  to  eighteen 
inches  from  the  patient's  right  eye.  At  the  same 
time  he  rests  his  left  little  finger  lightly  upon  the 
patient's  right  temple,  and  holding  a  convex  lens 
between  his  thumb  and  forefinger,  two  or  three 
inches  in  front  of  the  patient's  eye,  directs  the 
light  through  the  lens  into  the  eye.  The  red 
reflex,  and  subsequently  the  white  one,  having 
been  gained,  the  operator  slowly  moves  his 
mirror,  and  with  it  his  eye,  towards  or  away 
from  the  face  of  the  patient,  until  the  outline  of 
one  of  the  retinal  vessels  becomes  visible,  when 
very  slight  movements  on  the  part  of  the  operator  will  suffice  to  bring  into  view  the 
details  of  the  fundus  above  described,  but  the  image  will  be  much  smaller  and  in- 
verted. The  appearances  seen  are  depicted  in  fig.  516.  The  lens  should  be  kept 
fixed  at  a  distance  of  two  or  three  inches,  the  mirror  alone  being  moved  until  the 
disc  becomes  visible  :  should  the  image  of  the  mirror,  however,  obscure  the  disc,  the 
lens  may  be  slightly  tilted. 

The  two  next  figures  show  diagrammatically  the  course  of  the  rays  of  light. 
Fig.  532  represents  what  occurs  when  employing  the  direct  method.  S  is  the 
source  of  light,  and  M  M  the  concave  mirror  with  its  central  aperture,  which  reflects 
the  rays  ;  these  are  focussed  by  the  eye  E,  which  is  being  examined,  to  a  point  in  the 
vitreous  humour,  and  this  produces  a  diffuse  lighting  of  the  interior  of  the  eyeball. 
Rays  of  light  issuing  from  the  point  p  emerge  from  the  eye  parallel  to  one  another, 
and  enter  the  observer's  eye  E1 ;  they  are  brought  to  a  focus  p1  on  the  retina  as  the 
eye  is  accommodated  for  distant  vision.  Similarly  the  point  m  and  n  will  give  rise 
to  images  at  m1  and  w1  respectively. 

Fig.  533  represents  what  occurs  in  examining  the  eye  by  the  indirect  method. 

S  is  the  source  of  light,  M  M  the  mirror,  E  the  observed,  and  E1  the  observing 

eye  as  before.     The  rays  of  light  are  reflected  from  the  mirror  and  form  an  image 

at  o1 ;  they  then  diverge  and  are  again  made  convergent  by  the  lens  L  held  in  front 

of  the  eye  by  the  observer;  by  this  means  a  second  image  is  focussed  just  behind 


FIG.  531.— The  Ophthalmoscope.  The 
small  upper  mirror  is  for  direct,  the 
larger  for  indirect,  illumination. 


en.  LVIII.] 


THE   PERIMETER 


839 


the  crystalline  lens  of  the  eye  E.     They  then  again  diverge  and  diffusely  light  up 
the  interior  of  the  eyeball.     The  rays  of  light  reflected  from  two  points  i  and  m  on 


E1 


IV! 


Fio.  532.— The  course  of  the  light  in  examining  the  eye  by  the  direct  method.    (T.  G.  Brodie.) 

the  retina  diverging  from  the  eye  are  refracted  by  the  glass  lens  L,  and  give  an 
inverted  real  image  i1  ml  larger  than  the  object  i  m.     These  latter  rays  then  diverge, 


M 


Fio.  533. — The  course  of  the  light  in  examining  the  eye  by  the  indirect  method.    (T.  G.  Brodie.) 

and  are  collected  and  focussed  by  the  observing  eye  E1  to  give  an  image  i2  m'2  on  the 
retina.     (T.  G.  Brodie.) 

The  Perimeter. 

This  is  an  instrument  for  mapping  out  the  field  of  vision.  It 
consists  of  a  graduated  arc,  which  can  be  moved  into  any  position, 
and  which  when  rotated  traces  out  a  hollow  hemisphere.  In  the 
centre  of  this  the  eye  under  examination  is  placed,  the  other  eye 
being  closed.  The  examiner  then  determines  on  the  surface  of  the 
hemisphere  those  points  at  which  the  patient  just  ceases  or  just 
begins  to  see  a  small  object  moved  along  the  arc  of  the  circle.  These 
points  are  plotted  out  on  a  chart  graduated  in  degrees,  and  by  con- 
necting them  the  outline  of  the  field  of  vision  is  obtained. 

Fig.  534  shows  one  of  the  forms  of  perimeter  very  generally 
employed,  and  fig.  535  represents  one  of  the  charts  provided  with 


840 


THE   EYE    AND   VISION 


[CH.  LVI1I. 


FIG.  534.— Priestley  Smith's  Perimeter. 

0 
20 


60. 


100 


120 


140 


140 


160 


160 


180 


FIG.  535.— Perimeter  chart  for  the  right  eye. 


CH.  LVIII.]  VISUAL  SENSATIONS  841 

the  instrument.  The  blind  spot  is  shown,  and  the  dotted  line 
represents  the  normal  average  field  of  vision  for  the  right  eye.  It 
will  be  seen  that  the  field  of  vision  is  most  extensive  on  the  outer 
side ;  it  is  less  on  the  inner  side  because  of  the  presence  of  the  nose. 

By  the  use  of  the  same  instrument,  it  is  found  that  the  colour 
of  a  coloured  object  is  not  distinguishable  at  the  margin,  but  only 
towards  the  centre  of  the  field  of  vision,  but  there  are  differences 
for  different  colours;  thus  a  blue  or  yellow  object  is  seen  to  be 
blue  or  yellow  over  a  wider  field  than  a  red  or  green  object. 

In  disease  of  the  optic  nerve,  contraction  of  the  field  of  vision 
for  white  and  coloured  objects  is  found.  This  often  occurs  before 
any  change  in  the  optic  nerve  is  discoverable  by  the  ophthalmoscope. 

The  yellow  spot  of  one's  own  eye  can  be  rendered  evident  by 
what  is  called  Clerk-Maxwell's  experiment : — On  looking  through  a 
solution  of  chrome-alum  in  a  bottle  with  parallel  sides,  an  oval 
purplish  spot  is  seen  in  the  green  colour  of  the  alum.  This  is  due 
to  the  pigment  of  the  yellow  spot. 

Visual  Sensations. 

Visual  sensations  are  of  two  kinds,  colour  sensations  and  colour- 
less sensations.  Colour  sensations  differ  (1)  in  hue,  for  instance,  blue, 
red,  yellow ;  (2)  in  saturation,  for  instance,  pale  green  and  full  green ; 
this  depends  upon  the  degree  of  admixture  with  white  light ;  and  (3) 
in  intensity,  for  instance,  a  weak  sensation  or  a  strong  sensation. 
These  differences  are  in  part  dependent  respectively  on  the  length, 
the  purity,  and  the  amplitude  of  the  light- wave ;  but  they  are  also 
dependent  on  the  local  or  general  condition  of  the  cerebro-retinal 
apparatus  at  the  time  of  stimulation.  Colours  also  differ  (4)  in 
brightness  or  luminosity;  this  is  a  purely  psychological  quality 
devoid  of  any  known  physical  counterpart.  The  brightness  of  a 
colour  may  be  measured  by  determining  the  shade  of  grey  to  which 
it  appears  equivalent.  Even  the  most  saturated  colours  (for 
instance,  yellow  and  blue)  have  different  degrees  of  brightness. 
Colourless  sensations  include  the  grey  series  from  the  deepest  black 
to  the  most  blinding  white. 

If  a  ray  of  sunlight  is  allowed  to  pass  through  a  prism,  it  is 
decomposed  by  its  passage  into  rays  of  different  colours,  which  are 
called  the  colours  of  the  spectrum;  they  are  red,  orange,  yellow, 
green,  blue,  indigo,  and  violet.  The  red  rays  are  the  least  turned  out 
of  their  course  by  the  prism,  and  the  violet  the  most,  whilst  the  other 
colours  occupy  in  order  places  between  these  two  extremes.  The 
differences  in  the  colour  of  the  rays  depend  upon  the  rapidity  of 
vibrations  producing  each,  the  red  rays  being  the  least  rapid 
and  the  violet  the  most.  In  addition  to  these,  there  are  other  rays 
which  are  invisible  but  which  have  definite  properties ;  those  to  the 


842  THE   EYE   AND   VISION  [CH.  LVIII. 

left  of  the  red  are  less  refrangible,  being  the  calorific  rays  which  act 
upon  the  thermometer,  and  those  to  the  right  of  the  violet,  which 
are  called  the  actinic  rays,  have  a  powerful  chemical  action. 

White  light  may  be  built  from  its  constituents  in  several  ways, 
for  instance,  by  a  second  prism  reversing  the  dispersion  produced  by 
the  first,  or  by  causing  the  colours  of  the  spectrum  to  fall  on  the 
retina  in  rapid  succession.  The  best  way  to  study  the  effects  of 
compounding  successive  colour  stimuli  is  by  means  of  a  rapidly 
revolving  disc  to  which  two  or  more  coloured  sectors  are  fixed. 
Each  colour  is  viewed  in  rapid  succession,  but  owing  to  the  per- 
sistence of  retinal  impressions,  the  constituent  colour  stimuli  give  a 
single  sensation  of  colour. 

A  colourless  sensation  can  be  produced  by  the  mixture  of  three 
colours,  or  even  of  two  colours  in  certain  hues  and  proportions. 
These  pairs  of  colours,  of  which  red  and  greenish-blue,  orange  and 
blue,  and  violet  and  yellow  are  examples,  are  called  complementary. 

Thus  blue  and  orange,  when  rotated  on  the  colour-wheel,  produce  a  colourless 
sensation  ;  but  it  is  well  known  that  a  mixture  of  blue  and  orange  paint  gives  green. 
This  is  explained  on  the  supposition  that  the  colours  used  are  not  pure  and  that 
each  contains  green ;  the  true  blue  and  orange  present  neutralise  each  other  to 
produce  white,  and  thus  green  is  the  only  colour  sensation  obtained. 

Three  properly  chosen  colours  will  not  only  produce  a  colourless 
sensation,  but  when  combined  in  appropriate  amounts  they  can  be 
made  to  yield  any  other  colour  sensation.  It  is  on  this  principle 
that  Thomas  Young  based  his  trichromatic  theory  of  colour  vision, 
which  was  subsequently  elaborated  by  Helmholtz  and  Clerk-Maxwell. 
It  is  known  as  the  Young-Helmholtz  theory.  The  theory  selects 
red,  green,  and  violet  as  the  three  primary  colour-sensations.  These 
three  particular  colours  are  chosen,  partly  because  of  their  position 
within  the  spectrum,  partly  on  account  of  the  phenomena  of  colour- 
blindness, and  for  other  reasons. 

The  Young-Helmholtz  theory  teaches  that  there  are  in  the  retina 
certain  elements  (?  within  the  cones)  which  answer  to  each  of  these 
primary  colours,  whereas  the  innumerable  intermediate  shades  of 
colour  are  produced  by  stimulation  of  the  three  primary  colour 
terminals  in  different  degrees,  the  sensation  of  white  being  produced 
when  the  three  elements  are  equally  excited.  Thus,  if  the  retina  is 
stimulated  by  rays  of  certain  wave  length,  at  the  red  end  of  the  spec- 
trum, the  terminals  of  the  other  colours,  green  and  violet,  are  hardly 
stimulated  at  all,  but  the  red  terminals  are  strongly  stimulated, 
the  resulting  sensation  being  red.  The  orange  rays  excite  the  red 
terminals  considerably,  the  green  rather  more,  and  the  violet  slightly, 
the  resulting  sensation  being  that  of  orange,  and  so  on  (fig.  536). 

Another  theory  of  colour  vision  (Hering's)  supposes  that  there  are 
six  primary  colour-sensations,  viz. :  three  antagonistic  (complemen- 


CH.  LVITI.] 


COLOUR  VISION 


843 


FIG.  536.— Diagram  of  the  three  primary  colour- 
sensations.  (Young-Helmholtz  theory.)  1  is 
the  red ;  2,  green,  and  3,  violet,  primary 
colour-sensation.  The  lettering  indicates  the 
colours  of  the  spectrum.  The  diagram  indi- 
cates by  the  height  of  the  curve  to  what 
extent  the  several  primary  sensations  of 
colour  are  excited  by  vibrations  of  different 
wave-lengths. 


tary)  pairs,  black  and  white,  red  and  green,  and  yellow  and  blue-; 
and  that  these  are  produced  by  the  changes  either  of  disintegration 
or  of  assimilation  taking  place  in  certain  substances,  which  (the 
theory  supposes)  exist  in  the 
cerebro-retinal  apparatus.  Each 
of  the  substances  corresponding 
to  a  pair  of  colours  is  capable  of 
undergoing  two  changes,  one  of 
disintegration,  and  the  other  of 
construction,  with  the  result  of 
producing  one  or  other  colour. 
For  instance,  in  the  white-black 
substance,  when  disintegration  is 
in  excess  of  construction  or  as- 
similation, the  sensation  is  white, 
and  when  assimilation  is  in  excess 
of  disintegration  the  reverse  is 
the  case;  and  similarly  with  the 
red-green  substance,  and  with  the 

yellow-blue  substance.  When  the  repair  and  disintegration  are 
equal  with  the  first  substance,  the  visual  sensation  is  grey ;  but  in 
the  other  pairs,  when  this  is  the  case,  no  colour-sensation  occurs. 
The  rays  of  the  spectrum  to  the  red  end  produce  changes  in  the 
red-green  substance,  with  a  resulting  sensation  of  red,  whilst  the 
(orange)  rays  further  to  the  right  affect  both  the  red-green  and  the 
yellow-blue  substances ;  blue  rays  cause  constructive  changes  in  the 
yellow-blue  substances,  but  none  in  the  red-green,  and  so  on.  All 
colours  act  on  the  white-black  substance  as  well  as  on  the  red-green 
or  yellow-blue  substance. 

Neither  theory  satisfactorily  accounts  for  all  the  numerous  com- 
plicated problems  presented  in  the  physiology  of  colour  vision.  One  of 
these  problems  is  colour-blindness,  a  by  no  means  uncommon  visual 
defect.  Some  people  are  completely  colour  blind  (see  further  p.  848), 
but  the  commonest  form  is  the  inability  to  distinguish  between  red 
and  green.  Helmholtz's  explanation  of  such  a  condition  is,  that  the 
elements  of  the  retina  which  receive  the  impression  of  red  or  green 
are  absent,  or  very  imperfectly  developed,  and  Bering's  would  be  that 
the  red-green  substance  is  absent  from  the  cerebro-retinal  apparatus. 
Other  varieties  of  colour-blindness,  in  which  the  other  colour-perceiv- 
ing elements  are  absent,  have  been  shown  to  exist  occasionally. 

Bering's  theory  appears  to  meet  the  difficulty  best,  for  if  the  red 
element  of  Helmholtz  were  absent,  the  patient  ought  not  to  be  able 
to  perceive  white  sensations,  of  which  red  is  a  constituent  part; 
whereas,  according  to  Bering's  theory,  the  white-black  visual  sub- 
stance remains  intact.  These  two  theories  have  been  for  a  long  time 


844  THE   EYE   AND   VISION  [CH.  LYIII. 

before  the  scientific  world.  As  facts  have  accumulated,  it  has 
been  for  some  years  recognised  that  many  facts  could  not  be 
reconciled  with  either ;  and  modifications  of  one  or  the  other  have 
been  from  time  to  time  introduced. 

C.  J.  Burch  found  that  by  exposing  the  eye  to  bright  sunlight  in  the  focus  of  a 
burning-glass  behind  transparent  coloured  screens,  it  is  possible  to  produce 
temporary  colour  blindness.  After  red  light,  the  observer  is  for  some  minutes  red- 
blind,  scarlet  geraniums  look  black,  yellow  flowers  green,  and  purple  flowers  violet 
After  violet  light,  violet  looks  black,  purple  flowers  crimson,  and  green  foliage 
richer  than  usual.  After  light  of  other  colours,  corresponding  effects  are  produced. 
If  one  eye  is  made  purple-blind,  and  the  other  green-blind,  all  objects  are  seen  in 
their  natural  colours,  but  in  exaggerated  perspective,  due  to  the  difficulty  the  brain 
experiences  in  combining  the  images  from  the  two  eyes. 

By  using  a  brightly-illuminated  spectrum,  and  directing  the  eye  to  certain  of  its 
colours,  the  eye  in  time  becomes  fatigued  and  blind  for  that  colour,  so  that  it  is  no 
longer  seen  in  the  spectrum.  Thus,  after  green  blindness  is  induced  the  red 
appears  to  meet  the  blue,  and  no  green  is  seen.  If,  however,  the  eye  is  exposed  to 
yellow  light,  it  does  not  similarly  become  blind  for  yellow  only,  but  for  red  and 
green  too.  This  supports  the  Young-Helmholtz  theory,  that  the  sensation  yellow 
is  one  compounded  of  the  red  and  green  sensations.  By  an  exhaustive  examination 
of  the  different  parts  of  the  spectrum,  in  this  way  it  thus  becomes  possible  to 
differentiate  between  the  primary  colour-sensations  and  those  which  are  compound. 
By  a  study  of  this  kind,  Burch  concludes  that  the  phenomena  of  colour  vision  are 
in  accordance  with  the  Young-Helmholtz  theory,  with  the  important  addition  that 
there  is  a  fourth  primary  colour-sensation,  namely,  blue.  He  could  not  discover 
that  colour-sensations  are  related  to  each  other  in  the  sense  indicated  by  Hering. 
Each  may  be  exhausted  without  either  weakening  or  strengthening  the  others. 
These  observations  were  confirmed  by  examining  in  a  similar  way  the  colour- 
sensations  of  seventy  other  people,  but  there  are  individual  differences  in  the 
extent  to  which  the  colour-sensations  overlap. 

Testing  for  Colour-blindness. — The  test  formerly  adopted  by  the 
Board  of  Trade  consists  in  matching  skeins  of  wool  from  a  heap  of 
skeins  of  different  colours  (Holmgren's  worsteds).  It  has,  however, 
been  shown  that  the  test  is  not  trustworthy,  and  it  has  been  supple- 
mented by  one  in  which  the  subject  is  required  to  name  the  colours  of 
lights  in  a  lantern.  The  Edridge-Green  lantern  is  one  of  the  best  to 
employ ;  in  it  the  intensity  and  colour  of  the  light  and  the  order  in 
which  the  colours  are  shown  can  be  easily  varied.  If  the  colour- 
blind person  is  made  to  examine  and  report  on  the  colours  of  a 
spectrum,  or  in  portions  of  the  spectrum  exposed  to  view,  the  results 
obtained  are  more  accurate,  but  this  is  not  so  simple  as  the  lantern 
test. 

After-Images. — These  are  the  after-effects  of  retinal  excitation, 
and  are  divided  into  positive  and  negative.  Positive  after-images 
resemble  the  original  image  in  distribution  of  brightness  and 
colour.  In  negative  after-images  bright  parts  appear  dark,  dark 
parts  bright,  and  coloured  parts  in  the  complementary  colours. 

If  a  bright  white  object  is  looked  at,  and  the  eyelids  are  then 
closed,  a  positive  after-image  is  seen  which  fades  gradually,  but  as  it 
fades  it  passes  through  blue,  violet  or  red,  to  orange ;  according  to 


I. 


II. 


III.  IV. 

Plate  to  illustrate  simultaneous  and  successive  contrast. 
For  explanation  see  text. 


CH.  LVIII.]        SIMULTANEOUS   AND   SUCCESSIVE   CONTRAST  845 

the  Young-Helmholtz  theory,  this  is  explained  on  the  hypothesis 
that  the  excitation  does  not  decline  with  equal  rapidity  in  the  three 
colour  terminals.  A  positive  after-image  is  readily  obtained  by 
momentarily  looking  at  a  bright  object,  e.g.  a  window,  after  waking 
from  sleep.  Negative  after-images  may  be  seen  either  by  closing 
the  eyes  or  by  turning  them  to  a  uniform  grey  surface  after  viewing 
an  object  steadily.  If  the  object  looked  at  is  coloured,  the  negative 
after-image  seen  upon  such  a  background  is  in  its  complementary 
colour;  this  is  explained  by  the  Young-Helmholtz  theory,  on  the 
supposition  that  the  colour-perceiving  element  for  the  colour  looked 
at  is  the  most  fatigued,  and  the  terminals  for  its  complementary 
colour  least  fatigued.  On  the  Hering  theory,  one  colour  produces 
anabolic  or  katabolic  effects  as  the  case  may  be ;  on  withdrawing  the 
eye  from  stimulation  by  that  particular  colour,  the  opposite  phase  of 
metabolism  takes  place  and  produces  the  complementary  colour. 

Simultaneous  and  Successive  Contrast. — Negative  after-images  are 
frequently  spoken  of  as  phenomena  of  successive  contrast.  The 
phenomena  of  simultaneous  contrast  are  well  illustrated  by  the 
four  figures  of  the  accompanying  Plate.  In  all  these  figures  the 
oblong  grey  strip  is  actually  of  the  same  brightness.  This  can  easily 
be  proved  by  screening  from  view  the  surrounding  parts  of  the 
figures,  which  cause  the  greys  to  appear  different.  The  grey  in  I. 
appears  darker  than  that  in  II.,  while  the  grey  in  III.  appears 
yellowish  and  in  IV.  reddish.  If  these  effects  are  not  sufficiently 
obvious,  they  immediately  become  so  when  the  entire  surface  is 
covered  over  with  a  sheet  of  thin  tissue  paper. 

Figs.  I.  and  II.  are  examples  of  brightness  contrast ;  Figs.  III.  and 
IV.  of  -colour  contrast.  The  effects  of  these  two  varieties  of 
simultaneous  contrast  may  be  stated  thus :  a  given  grey  object  looks 
darker  when  viewed  against  a  bright  background  than  when  viewed 
against  a  dark  background ;  when  the  background  is  coloured,  it  is 
tinged  with  the  complementary  colour  of  the  former. 

Helmholtz  attributed  the  effects  of  simultaneous  contrast  to 
errors  of  judgment,  and  not  to  altered  conditions  of  the  retinal 
apparatus.*  But  there  can  be  no  doubt  that  simultaneous  contrast 
has  as  simple  a  sensory  origin  as  successive  contrast  (negative  after- 
images). For  if  either  of  the  two  lower  figures  of  the  plate  is  care- 
fully fixated  for  about  a  minute  (fixation  of  the  central  dot  will 
help  to  prevent  involuntary  movements  of  the  eyes),  and  if  the 
gaze  be  then  transferred  to  a  spot  on  a  sheet  of  white  or  grey  paper, 
not  only  will  the  outer  squares  appear  in  their  complementary 
colour,  but  also  the  grey  strips  will  appear  tinged,  now  likewise  in  a 

*  By  "retina"  here  and  elsewhere  we  mean  " cerebro-retinal  apparatus."  We 
have  no  knowledge  of  the  precise  share  of  retina  and  brain  in  the  development  of 
visual  sensations  and  after-sensations. 


846  THE   EYE   AND    VISION  [CH.  LVIlL 

complementary  colour.  So,  too,  if  a  point  midway  between  Figs.  I. 
and  II.  is  fixated,  and  the  plate  held  at  a  sufficient  distance  for 
both  figures  to  be  simultaneously  visible,  the  after-image  of  the  grey 
strip  of  II.  will  appear  darker  than  that  of  I. 

Seeing  that  simultaneous  contrast  persists  in  after-images,  and 
seeing  how  generally  recognised  are  its  effects  (for  instance,  by  the 
painter,  who  depicts  in  Hue  the  shadows  cast  by  an  object  on  the  yellow 
sand),  it  seems  far  more  probable  that  the  part  played  by  the  higher 
mental  processes  consists,  not,  as  Helmholtz  supposed,  in  causing  the 
illusion,  but  in  reducing  or  overcoming  it.  According  to  this  view, 
experience  educates  us  in  seeing  objects  in  what  we  know  to  be 
their  real  colour,  instead  of  in  the  colour  which  would  result  from  the 
operation  of  simultaneous  contrast.  Some  support  is  lent  to  this 
view  by  the  fact  that  contrast  is  much  enhanced  when  all  irregu- 
larities are,  as  far  as  possible,  eliminated  from  the  surface  of  the 
object  (here,  the  grey  oblong)  in  which  the  contrast  colour  is 
induced,  or  when  that  object  is  made  to  appear,  e.g.  by  covering  the 
whole  with  tissue  paper  to  combine  with  the  object  (the  coloured 
square)  which  induces  the  contrast  colour,  so  as  to  form  an  apparently 
single  object.  On  the  other  hand,  colour  contrast  is  very  markedly 
reduced,  if  the  grey  object  is  outlined  in  pencil  on  the  tissue  paper 
through  which  it  is  viewed.  Thus,  whatever  tends  to  the  apparent 
independence  of  the  object  in  which  the  contrasting  colour  is  induced 
tends  to  the  reduction  of  the  contrast  effect. 

Insisting  on  the  sensory  nature  of  simultaneous  contrast,  Hering 
explained  it  in  the  following  way.  He  supposed  that  excitation 
of  an  area  of  the  retina  by  a  stimulus  of  given  colour  or  brightness 
simultaneously  induces  an  opposite  metabolic  process  in  the  same 
colour  apparatus  in  neighbouring  areas  of  the  retina.  When,  for 
example,  a  part  of  the  retina  is  being  stimulated  by  blue,  the 
anabolic  change  thus  evoked  in  the  yellow-blue  apparatus  simultane- 
ously is  supposed  to  induce  a  katabolic  change  in  the  same  apparatus 
in  the  neighbouring  retinal  area  which  is  being  excited  by  a  grey 
stimulus.  Consequently,  the  grey  acquires  a  yellowish  tinge. 

Binocular  colour-mixture. — By  means  of  the  stereoscope,  binocular 
combinations  of  colour  can  be  obtained.  Thus,  if  one  eye  is  exposed 
to  a  red  disc,  and  the  corresponding  portion  of  the  other  eye  to  a 
yellow  one,  the  mind  usually  perceives  one  disc  of  an  orange  tint ; 
but  frequently,  especially  if  there  be  differences  of  brightness  or  of 
form  in  the  two  objects,  we  notice  that  "rivalry  of  the  fields  of 
vision  "  occurs,  first  one  then  the  other  disc  rising  into  consciousness. 
A  stereoscopic  combination  of  black  and  white  produces  the  appear- 
ance of  metallic  lustre ;  this  is  very  beautifully  shown  with  figures  of 
crystals,  one  black  on  a  white  ground,  the  other  white  on  a  black 
ground.  Probably  the  combination  of  black  and  white  is  interpreted 


CH.  LVIII.]  RETINAL  CHANGES   DURING   ACTIVITY  847 

as  indicating  a  polished  surface,  because  a  polished  surface  reflects 
rays  irregularly,  so  that  the  two  eyes  receive  stimuli  of  unequal 
intensity. 

Changes  in  the  Retina  during  Activity. 

The  method  by  which  a  ray  of  light  is  able  to  stimulate  the 
endings  of  the  optic  nerve  in  the  retina  in  such  a  manner  that  a 
visual  sensation  is  perceived  by  the  cerebrum,  is  not  yet  understood. 
It  is  supposed  that  the  change  effected  by  the  agency  of  the  light 
which  falls  upon  the  retina  is  in  fact  a  physico-chemical  alteration  in 
the  protoplasm,  and  that  this  change  stimulates  the  optic  nerve-end- 
ings. The  discovery  of  a  certain  temporary  reddish-purple  pigmenta- 
tion of  the  outer  limbs  of  the  retinal  rods  in  certain  animals  (e.g. 
frogs)  which  had  been  killed  in  the  dark,  forming  the  so-called  rhodopsin 
or  visual  purple,  appeared  likely  to  offer  some  explanation  of  the 
matter,  especially  as  it  was  also  found  that  the  pigmentation  dis- 
appeared when  the  retina  was  exposed  to  light,  and  reappeared  when 
the  light  was  removed,  and  also  that  it  underwent  distinct  changes 
of  colour  when  other  than  white  light  was  used.  It  was  also  found 
that  if  the  operation  were  performed  quickly  enough,  the  bleached 
image  of  a  bright  object  (optogram)  might  be  fixed  on  the  retina  by 
soaking  the  retina  of  an  animal  which  has  been  killed  in  the  dark,  in 
alum  solution. 

The  rhodopsin  is  derived  in  some  way  from  the  black  pigment 
(melanin  or  fuscin)  of  the  polygonal  epithelium  of  the  retina,  since 
the  colour  is  not  renewed  after  bleaching,  if  the  retina  is  detached 
from  its  pigment  layer. 

Certain  pigments,  not  sensitive  to  light,  are  contained  in  the  inner 
segments  of  the  cones.  These  are  oil  globules  of  various  colours,  red, 
green,  and  yellow,  called  chromophanes,  and  are  found  in  the  retinae 
of  marsupials  (but  not  other  mammals),  birds,  reptiles,  and  fishes. 
Nothing  is  known  about  the  yellow  pigment  of  the  yellow  spot. 

Another  change  produced  by  the  action  of  the  light  upon  the 
retina  is  the  movement  of  the  pigment  cells.  On  being  stimulated  by 
light  the  granules  of  pigment  in  the  cells  which  overlie  the  outer 
part  of  the  rod  and  cone  layer  of  the  retina  pass  down  into  the 
processes  of  the  cells,  which  hang  down  between  the  rods:  these 
melanin  or  fuscin  granules  are  generally  rod-shaped,  and  look  almost 
like  crystals.  In  addition  to  this,  a  movement  of  the  cones  and  possibly 
of  the  rods  occurs,  as  has  been  already  mentioned ;  in  the  light  the 
cones  shorten,  and  in  the  dark  they  lengthen  (Engelmann). 

Red  light  has  no  action  on  visual  purple ;  the  maximum  bleach- 
ing effect  takes  place  in  greenish-yellow  light.  Now,  when  the  living 
eye  is  brought  into  a  condition  of  "  dark  adaptation,"  that  is,  when 


848  THE   EYE   AND   VISION  [CH.  LV1II. 

the  retina  has  become  adapted  to  light  of  low  intensity,  the  colours 
of  the  spectrum  alter  in  brightness ;  the  red  end  becomes  shortened 
and  much  darker ;  the  blue  end  becomes  brighter,  and  the  region  of 
maximum  brightness  is  in  the  green.  This  change  of  brightness 
with  change  of  adaptation,  known  as  Purkinge's  phenomenon,  is 
absent  in  the  fovea,  where  there  are  no  rods.  The  selective  action 
of  the  colours  of  the  spectrum  on  the  visual  purple  is  so  strikingly 
similar  to  the  altered  conditions  of  brightness  just  described,  that 
changes  in  the  visual  purple  of  the  rods  have  been  supposed  to  be 
the  cause  of  sensations  excited  by  feeble  illumination  (i.e.  in  the 
"dark-adapted"  eye),  while  the  cones  are  affected  under  more 
ordinary  conditions  of  illumination.  This  conclusion  gains  support 
from  several  interesting  facts.  Visual  purple  is  specially  abundant 
in  the  retinae  of  almost  all  animals  whose  habits  are  nocturnal,  or 
who  live  underground.  Further,  if  the  intensity  of  a  colour  stimulus 
is  gradually  increased,  it  at  first  is  too  faint  to  produce  any  sensa- 
tion ;  then  it  produces  a  sensation  of  greyness,  and  at  last  the  colour 
itself  is  seen ;  the  interval  between  the  appearance  of  the  grey  or 
white-black  effect  and  of  the  true  colour  effect  of  the  stimulus  is 
spoken  of  as  the  "photo-chromatic  interval."  Eed  light  has  no  effect 
on  visual  purple,  and  has  no  photo-chromatic  interval  (that  is,  it 
appears  either  red  or  nothing),  and  according  to  several  observers, 
there  is  no  such  interval  at  the  fovea,  where  the  rods,  and  therefore 
visual  purple,  are  absent.  Thirdly,  a  very  similar  effect  has  been 
described  by  M'Dougall,  when  the  retina  is  momentarily  stimulated 
by  a  coloured  light ;  the  sensation  arising  from  the  stimulus  is 
followed  by  a  series  of  "  primary  responses  "  or  after-sensations ;  the 
first  members  of  the  series  have  the  same  colour  as  the  stimulus, 
and  these  are  sometimes  followed  by  a  series  of  colourless  (grey) 
sensations ;  these  grey  sensations  are  only  present  outside  the  fovea, 
and  under  conditions  of  "  dark  adaptation "  are  absent  with  red  and 
brightest  with  green  stimuli.  Here  again  we  are  able  to  differentiate 
between  a  visual-purple  (rod)  effect,  and  a  cone  effect,  the  former, 
active  under  conditions  of  feeble  illumination,  affected  most  by  green 
and  unaffected  by  red  light,  and  yielding  colourless  sensations ;  the 
latter  being  more  specially  concerned  in  developing  sensations  of 
colour  under  conditions  of  adaptation  to  ordinary  light.  The  fovea 
centralis  thus  becomes  the  region  where  the  colours  of  objects  are 
best  distinguishable,  and  where  with  ordinary  illumination  visual 
acuity  is  most  marked.  In  the  dark,  however,  extra-foveal  (rod) 
vision  is  more  sensitive  than  foveal  (cone)  vision ;  astronomers  see 
faint  stars  more  readily  in  the  periphery  of  the  field  of  vision. 

Two  abnormal  conditions  may  be  described  here,  for  they  throw  light  on  these 
phenomena.  In  cases  of  achromatopsia  (total  colour-blindness)  the  spectrum  is  seen 
as  a  band  of  light  differing  only  in  brightness ;  the  region  of  maximum  brightness 


CH.  LVIIL.]  MOVEMENTS   OF   THE   EYEBALLS  849 

is  the  same  as  in  extra-foveal  vision  of  the  normal  eye ;  in  many  of  these  cases  there 
is  a  central  scotonia  (blind  spot),  that  is,  the  rodless  fovea  is  blind  ;  there  is  reduced 
acuity  of  vision  as  in  the  "  dark-adapted  "  eye,  and  photophobia  (fear  of  strong  light); 
nystagmus  (oscillating  movements  of  the  eye)  also  occurs,  due  to  absence  of  an  area  of 
distinct  vision.  We  are  thus  in  typical  cases  of  achromatopsia  dealing  with  cases 
of  cone  blindness.  In  nyctalopia  (night  blindness),  on  the  other  hand,  we  meet  the 
converse  condition.  Here  there  is  an  abnormal  slowness  of  "  dark  adaptation,"  and 
a  pathological  change  known  as  retinitis  pigmentosa  is  present,  suggesting  an  im- 
paired function  of  the  visual  purple.  Pilocarpine  has  been  found  an  effective  drug 
in  such  cases,  and  this  is  also  interesting  because  it  hastens  the  regeneration  of  visual 
purple  in  the  extirpated  eye. 

The  electrical  variations  in  the  retina  under  the  influence  of  light  were 
discovered  by  M'Kendrick  and  Dewar,  and  have  been  recently  reinvestigated  by 
Waller.  The  excised  eyeball  of  a  frog  is  led  off  by  non-polarisable  electrodes  to  a 
galvanometer.  One  electrode  is  placed  on  the  front,  the  other  on  the  back  of  the 
eye.  If  the  eyeball  is  quite  fresh,  a  current  is  observed  passing  through  the 
eyeball  from  back  to  front.  When  light  falls  on  the  eye  this  current  is  increased  ; 
on  shutting  off  the  light  there  is  a  momentary  further  increase,  and  then  the  current 
slowly  returns  back  to  its  previous  condition.  Waller  explains  this  by  supposing 
that  anabolic  changes  in  the  eye  predominate  during  stimulation  by  light.  With 
the  onset  of  darkness,  the  katabolic  changes  cease  at  once,  and  the  anabolic  more 
slowly ;  hence  a  further  positive  variation. 

As  already  stated,  the  current  in  a  fresh  eyeball  passes  from  back  to  front  before 
the  stimulus  is  applied,  but  this  cannot  be  regarded  as  a  true  current  of  rest,  but  as 
a  current  due  to  previous  action  which  very  slowly  subsides.  When  this  has 
subsided,  the  true  current  of  rest  is  from  cornea  to  fundus,  i.e.,  it  is  like  that 
of  the  skin,  ingoing — the  response  to  stimulation  is  like  that  of  the  skin,  out- 
going. Waller  has  also  studied  the  electrical  responses  of  the  eyeball  to  other 
methods  of  stimulation ;  if 'electrical  currents  are  employed,  and  the  eyeball  is  still 
healthy,  the  response  is  always  an  outgoing  current,  whatever  may  be  the  direction 
of  the  electrical  current  used  as  the  stimulus.  These  currents  of  action  are  no  doubt 
mainly  of  retinal  origin,  but  later  Waller  showed  that  the  anterior  portions  of  the 
eye,  especially  the  crystalline  lens,  participate  in  their  causation.  The  response  of 
the  eye  to  non-luminous  stimuli  lasts  some  time,  and  is  spoken  of  as  a  "  blaze  current" 
An  analogous  response  has  been  seen  in  skin,  plant-tissues,  etc. 

Gotch  has  studied  the  photo-electric  changes  in  the  frog's  eyeball  with  the 
capillary  electrometer.  He,  like  Waller,  draws  attention  to  the  long  latent  period  and 
sustained  character  of  the  response.  The  photo-electric  changes  are  all  monophasic 
effects,  whether  produced  by  illumination,  or  by  shutting  off  the  light  Gotch 
suggests  there  are  two  chemical  substances  in  the  retina,  one  of  which  reacts  to  light, 
the  other  to  darkness.  Each  reaction  is  a  change  of  the  same  type,  but  for  the  change 
to  occur  markedly,  the  eye  must  be  previously  adapted,  i.e.,  the  substances  must 
undergo  a  phase  of  metabolism  under  conditions  opposite  to  those  which  evoke  the 
reaction  effects.  Observations  with  red  and  green  light  do  not  support  the  view 
that  the  photo-chemical  changes  are  of  opposite  characters,  for  the  photo-electric 
change  is  always  in  the  same  direction,  differing  only  in  period  of  latency,  that  for 
red  being  the  longer. 

MOVEMENTS  OF  THE  EYEBALL 

Protrusion  of  the  eyeballs  occurs  (1)  when  the  blood-vessels  of 
the  orbit  are  congested ;  (2)  when  contraction  of  the  plain  muscular 
fibres  of  the  capsule  of  Tenon  takes  place ;  these  are  innervated  by 
the  cervical  sympathetic  nerve;  and  (3)  in  the  disease  called 
exophthalmic  goitre. 

Retraction  occurs  (1)  when  the  lids  are  closed  forcibly;  (2) 
when  the  blood-vessels  of  the  orbit  are  comparatively  empty; 
(3)  when  the  fat  in  the  orbit  is  reduced  in  quantity,  as  during 

3" 


850  THE    EYE   AtfD    VISION  [CH.  LV1II. 

starvation;  and  (4)  on  section  or  paralysis  of  the  cervical  sympa- 
thetic nerves. 

The  most  important  movements,  however,  are  those  produced  by 
the  six  ocular  muscles. 

The  internal  rectus  turns  the  eyeball  inwards,  the  external  rectus 
turns  it  outwards.  If  the  superior  rectus  acted  alone,  it  would  turn 
the  eyeball  not  only  upwards,  but  owing  to  the  sloping  direction  of 
the  muscle,  the  eyeball  would  be  turned  inwards  also ;  in  turning 
the  eyeball  directly  upwards,  this  inward  movement  is  arrested  by 
the  outward  tendency  of  the  inferior  oblique.  Similarly,  in  turning 
the  eyeball  directly  downwards,  the  inferior  rectus  acts  in  conjunc- 
tion with  the  superior  oblique.  Movements  in  intermediate  directions 
are  produced  by  other  combinations  of  the  muscles. 

These  muscles  are  all  supplied  by  the  third  nerve  except  the 
superior  oblique,  which  is  supplied  by  the  fourth,  and  the  external 
rectus  by  the  sixth  nerve. 

The  muscles  of  the  two  eyes  act  simultaneously,  so  that  images 
of  the  objects  looked  at  may  fall  on  corresponding  points  of  the 
two  retinae.  The  inner  side  of  one  retina  corresponds  to  the 
outer  side  of  the  other,  so  that  any  movement  of  one  eye  inwards 
must  be  accompanied  by  a  movement  of  the  other  eye  outwards. 
If  one  eyeball  is  forcibly  fixed  by  pressing  the  finger  against  it  so 
that  it  cannot  follow  the  movement  of  the  other,  the  result  is 
double  vision  (diplopia),  because  the  image  of  the  objects  looked  at 
will  fall  on  points  of  the  two  retinae  which  do  not  correspond.  The 
same  is  experienced  in  a  squint,  until  the  subject  learns  to  disregard 
the  image  from  one  eye. 

If  the  external  rectus  is  paralysed,  the  eye  will  squint  inwards ; 
if  this  occurs  in  the  right  eye  the  false  image  will  lie  on  the  left  side 
of  the  yellow  spot,  and  appear  in  the  field  of  vision  to  the  right  of 
the  true  image.  If  the  third  nerve  is  paralysed,  the  case  is  a  more 
complicated  one:  owing  to  the  paralysis  of  the  levator  palpebrse 
superioris,  the  patient  will  be  unable  to  raise  his  upper  lid  (ptosis), 
and  so  in  order  to  see  will  walk  with  his  chin  in  the  air.  If  the 
paralysis  is  on  the  right  side,  the  eyeball  will  squint  downwards  and 
to  the  right ;  the  false  image  will  be  formed  below  and  to  the  right 
of  the  yellow  spot,  and  the  apparent  image  in  the  field  of  vision  will 
consequently  appear  above  and  to  the  left  of  the  true  image,  and 
owing  to  the  squint  being  an  oblique  one,  the  false  image  will  slant 
in  a  corresponding  direction. 

Various  Positions  of  the  Eyeballs. 

All  the  movements  of  the  eyeball  take  place  around  the  point  of 
rotation,  which  is  situated  177  mm.  behind  the  centre  of  the  visual 
axis,  or  10'9  mm.  behind  the  front  of  the  cornea. 


CH.  LVIII.]  POSITIONS    OF   THE   EYEBALLS  851 

The  three  axes  around  which  the  movements  occur  are : — 

1.  The  visual  or  antero-posterior  axis.     (A  P,  fig.  537.) 

2.  The  transverse  axis,  which  connects  the  points  of  rotation  of 
the  two  eyes.     (Tr,  fig.  537.) 

3.  The  vertical  axis,  which  passes  at  right  angles  to  the  other 
two  axes  through  their  point  of  intersection. 

The  line  which  connects  the  fixed  point  in  the  outer  world  at 
which  the  eye  is  looking  to  the  point  of  rotation  is  called  the  visual 


FIG.  537. — Diagram  of  the  axes  of  rotation  to  the  eye.     The  thin  lines  indicate  axes  of  rotation,  the 
thick  the  position  of  muscular  attachment. 

line.  The  plane  which  passes  through  the  two  visual  lines  is  called 
the  visual  plane. 

The  various  positions  of  the  eyeballs  are  designated  primary, 
secondary,  and  tertiary. 

The  primary  position  occurs  when  both  eyes  are  parallel,  the 
visual  lines  being  horizontal  (as  in  looking  at  the  horizon). 

Secondary  positions  are  of  two  kinds : — 

(1)  The  visual  lines  are  parallel,  but  directed  either  upwards  or 
downwards  from  the  horizontal  (as  in  looking  at  the  sky). 

(2)  The  visual  lines   are   horizontal,  but  converge   towards  one 
another  (as  in  looking  at  a  small  object  near  to  and  on  the  same 
level  as  the  eyes). 

Tertiary  positions  are  those  in  which  the  visual  lines  are  not 
horizontal,  and  converge  towards  one  another  (as  in  looking  at  the 
tip  of  the  nose). 


852 


THE    EYE   AND    VISION 


[CH.  LVIII. 


It  is  possible  to  conceive  positions  of  the  eyeballs  in  which  the 
visual  lines  diverge  from  one  another;  but  such  positions  do  not 
occur  in  normal  vision  in  man. 

Both  eyes  are  moved  simultaneously,  even  if  one  of  them 
happens  to  be  blind.  They  are  moved  so  that  the  object  in  the 
outer  world  is  focussed  on  the  two  yellow  spots,  or  other  corre- 
sponding points  of  the  two  retinae.  The  images  which  do  not  fall 
on  corresponding  points  are  seen  double,  but  these  are  to  a  great 
extent  disregarded  by  the  brain,  which  pays  particular  attention  to 
those  images  which  fall  on  corresponding  points. 

The  accompanying  diagrams  will  assist  us  in  understanding  what 
is  meant  by  corresponding  or  identical  points  of  the  two  retinae. 

If  E  and  L  (fig.  538)  represent  the  right  and  left  retinse 
respectively,  0  and  0'  the  two  yellow  spots  are  identical ;  so  are  A 


FIG.  538. — Identical  points  of  the  retinse. 

and  A',  both  being  the  same  distance  above  0  and  0'.  But  the 
corresponding  point  to  B  on  the  inner  side  of  0  in  the  right  retina, 
is  B',  a  point  to  the  same  distance  on  the  outer  side  of  0'  in  the  left 
retina ;  similarly  C  and  C'  are  identical.  The  two  blind  spots  X  and 
X7  are  not  identical. 

Fig.  539  shows  the  same  thing  in  rather  a  different  way ;  A  and 
B  represent  horizontal  sections  through  the  two  retinas ;  the  points 

a  a',  b  b',  and  c  c',  being  identical. 
In  the  lower  part  of  the  diagram  is 
shown  the  way  in  which  the  brain 
combines  the  images  in  the  two  retinae, 
one  overlapping  so  as  to  coincide  with 
the  other. 

The  Horopter  is  the  name  given  to 
the  surface  in  the  outer  world  which 
contains  all  the  points  which  fall  on 
the  identical  points  of  the  retinse. 

The  shape  of  the  horopter  will  vary  with  the  position  of  the  eye- 
primary  position,  and   in  the   first   variety  of   the 


Fio.  539. — Diagram  to  show  the  correspond- 
ing parts  of  both  retinae. 


balls.  .  In   the 


CH.  LVIIL] 


THE  OPTIC   NERVES 


853 


0— A  -0' 

FIG.  540.— The  Horopter,  when  the 
eyes  are  convergent. 


secondary  position,  the  visual  lines  are  parallel ;  hence  the  horopter 
will  be  a  plane  at  an  infinite  distance. 

In  the  other  variety  of  the  secondary  position,  and  in  tertiary 
positions  in  which  the  visual  lines  converge,  as  when  looking  at  a 
near  object,  the  horopter  is  a  circle  (fig.  540)  which  passes  through  the 
nodal  points  of  the  two  eyes,  and  through 
the  fixed  point  (I)  in  the  outer  world  at 
which  the  eyes  are  looking,  and  which 
will  consequently  fall  on  the  two  yellow 
spots  (0  and  0').  All  other  points  in 
this  circle  (II,  III)  will  fall  on  identical 
points  of  the  retinae.  The  image  of  II 
will  fall  on  A  and  A' ;  of  III  on  B  and  B' ; 
it  is  a  simple  mathematical  problem  to 
prove  that  OA  =  0'A',  and  OB  =  0'B'. 

In  those  animals  in  which  the  eyes 
are  lateral  in  position,  and  the  visual 
lines  diverge,  the  problem  of  binocular 
vision  is  a  very  different  one  (see  also 
p.  736). 

Nervous  Paths  in  the  Optic  Nerves. 

The  correspondence  of  the  two  retinae  and  of  the  movements  of 
the  eyeballs  is  produced  by  a  close  connection  of  the  nervous  centres 
controlling  these  phenomena,  and  by  the  arrangement  of  the  nerve- 
fibres  in  the  optic  nerves.  The  crossing  of  the  nerve-fibres  at  the 
optic  chiasma  is  incomplete,  and  the  next 
diagram  (fig.  541)  gives  a  simple  idea  of  the 
way  the  fibres  go. 

It  will  be  seen  that  it  is  only  the  fibres 
from  the  inner  portions  of  the  retinae  that 
cross;  and  that  those  represented  by  con- 
tinuous lines  from  the  right  side  of  the  two 
retinae  ultimately  reach  the  right  hemisphere, 
and  those  represented  by  interrupted  lines 
from  the  left  side  of  the  two  retinae  ultimately 
reach  the  left  hemisphere.  The  two  halves 
of  the  retinae  are  not,  however,  separated  by 
a  hard-and-fast  line  from  one  another;  this 
is  represented  by  the  two  halves  being  de- 
picted as  slightly  overlapping,  and  this  comes 
to  the  same  thing  as  saying  that  the  central  region  of  each  retina  is 
represented  in  each  hemisphere. 

The  part  of  the  hemisphere  concerned  in  vision  is  the  occipital 
lobe,  and  the  reader  should  turn  back  to  our  previous  consideration 


Left   Retina  Right  Retina 


Hemisphere 


Right 
Hemisphere 


FIG.  541.—  Course  of  fibres  at 
optic  chiasma. 


854 


THE   EYE   AND   VISION 


[CH.  LVIII. 


of  this  subject  in  connection  with  cerebral  localisation,  the  pheno- 
mena of  hemianopsia  and  the  conjugate  deviation  of  head  and 
eyes  (pp.  736,  737). 

Fig.  542,  though  diagrammatic,  will  assist  the  reader  in  more 
fully  comprehending  the  paths  of  visual  impulses,  and  the  central 
connections  of  the  nerves  and  nerve-centres  concerned  in  the  process. 
The  fibres  from  the  retina  to  the  external  geniculate  body  end 
there  by  arborising  around  its  cells,  and  a  fresh  relay  of  fibres  from 


FIG.  542  —Relations  of  nerve  cells  and  fibres  of  visual  apparatus.    (Schafet) 

these  cells  passes  in  the  posterior  part  of  the  internal  capsule  to  the 
cortex  of  the  occipital  lobe.  Those  to  the  anterior  corpus  quadrige- 
minum  are  continued  on  by  a  fresh  relay  to  the  nuclei  of  the  nerves 
concerned  in  eye-movements  (represented  by  the  oculo-motor  nucleus 
in  the  diagram) ;  the  axons  of  the  cortical  cells  pass  to  the  tegmentum, 
whence  a  fresh  relay  continues  the  impulse  to  the  oculo-motor  nucleus. 

Sherrington's  observations  on  binocular  flicker  have  shown  that  there  are 
difficulties  in  accepting  fig.  542  as  a  complete  anatomical  basis  for  the  psychological 
processes  involved  in  binocular  vision,  although  it  is  probably  correct  so  far  as  the 
motor  mechanisms  involved  are  concerned. 

Visual  Judgments. 

The  psychical  or  mental  processes  which  constitute  the  visual 
sensation  proper  have  been  studied  to  a  far  greater  degree  than  is 
possible  in  connection  with  other  forms  of  sensation. 


en.  LVIIL]  VISUAL  JUDGMENTS  855 

We  have  already  seen  that  in  spite  of  the  reversion  of  the  image 
in  the  retina,  the  mind  sees  objects  in  their  proper  position;  this 
is  explained  on  p.  823. 

We  are  also  not  conscious  of  the  blind  spot.  This  is  partly  due 
to  the  fact  that  those  images  which  fall  on  the  blind  spot  of  one  eye 
are  not  focussed  there  in  the  other  eye.  But  even  when  one  looks 
at  objects  with  one  eye,  there  is  no  blank,  for  the  reason  explained 
on  p.  835. 

Our  estimate  of  the  size  of  various  objects  is  based  partly  on  the 
visual  angle  (p.  822)  under  which  they  are  seen,  but  much  more  on  the 
estimate  we  form  of  their  distance.  Thus  a  lofty  mountain  many 
miles  off  may  be  seen  under  the  same  visual  angle  as  a  small  hill 
near  at  hand,  but  we  infer  that  the  former  is  much  the  larger 
object  because  we  know  it  is  much  farther  off  than  the  hill.  Our 
estimate  of  distance  is,  however,  often  erroneous,  and  consequently 
the  estimate  of  size  also.  Thus  persons  seen  walking  on  the  top  of 
a  small  hill  against  a  clear  twilight  sky  appear  unusually  large, 
because  we  over-estimate  their  distance,  and  for  similar  reasons 
most  objects  in  a  fog  appear  immensely  magnified. 

The  action  of  the  sense  of  vision  in  relation  to  external  objects 
is,  therefore,  quite  different  from  that  of  the  sense  of  touch.  The 
objects  of  the  latter  sense  are  immediately  present  to  it ;  and 
our  own  body,  with  which  they  come  in  contact,  is  the  measure  of 
their  size.  The  part  of  a  table  touched  by  the  hand  appears  as  large 
as  the  part  of  the  hand  receiving  an  impression  from  it,  for  the  part 
of  our  body  in  which  a  sensation  is  excited,  is  here  the  measure  by 
which  we  judge  of  the  magnitude  of  the  object.  In  the  sense  of 
vision,  on  the  contrary,  the  images  of  objects  are  mere  fractions  of 
the  objects  themselves,  realised  upon  the  retina,  the  extent  of  which 
remains  constantly  the  same.  But  the  mind,  into  which  the 
sensations  of  vision  are  incorporated,  invests  the  images  of  objects, 
together  with  the  whole  field  of  vision  in  the  retina,  with  very  vary- 
ing dimensions ;  the  relative  size  of  the  image  in  proportion  to  the 
whole  field  of  vision,  or  of  the  affected  parts  of  the  retina  to  the 
whole  retina,  alone  remains  unaltered. 

The  estimation  of  the  form  of  bodies  by  sight  is  the  result  partly 
of  the  mere  sensation,  and  partly  of  the  association  of  ideas.  Since 
the  form  of  the  images  perceived  by  the  retina  depends  wholly  on 
the  outline  of  the  part  of  the  retina  affected,  the  sensation  alone  is 
adequate  to  the  distinction  of  superficial  forms  from  each  other,  as  of 
a  square  from  a  circle.  But  the  idea  of  a  solid  body  such  as  a  sphere, 
or  a  cube,  can  only  be  attained  by  the  action  of  the  mind  construct- 
ing it  from  the  different  superficial  images  seen  in  different  positions 
of  the  eye  with  regard  to  the  object,  and,  as  shown  by  Wheatstone 
and  illustrated  in  the  stereoscope,  from  two  different  perspective  pro- 


856 


THE   EYE   AND   VISION 


[CH.  LVIII. 


jections  of  the  object  being  presented  simultaneously  to  the  mind  by 
the  two  eyes. 

Thus,  if  a  cube  is  held  at  a  moderate  distance  before  the  eyes, 
and  viewed  with  each  eye  successively  while  the  head  is  kept 
perfectly  steady,  A  (fig.  543)  will  be  the  picture  presented  to  the 
right  eye,  and  B  that  seen  by  the  left  eye.  Wheatstone  has  shown 
that  on  this  circumstance  depends  in  a  great  measure  our  conviction 
of  the  solidity  of  an  object,  or  of  its  projection  in  relief.  If  different 
perspective  drawings  of  a  solid  body,  one  representing  the  image 
seen  by  the  right  eye,  the  other  that  seen  by  the  left  (for  example, 
the  drawing  of  a  cube,  A,  B,  fig.  543),  be  presented  to  corresponding 
parts  of  the  two  retinae,  as  may  be  readily  done  by  means  of  the 
stereoscope,  the  mind  will  perceive  not  merely  a  single  representa- 


\ 


FIG.  543.— Diagrams  to  illustrate  how  a  judgment  of  a  figure  of  three  dimensions  is  obtained. 

tion  of  the  object,  but  a  body  projecting  in  relief,  the  exact  counter- 
part of  that  from  which  the  drawings  were  made. 

By  transposing  two  stereoscopic  pictures  a  reverse  effect  is  pro- 
duced; the  elevated  parts  appear  to  be  depressed,  and  vice  versd. 
An  instrument  contrived  with  this  purpose  is  termed  a  pseudoscope. 
Viewed  with  this  instrument  a  bust  appears  as  a  hollow  mask,  and 
as  may  readily  be  imagined  the  effect  is  most  bewildering. 

The  clearness  with  which  the  details  of  an  object  are  perceived 
irrespective  of  accommodation,  would  appear  to  depend  largely  on 
the  number  of  rods  and  cones  which  its  retinal  image  covers.  Hence 
the  nearer  an  object  is  to  the  eye  (within  moderate  limits)  the  more 
clearly  are  all  its  details  seen.  Further,  if  we  want  carefully  to 
examine  any  object,  we  always  direct  the  eyes  straight  to  it,  so  that 
its  image  shall  fall  on  the  two  yellow  spots,  where  an  image  of  a 
given  area  will  cover  a  larger  number  of  cones  than  anywhere  else 
in  the  retina.  ^  Moreover,  as  previously  pointed  out,  each  cone  in  the 
macula  lutea  is  connected  to  a  separate  chain  of  neurons. 

The  importance  of  binocular  vision  is  very  great.  If  an  object  is 
looked  at  with  one  eye  only,  it  is  impossible  to  estimate  its  distance 
by  the  sense  of  vision  alone.  For  instance,  if  one  eye  is  closed 
and  the  other  looks  at  a  wire  or  bar,  it  is  impossible  to  tell 


CH.  LV1II.] 


VISUAL  JUDGMENTS 


857 


whether,  if  some  one  drops  a  small  object,  it  falls  in  front  of  or 
behind  the  bar. 

Visual  judgments  are  not  always  correct;  there  are  a  large 
number  of  puzzles  and  toys  which  depend  on  visual  illusions.  One 
or  two  of  the  best  known  are  represented  in  the  accompanying 
diagrams. 

In  fig.  544,  A,  B,  and  c  are  of  the  same  size ;  but  A  looks  taller 
than  B,  while  c  appears  to  cover  a  less  area  than  either.  The  sub- 

A  B 


D 


FIG.  544.— Diagrams  to  illustrate  visual  illusions. 


division  of  a  space  or  line  increases  its  apparent  size  or  length. 
In  fig.  544  D,  ab  is  equal  to  be.  Vertical  distances  also  are  usually 
over-estimated.  In  fig.  545  the  long  lines  are  parallel,  though 


Fia.  545.— Zollner's  lines 


they  do  not  appear  so,  owing  to  the  influence  of  the  intercrossing 
lines. 


CHAPTEE  LIX 

REPRODUCTION,  DEVELOPMENT,  GROWTH  AND  DEATH 

THE  history  of  the  fully  formed  animal  from  the  ovum,  and  a 
description  of  the  origin  and  formation  of  its  tissues  and  organs, 
constitutes  the  portion  of  biological  science  known  as  embryology. 

The  scientific  discussion  of  embryology  must  not  be  limited  to 
man,  however  important  he  may  be,  but  must  embrace  a  wide  survey 
of  the  whole  animal  kingdom,  because  the  changes  which  occur  in 
the  embryological  history  of  the  highest  animals  forms  a  compressed, 
though  in  many  cases  a  modified  picture  of  the  changes  which  have 
taken  place  in  their  historical  development  from  lower  types,  during 
the  long  and  misty  ages  of  the  past. 

To  attempt  an  adequate  discussion  of  this  large  subject  would 
mean  the  writing  of  a  book  as  long  as  the  present  volume.  It  would 
lead  us  far  into  biological  fields,  and  also  into  discussions  of  a 
philosophical  and  hypothetical  nature  which  would  be  quite  out  of 
place  in  a  physiological  text  book.  All  we  can  do  is  to  put  down 
the  important  facts,  and  specially  to  dwell  on  those  which  have  a 
physiological  bearing.  Evolution  has  in  the  past  been  specially 
studied  from  the  anatomical  point  of  view;  but  it  has  its  physio- 
logical counterpart ;  for  as  structures  increase  in  complexity,  so  also 
does  function  become  correspondingly  differentiated  and  varied. 

The  great  problem  of  evolution  is  associated  with  the  immortal 
name  of  Darwin.  He  showed  that  although  the  offspring  resembles 
the  parents  there  are  always  certain  slight  variations  which  may  be 
transmitted  to  future  generations,  and  in  their  turn  these  are 
magnified  or  admixed  with  other  variations  in  each  succeeding 
generation.  In  the  struggle  for  existence  those  will  survive  in 
which  the  variations  are  beneficial  and  helpful,  so  that  in  the  end  the 
fittest  will  live  on.  The  piling  up  of  variations  which  in  themselves 
may  be  trivial  thus  leads  to  the  development  of  new  types  and 
species,  and  this,  prolonged  over  immense  periods  of  time,  has  led  to 
the  evolution  of  complex  from  simple  forms  of  life. 

The  explanation  of  heredity  is  a  subject  on  which  much  difference 

868 


CH.  LIX.]  HEREDITY  859 

of  opinion  prevails.  It  does,  however,  appear  to  be  pretty  well 
accepted  that  the  material  of  the  nucleus  of  the  male  and  female 
reproductive  elements  is  of  special  importance  in  the  transmission 
of  hereditary  characters.  That  the  chromosomes  of  the  nucleus  are 
of  vital  importance  is  clearly  shown  by  several  facts.  For  instance, 
they  are  constant  in  number  not  only  in  the  cells  of  the  body  but 
in  all  individuals  of  any  particular  species  of  animal  or  plant, 
though  differing  in  number  in  different  species.  The  equal  halving 
of  each  chromosome,  which  occurs  during  mitosis,  maintains  this 
numerical  constancy,  except  in  a  certain  period  of  the  life  history  of 
each  individual,  and  this  period  occurs  in  the  formation  of  the 
reproductive  cells  (often  called  gametes).  During  one  step  in  the 
karyokinetic  cell-division,  half  of  the  normal  number  of  chromo- 
somes are  thrown  out,  and  the  act  of  fertilisation  consists  in  the 
fusion  of  the  male  and  female  gametes;  each  parental  nucleus 
provides  half  the  normal  number  of  chromosomes,  and  thus  the 
fertilised  egg-cell  starts  with  the  full  complement  once  more.  A 
large  number  of  biologists  regard  the  chromosomes  as  the  actual 
bearers  of  the  characters  which  an  organism  inherits  from  its 
parents,  or,  at  any  rate,  adopt  this  view  as  a  working  hypothesis. 
This  places  the  transmission  of  characters  from  parent  to  offspring 
upon  a  material  foundation.  Weismann's  view  that  characters 
acquired  after  birth  are  not  transmissible  rests  mainly  upon  negative 
evidence,  and  so  cannot  be  considered  as  fully  proved. 

The  development  of  the  two  sexes  took  place  fairly  early  in  the 
history  of  the  animal  world,  but  there  are  many  animals  of  the 
simplest  kind  in  which  no  differentiation  of  sex  occurs.  The 
determination  of  sex,  that  is,  why  a  mother  should  bear  at  one  time 
a  male,  at  another  time  a  female  infant,  is  a  question  of  great 
importance,  and  numerous  theories  have  been  advanced  to  explain 
it.  In  certain  invertebrate  animals  there  is  some  evidence  that  sex 
is  preformed  either  in  the  ovum  or  the  spermatozoon,  or  in  both ; 
that  is  to  say,  there  are  male  and  female  ova,  and  male  and  female 
spermatozoa  which  exhibit  slight  differences  of  structure;  the 
question  of  sex  of  the  offspring  will  then  depend  upon  which 
element  predominates  after  union.  Others  hold  that  potentialities 
of  producing  either  sex  are  present  in  all  ova  and  all  spermatozoa, 
and  that  the  ultimate  sex  is  determined  by  some  relationship  which 
is  at  present  unknown,  but  which  in  all  probability  operates  at  the 
time  of  fertilisation. 

The  original  Darwinian  doctrine,  just  stated  in  outline,  has  since 
been  modified  in  several  directions  as  research  has  progressed.  The 
work  of  Weismann  just  alluded  to  is  important.  But  of  all  the 
theories  which  have  been  grafted  upon  the  original  theory,  that  of 
Mendel  is  perhaps  of  the  greatest  interest ;  it  certainly  appeals  to 


860        REPRODUCTION,  DEVELOPMENT,   GROWTH  AND   DEATH       [CH.  LIX. 

the  scientific  mind,  for  it  is  one  which  is  susceptible  of  proof  and 
demonstration.  It  may  be  best  illustrated  by  a  concrete  example. 
If  two  kinds  of  plant,  such  as  dwarf  and  tall  peas,  are  crossed,  the 
seeds  obtained  all  produce  tall  plants;  but  if  the  plants  of  this 
generation  are  crossed,  the  third  generation  contains  25  per  cent, 
dwarf  and  75  per  cent,  of  tall  plants.  If  the  dwarfs  are  crossed, 
they  breed  true,  that  is,  they  produce  dwarf  plants  only ;  but  if  the 
tali  plants  are  inter-crossed,  again  one-quarter  of  the  next  generation 
are  dwarfs  and  the  remainder  tall.  Of  the  75  tall  plants,  25  breed 
true,  and  of  the  remaining  50,  one-quarter  produce  dwarfs  which 
breed  true,  and  the  remaining  three-quarters  are  tall  plants.  In 
successive  generations  the  same  holds :  the  dwarfs,  when  self-crossed, 
always  produce  dwarfs,  and  tall  plants  always  produce  a  progeny  in 
which  25  per  cent,  are  dwarfs  and  75  per  cent,  tall,  some  of  which 
breed  true  and  the  remainder  breed  a  mixture  in  the  same  pro- 
portions as  before. 

This  is  explained  by  calling  certain  characters  dominant 
and  others  recessive;  thus,  in  the  example  taken,  tallness  is 
dominant  and  dwarfness  is  recessive.  So  in  the  first  generation  the 
progeny  all  exhibit  the  dominant  character,  but  in  the  second  only 
25  per  cent,  will  be  pure  dominants  (that  is,  will  produce  only 
dominants  in  successive  generations),  25  per  cent,  will  be  pure 
recessives,  and  50  per  cent,  are  mixed;  and  the  mixed  type  will 
again  produce  25  per  cent,  dominants,  25  per  cent,  recessives,  and 
50  per  cent,  mixed,  as  before. 

This  discovery  has  been  found  important  for  breeders  and 
horticulturists,  but  the  law  appears  to  fail  sometimes;  for  instance, 
when  the  black  and  white  races  intermarry,  the  result  is  brown 
children,  and  not  a  definite  proportion  of  blacks  and  whites. 

Looked  at  from  the  evolutionary  point  of  view,  the  whole  of  the 
complex  animal  body  is  but  the  temporary  dwelling-place  of  the 
reproductive  cells,  and  nature  provides  lavishly,  both  in  animals  and 
plants,  for  the  continuance  of  the  species.  These  temporary  homes, 
which  we  call  the  father  and  the  mother,  pass  away,  but  they  live  on 
and  on  in  their  descendants.  In  the  future  we  cannot  doubt  that 
upward  progress  will  still  continue  as  in  the  past,  and  man  in  time 
should  be  in  very  truth  "  but  little  lower  than  the  angels."  Some 
hold  that  civilisation  in  some  ways  places  a  slight  obstacle  on  the 
path  of  progress  of  the  race;  numerous  works  of  charity  militate 
against  the  inexorable  law  of  the  survival  of  the  fittest,  so  that 
many  live  to  propagate  their  species  who  may  be  weaklings  both  in 
body  and  mind.  There  are  no  doubt  extreme  cases  where  it  is 
desirable  that  deteriorated  characters  should  be  debarred  from 
introducing  into  the  world  a  continuance  of  beings  destined  for 
misery  and  crime.  But  I  myself  believe  that  the  present  development 


CH.  LIX.]  THE   CYCLE   OF  LIFE  861 

of  charitable  endeavours  is  in  itself  a  sign  of  progress ;  it  indicates 
a  growth  of  the  feelings  of  compassion  and  unselfishness  which  con- 
stitute a  great  asset  in  the  possessions  of  a  race.  The  laws  of  evolu- 
tion operate  in  spite  of  artificial  hindrances ;  this  is  exemplified  in 
what  is  termed  the  law  of  anticipation ;  by  this  is  meant  that  in  a 
heritable  disease  its  effects  develop  at  an  earlier  and  earlier  age  in 
successive  generations,  until  at  last  it  causes  death  at  a  period 
before  the  sexual  organs  attain  maturity,  and  thus  automatically  its 
continued  propagation  is  put  a  stop  to. 

In  a  simple  unicellular  organism  such  as  the  amoeba,  there  is  not 
only  no  differentiation  of  sex,  but  there  is  also  no  differentiation 
between  the  reproductive  element  (Weismann's  germ  plasm)  and 
the  remainder  of  the  body  (Weismann's  somatoplasm).  When  the 
amoeba  propagates  itself  by  dividing  into  two  new  amoebae,  the 
whole  animal  is  concerned  in  the  act  of  reproduction,  and,  barring 
accidents,  the  new  amoebae  may  behave  in  this  way  indefinitely,  and 
so  may  be  spoken  of  as  immortal.  In  this  sense  the  only  part  of 
the  body  which  is  immortal  (in  the  material  as  opposed  to  the  theo- 
logical use  of  the  word)  in  the  higher  animals  is  the  germ  plasm, 
which  lives  beyond  us  to  repeat  the  process  an  infinite  number  of 
times  in  our  descendants. 

If  now  we  deal  in  a  more  matter-of-fact  way  with  the  present 
instead  of  the  past  or  the  future,  the  faculty  which  living  organisms 
have  of  reproducing  themselves  furnishes  us  with  a  new  conception 
of  the  life  process.  The  common  lot  of  all  is  to  die,  and  life  in  the 
individual  is  then  extinct ;  but  each  individual  is  only  a  link  in  a 
long  chain  of  lives,  and  life  is  thus  not  something  which  begins  and 
ends  like  &  straight  line ;  it  is  rather  to  be  compared  to  a  circle,  in 
which  a  series  of  events  is  repeated  over  and  over  again.  If  we 
start  with  the  ovum  we  are  led  to  the  foetus,  and  then  to  the  child, 
and  the  adult  who  produces  or  fertilises  an  ovum  once  more ;  and 
so  history  goes  on  repeating  itself. 

I  propose,  however,  in  the  following  account  of  some  of  the 
details  of  the  long  story,  to  start  at  a  different  point  in  the  cycle. 
We  will  take  first  the  new-born  child,  and  rapidly  run  through  what 
occurs  after  its  birth  until  the  state  of  sexual  maturity  is  reached. 
Next  it  will  be  our  duty  to  consider  the  structure  and  physiology 
of  the  reproductive  organs,  and  how  the  ova  in  one  sex,  and  the 
spermatozoa  in  the  other  sex,  originate.  Next  will  follow  an  account 
of  the  union  of  these  reproductive  cells,  and  the  production  of  a 
fertilised  ovum.  This  will  be  followed  by  a  brief  account  of  the 
development  and  life  of  the  foetus,  until  we  reach  the  mechanism  by 
which  the  new-born  child  is  expelled  from  the  uterus  into  the  world, 
which  will  bring  us  back  to  the  point  from  which  we  started. 


862      REPRODUCTION,  DEVELOPMENT,  GROWTH  AND  DEATH     [CH.  L1X. 

THE  NEW-BORN  CHILD  AND  THE  CHANGES  IT  UNDERGOES 
AFTER  BIRTH. 

The  new-born  child,  which  in  the  uterus  was  obtaining  its 
nutriment  and  oxygen  from  its  mother's  blood,  is  severed  from  the 
organ  called  the  placenta,  by  means  of  which  this  was  accomplished, 
by  cutting  through  the  umbilical  cord.  The  want  of  oxygen  is  met 
by  the  child  beginning  to  breathe,  and  its  nutriment  is  supplied  by 
its  mother's  milk,  which  later  on  is  supplemented  and  replaced  by 
other  articles  of  diet.  Immediately  after  birth  certain  changes 
occur  in  the  circulatory  system;  the  foramen  ovale,  the  opening 
between  the  two  auricles,  begins  to  close,  and  so  do  the  ductus 
arteriosus  and  the  ductus  venosus.  The  now  functionless  umbilical 
vessels  close  also  until  they  are  reduced  to  mere  fibrous  cords. 
These  changes  are  completed  in  a  few  days,  and  the  circulation  then 
takes  the  course  it  traverses  for  the  rest  of  life. 

In  addition  to  this  there  are  changes  of  a  more  general  kind,  the 
most  obvious  of  which  is  growth;  this  is  accompanied  with  the 
completion  in  the  formation  of  certain  organs  and  tissues  which  are 
in  a  comparatively  immature  condition  when  the  child  is  born. 
Thus  medulla tion  of  the  fibres  in  the  central  nervous  system  is 
taking  place,  and  the  process  of  ossification  continues  until  the 
bony  skeleton  is  perfected.  The  generative  organs  reach  maturity 
at  the  period  of  life  known  as  puberty. 

The  rate  of  growth  after  birth  is  not  so  rapid  as  it  is  in  utero ; 
and  every  year  the  relative  increase  in  size  gets  less  and  less.  On 
the  average,  girls  in  the  earlier  years  grow  more  than  boys,  but  at  the 
onset  of  puberty  this  relationship  is  usually  reversed.  At  puberty 
there  is  generally  an  acceleration  of  the  rate  of  growth  in  both  sexes, 
but  this  gradually  declines,  and  finally  growth  ceases. 

Puberty  then  is  the  period  at  which  the  sexual  organs  become 
matured  and  functional.  In  girls  this  occurs  on  the  average  at 
about  fourteen  or  fifteen  years  of  age,  and  is  marked  by  the  onset  of 
menstruation.  Menstruation,  or  the  monthly  flow,  continues  until 
the  age  of  forty-five  to  fifty,  when  it  ceases  either  gradually  or 
suddenly,  and  after  this  period  (the  menopause  or  climacteric)  further 
production  of  offspring  is  not  possible.  The  menopause  is  usually 
accompanied  with  great  depression  and  other  disturbances  of  a 
physical  and  mental  nature. 

In  boys,  puberty  is  usually  a  little  later  developed  than  in  girls, 
but  there  is  no  limit  at  the  other  end  of  life  corresponding  to  the 
menopause. 

In  both  sexes  the  onset  of  puberty  is  accompanied  by  the 
secondary  sexual  characters  becoming  pronounced,  such  as  the 
increase  in  fullness  of  the  mammary  glands  in  the  female,  and  the 


CH.  LIX.] 


THE   MALE   REPRODUCTIVE   ORGANS 


863 


growth  of  hair  on  the  face  and  the  increase  in  size  of  the  larynx  which 
leads  to  the  deepening  of  the  pitch  of  the  voice  in  the  male. 

THE  MALE  REPRODUCTIVE  ORGANS 

These  consist  of  the  two  testes  which  produce  spermatozoa,  and 
the  ducts  which  lead  from  them. 

The  testis  is  enclosed  in  a  serous  membrane  called  the  tunica 
vaginalis,  originally  a  part  of  the  peritoneum,  which  descends  into  the 


FIG.  546. — Plan  of  a  vertical 
section  of  the  testicle, 
showing  the  arrangement 
of  the  ducts.  The  true 
length  and  diameter  of  the 
ducts  have  been  disre- 
garded, a  a,  Tubuli  semi- 
niferi  coiled  up  in  the 
separate  lobes ;  &,  tubuli 
recti ;  c,  rete  testis  ;  d,  vasa 
efferentia  ending  in  the  coni 
vasculosi ;  I,  e,  g,  convo- 
luted canal  of  the  epidi- 
dymis;  h,  vas  deferens; 
/,  body  of  Highmore  ;  i  i, 
librous  processes  running 
between  the  lobes. 


FIG.  547.— Section  of  the  epididymis  of 
a  dog.— The  tube  is  cut  in  several 
places,  both  transversely  and  ob- 
liquely ;  it  is  seen  to  be  lined  by  a 
ciliated  epithelium,  the  nuclei  of 
which  are  well  shown,  c,  Connec- 
tive tissue.  (Schofield.) 


scrotum  before  the  testis  and  subsequently  gets  entirely  cut  off 
from  the  remainder  of  the  peritoneum.  There  are,  however,  many 
animals  in  which  the  testes  remain  permanently  in  the  abdomen. 
The  external  covering  of  the  testicle  itself  is  a  strong  fibrous  capsule, 
called,  on  account  of  its  white  appearance,  the  tunica  albuginea. 
Passing  from  its  inner  surface  are  a  number  of  septa  or  trabeculae, 
which  divide  the  organ  imperfectly  into  lobules.  On  the  posterior 
aspect  of  the  organ  the  capsule  is  greatly  thickened,  and  forms  a  mass 
of  fibrous  tissue  called  the  Corpus  Highmorianum  (body  of  High- 


864        REPRODUCTION,   DEVELOPMENT,   GROWTH  AND   DEATH      [CH.  LIX. 

more)  or  mediastinum  testis.  Attached  to  this  is  a  much  convoluted 
tube,  which  forms  a  mass  called  the  epididymis.  This  receives  the 
ducts  of  the  testis,  and  is  prolonged  into  a  thick -walled  tube,  the  vas 
deferens,  by  which  the  semen  passes  to  the  urethra. 

Each  lobule  of  the  testicle  contains  several  convoluted  tubes. 
Every  tube  commences  near  the  tunica  albuginea,  and  terminates 
after  joining  with  others  in  a  straight  tubule,  which  passes  into  the 
body  of  Highmore,  where  it  ends  in  a  network  of  tubes,  the  rete  testis. 
From  the  rete  about  fifteen  efferent  ducts  (vasa  efferentia)  arise, 
which  become  convoluted  to  form  the  coni  vasculosi,  and  then  pass 
into  the  tube  of  the  epididymis. 

The  convoluted  or  seminiferous  tubes  (fig.  548)  have  the  following 


^v 

7^  ®J>®JI  SS  ^  ® .      ^V4 


FIG.  548.— Diagram  of  a  portion  of  a  seminal  tubule  showing  development  of  spermatozoa.  1,  Primi- 
tive germ  cell ;  2,  spermatogonia ;  3,  primary  spermatocytes ;  4,  secondary  spermatocytes ;  5, 
spermatids,  some  with  commencement  of  axial  lilament ;  C,  a  nurse  cell  with  spermatids  and 
spermatozoa  in  various  stages  of  development ;  7,  free  spermatozoa  in  lumen  of  tube  ;  8,  portions 
of  nurse  cells.  (After  Waldeyer.) 

structure :  each  consists  of  (1)  an  outer  boundary  of  flattened  connec- 
tive-tissue cells  intermingled  with  elastic  fibres ;  (2)  a  fine  membrana 
propria;  (3)  a  lining  epithelium  of  many  layers  of  germinal  cells. 
Next  to  the  membrana  propria  is  a  layer  of  cells,  some  of  which  are 
primordial  germinal  cells,  others  are  spermatogonia  produced  from  the 
primordial  germinal  cells,  but  differing  from  them  in  structure,  and 
the  remainder  are  supporting  or  nurse  cells  (Cells  of  Sertoli)  which 
provide  nutriment  for  the  developing  spermatozoa.  More  internally, 
between  the  projecting  processes  of  the  nurse  cells,  are  large  primary 
spermatocytes,  derived  from  the  division  of  the  spermatogonia.  Still 
nearer  the  lumen  of  the  tube  lie  the  secondary  spermatocytes ,  which 
are  the  daughter-cells  of  the  primary  spermatocytes;  the  secondary 


CH.  LIX.] 


THE  TESTIS 


865 


spermatocytes  give  rise  by  division  to  the  spermatids  which  lie  next 
the  lumen.  The  spermatids  become  imbedded  in  the  inner  ends  of 
the  nurse  cells,  where  they  grow  and  become  converted  into 


FIG.  549.— A  spermatic!  largely 
magnified.  1,  nucleus;  2, 
nucleolus ;  3,  chromatoid 
body ;  4,  idiosome ;  5,  centro- 
somes ;  6,  commencement  of 
axial  filament.  (After  Meves.) 


FIG.  550.— Cells  of  the 
interstitial  tissue  of 
the  testis  with  crystal- 
loid bodies. 


spermatozoa.  Every  spermatid  contains  a  nucleus,  and  near  the 
nucleus  is  another  structure  called  an  idiosome,  containing  a  number 
of  microsomes.  There  are  also  a  coloured  or  chromatoid  body  whose 
function  is  not  known,  and  two  centrosomes  (see  fig.  549). 

The  interstitial  connective  tissue  of  the  testis  is  loose,  and  con- 
tains numerous  lymphatic  clefts.  Lying  in  it,  accompanying  the  blood- 
vessels, are  strands  of  polyhedral 
epithelial  cells,  of  a  yellowish  colour 
(interstitial  cells),  which  frequently 
contain  crystalloid  bodies  (fig.  550). 

The  straight  tubules  consist  of 
basement  membrane  and  lining  cubi- 
cal epithelium  only.  The  tubules  of 
the  rete  testis  are  lined  by  cubical 
epithelium ;  the  basement  membrane 
is  absent.  The  vasa  efferentia,  coni 
vasculosi,  and  epididymis  are  lined 
by  columnar  cells,  some  of  which  are 
ciliated,  whilst  others  are  devoid  of 
cilia,  and  probably  possess  secretory 
functions.  There  is  a  good  deal  of 
muscular  tissue  in  their  walls.  The 
vas  deferens  consists  of  a  muscular 
wall  (outer  layer  longitudinal,  middle 

circular,  inner  longitudinal),  lined  by  a  mucous  membrane,  the 
inner  surface  of  which  is  covered  by  columnar  epithelium. 

The  vesiculce  seminales  are  outgrowths  of  the  vasa  def erentia.    Each 

3  i 


-c 


FIG.  551.— Erectile  tissue  of  the  human  penis, 
a,  Fibrous  trabeculse  with  their  ordinary 
capillaries ;  b,  section  of  the  veoous  sinuses ; 
c,  muscular  tissue.  (Cadiat.) 


866         REPRODUCTION,    DEVELOPMENT,    GROWTH   AND   DEATH       [CH.  L1X. 


is  a  much  convoluted,  branched,  and  sacculated  tube  of  structure 
similar  to  that  of  the  vas  def erens,  except  that  the  wall  is  thinner ; 
their  secretion  is  added  to  the  semen,  as  is  also  the  secretion  of  the 
glands  of  the  prostate. 

The  penis  is  composed  of  cavernous  tissue  covered  by  skin. 
The  cavernous  tissue  is  collected  into  three  tracts,  the  two  corpora 
cavernosa  and  the  corpus  spongiosum  in  the  middle  line  inferiorly. 


— 4 


—  5 


—3 


—4 


— 5 


FIG.  552. — Semi -diagrammatic  representation  of 
human  spermatozoa.  A,  front  view ;  B,  side 
view.  1,  Head  cap  surrounding  head ;  2, 
neck  ;  3,  body  ;  4,  tail ;  5,  end-piece.  The 
axial  filament  runs  through  the  body  and 
tail  into  the  end-piece. 


FIG.  553.— Diagram  of 
part  of  a  human  sper- 
matozoon highly  mag- 
nified (after  Meves). 
1,  Head  cap  ;  2,  head  ; 
3,  anterior  centrosome 
in  neck ;  4,  posterior 
centrosome  in  neck  ;  5, 
axial  filament;  6,  spiral 
sheath ;  7,  sheath  of 
axial  filament  in  body  ; 
8,mitochondrial  sheath; 
9,  annulus ;  10,  thick 
sheath  of  axial  filament 
in  tail. 


All  these  are  enclosed  in  a  capsule  of  fibrous  and  plain  muscular 
tissue;  the  septa  which  are  continued  in  from  this  capsule,  form 
the  boundaries  of  the  cavernous  venous  spaces  of  the  tissue.  The 
arteries  run  in  the  septa;  the  capillaries  open  into  th'e  venous 
spaces.  The  arteries  are  often  called  helicine,  as  in  injected  specimens 
they  form  twisted  loops  projecting  into  the  cavernous  spaces  (see 
also  pp.  313,  314). 


CH.  LIX.] 


THE  FEMALE  REPRODUCTIVE  ORGANS 


867 


The  Spermatozoa,  suspended  in  a  richly  albuminous  fluid,  con- 
stitute the  semen.  Each  spermatozoon  consists  of  a  head,  a  very 
short  neck,  a  body,  a  tail,  and  an  end-piece.  The  head  is  of  flattened 
ovoid  shape,  and  in  the  anterior  two-thirds  of  its  extent  is  surmounted 
by  a  head-cap  which,  sharpened  at  its  extremity,  forms  a  cutting 
edge.  The  neck  is  very  short,  and  contains  two  centrosomes.  The 
body  is  about  the  same  length  as  the  head ;  it  is  traversed  by  an 
axial  filament  and  a  spiral  fibril  wound  round  the  sheath  of  the 
axial  filament.  More  externally  is  a  layer  called  the  mitochondrial 
sheath,  which  terminates  at  the  junction  with  the  tail  on  an  annular 
disc.  The  axial  filament  is  continued  through  the  tail  into  the  end- 
piece,  and  in  the  tail  is  surrounded  by  thick  sheath.  In  some 
animals,  newts  and  salamanders,  the  tail  is  surrounded  by  a  spiral 
membrane,  but  this  is  not  present  in  the  human  spermatozoon. 
The  head  of  the  spermatozoon  is  formed  from  the  nucleus  of  the 
spermatid,  the  head-cap  from  the  idiosome ;  the  centrosomes  of  the 
spermatid  pass  to  the  neck,  and  the  cytoplasm  of  the  spermatid 
is  transformed  into  the  parts  of  the  body  and  tail  of  the 
spermatozoon. 

THE  FEMALE  EEPRODUCTIVE  ORGANS 

These  consist  of  the  two  ovaries  which  produce  ova,  and  the  uterus 
with  the  Fallopian  tubes  and  vagina  which  are  continuous  with  it. 


Fio.  554. — Diagrammatic  view  of  the  uterus  and  its  appendages,  as  seen  from  behind.  The  utenia  and 
upper  part  of  the  vagina  have  be«n  laid  open  by  removing  the  posterior  wall ;  the  Fallopian  tube, 
round  ligament,  and  ovarian  ligament  have  been  cut  short,  and  the  broad  ligament  removed  oil  the 
left  side ;  u,  the  upper  part  of  the  uterus  ;  c,  the  cervix  opposite  the  os  internum  ;  the  triangular 
shape  of  the  uterine  cavity  is  shown,  and  the  dilatation  of  the  cervical  cavity  with  the  rugse  termed 
arbor  vit;e  ;  v,  upper  part  of  the  vagina  ;  od,  Fallopian  tube  or  oviduct ;  the  narrow  communication 
of  its  cavity  with  that  of  the  cornu  of  the  uterus  on  each  side  is  seen  ;  I,  round  ligament ;  lo,  liga- 
ment of  the  ovary ;  o,  ovary ;  i,  wide  outer  part  of  the  right  Fallopian  tube ;  fl,  its  limbriated 
extremity  ;  po,  parovarium  ;  h,  one  of  the  hydatids  frequently  found  connected  with  the  broad  liga- 
ment. £.  (Allen  Thomson.) 

The  Ovary  is  composed  of    fibrous  tissue  (stroma)  containing, 
near   its   attachment   to   the   broad   ligament,  a   number   of  plain 


868    REPRODUCTION,  DEVELOPMENT,  GROWTH  AND  DEATH   [CH.  UX. 

muscular  fibres.     It  is  covered  by  a  layer  of  cubical  cells,  called 
the  germinal  epithelium,  which,  in  young  animals,  is  seen  dipping 


FIG.  555. — View  of  a  section  of  the  ovaiy  of  the  cat.  1,  Outer  covering  and  free  border  of  the  ovary ;  I*, 
attached  border ;  2,  the  ovarian  stroma,  presenting  a  fibrous  and  vascular  structure ;  3,  granular 
substance  lying  external  to  the  fibrous  stroma ;  4,  blood-vessels ;  5,  primary  oocytes  in  their  earliest 
stages  occupying  a  part  of  the  granular  layer  near  the  surface ;  6,  oocytes  which  have  begun  to 
enlarge  and  to  pass  more  deeply  into  the  ovary ;  7,  oocytes  round  which  the  Graafian  follicle  and 
tunica  granulosa  are  now  formed,  and  which  have  passed  somewhat  deeper  into  the  ovary  and  are 
surrounded  by  the  fibrous  stroma ;  8,  more  advanced  Graafian  follicle  with  the  oocyte  imbedded  in 
the  layer  of  cells  constituting  the  proligerous  disc ;  9,  the  most  advanced  follicle  containing  the 
oocyte,  etc.;  9',  a  follicle  from  which  the  oocyte  has  accidentally  escaped;  10,  corpus  luteum. 
(Schron.) 

down,  here  and  there,  into  the  stroma.  The  stroma  contains  a 
number  of  yellow  polyhedral  cells  similar  to  the  interstitial  cells  of 
the  testicle. 


^V^^??-^^5ffifS^2^ 


FIG.  556. — Section  of  the  ovary  of  a  cat.  A,  germinal  epithelium  ;  B,  immature  Graafian  follicle ;  C, 
stroma  of  ovary ;  D,  zona  pellucida  surrounding  the  primary  oocyte;  E,  Graafian  follicle  showing 
lining  cells ;  F,  follicle  from  which  the  oocyte  has  fallen  out.  (V.  D.  Harris.) 

Sections  of  the  ovary  show  that  the  stroma  is  crowded  with  a 
number  of  rounded  cells,  the  oocytes,  derived  from  primitive  germ 


CH.  LIX.] 


THE   GRAAFIAN   FOLLICLES 


869 


cells,  which,  in  the  early  stages,  were  intermingled  with  the  cells  of 
the  germinal  epithelium.  There  are  also  numerous  vesicles  of  differ- 
ent sizes  which  are  called  Grraafian  follicles.  The  smallest  follicles 
are  near  the  surface,  the  largest  are  deeply  placed,  but  as  they  ex- 
pand they  again  approach  the  surface,  and  ultimately  rupture  upon  it. 
A  Grraafian  follicle  has  an  external  wall  formed  by  the  stroma ; 
this  is  lined  internally  by  a  layer  of  cells,  derived  from  the  germinal 
epithelium,  which  surrounds  the  oocyte.  At  a  later  stage  there  are 
two  layers  of  cells,  one  lining  the  cavity,  and  the  other  surrounding 


Fia.  557. — Corpus  luteum  of  mouse,  showing  its  formation  completed.  The  central  cavity  is  occupied 
by  jelly-like  connective  tissue;  the  converging  trabeculae  anastomose  with  one  another  so  as 
somewhat  to  break  up  the  columnar  arrangement  of  the  luteal  cells.  (Sobotta.)  (From  Schafer's 
Text-look  of  Microscopic  Anatomy.) 

the  oocyte,  but  the  two  are  close  together.     A  viscid  fluid  collects 
between  the  two,  and  as  the  follicle  grows,  separates  them. 

The  cells  in  each  layer  multiply,  and  are  eventually  arranged  in 
several  strata.  The  lining  epithelium  of  the  follicle  is  then  called 
the  membrana  granulosa,  and  the  heaped  mass  of  cells  around  the 
oocyte,  the  discus  proligerus.  The  fluid  increases  in  quantity,  the 
follicle  becomes  tenser,  and  finally  it  reaches  the  surface  of  the  organ 
and  bursts ;  the  oocyte  or  ovarian  ovum  is  thus  set  free ;  it  enters 
the  fringed  end  of  the  Fallopian  tube  and  thence  passes  to  the 
uterus.  This  process  is  called  ovulation,  and  in  the  human  female 
the  ripening  of  an  ovum  occurs  about  once  every  four  weeks. 


870    REPRODUCTION,  DEVELOPMENT,  GROWTH  AND  DEATH   [CH.  LIX. 


After  the  rupture  of  the  Graafian  follicle,  it  is  filled  up  with  what 
is  known  as  a  corpus  luteum.  This  is  derived  from  the  wall  of  the 
follicle,  and  consists  of  columns  of  yellow  cells  developed  from  the 
hypertrophy  of  the  epithelial  cells  of  the  membrana  granulosa;  it 
often  contains  at  first  a  blood-clot  in  its  centre.  The  strands  of  cells 
get  folded  and  converge  to  a  central  mass  of  jelly-like  connective 
tissue;  between  the  columns  there  are  septa  of  connective  tissue 
with  blood-vessels  (fig.  557).  The  corpus  luteum  after  a  time  gradu- 
ally disappears ;  but  if  pregnancy  supervenes  it  becomes  larger  and 
more  persistent.  The  following  table  gives  the  chief  facts  in  the 
life-history  of  the  ordinary  human  corpus  luteum,  compared  with 
that  of  pregnancy : — 


Ordinary 
Corpus  Luteum. 


Corpus  Luteum  of 
Pregnancy. 


At  the  end  of 

three  weeks. 

One  month     . 


Two  months 


Six  months 


Nine  months . 


Three-quarters  of  an  inch  in  diameter ;    central  clot  reddish ; 

convoluted  wall  pale. 

Smaller ;    convoluted  wall  j    Larger ;    convoluted  wall  bright 

yellow  ;  clot  still  reddish. 


bright  yellow ;  clot  still 

reddish. 
Reduced  to  the  condition 

of  an  insignificant  cica- 

trix. 
Absent. 


Seven-eighths  of  an  inch  in  dia- 
meter ;  convoluted  wall  bright 
yellow;  clot  decolorised. 

Still  as  large  as  at  end  of  second 
month  ;  clot  fibrinous  ;  convo- 
luted wall  paler. 

One  half  an  inch  in  diameter; 
central  clot  converted  into  a 
radiating  cicatrix  ;  the  external 
wall  tolerably  thick  and  con- 
voluted, but  without  any  bright 
yellow  colour. 


The  ovarian  ovum  or  primary  ob'cyte  (fig.  558)  is  a  large  spheroidal 
cell  surrounded  by  a  transparent  striated  membrane  called  the  zona 


Nucleus  or  germinal  vesicle. 
_^ Nucleolus  or  germinal  spot. 

Space  left  by  retraction  of 
protoplasm. 

'--I Protoplasm  containing  yolk 

spherules. 


Zona  pellucida. 


FIG.  558. — A  human  ovum.    (Cadiat.) 


pellucida,  or    zona  striata.     The   protoplasm    is    filled    with   large 
fatty  and  albuminous  granules  (yolk  spherules),  except  in  the  part 


CH.  LIX.] 


OOGONIA   AND    OOCYTES 


871 


around  the  nucleus,  which  is  comparatively  free  from  them.  It  con- 
tains a  nucleus,  and  usually  one  very  well-marked  nucleolus.  The 
nucleus  and  nucleolus  are  still  often  called  by  their  old  names, 
germinal  vesicle  and  germinal  spot  respectively.  An  attraction 
sphere,  not  shown  in  the  figure,  is  also  present,  and  a  fine  mem- 
brane, the  vitelline  membrane,  immediately  invests  the  protoplasm 
within  the  zona  pellucida. 

The  oocytes  are  developed  from  the  primitive  germ  cells  which 
in  the  earliest  stages  are  interspersed  amid  other  cells  of  the  germinal 
epithelium.  The  primitive  germ  cells  divide  and  produce  oogonia ; 
and  by  the  division  of  the  oogonia,  primary  oocytes  are  formed 
(fig.  559).  The  oogonia  and  primary  oocytes  sink  into  the  stroma, 


FIG.  559. — Diagram  showing  mode  of  development  of  primary  oocytes  from  primitive  germ  cells  iu 
mammalian  ovary.  1,  Germinal  epithelium;  2,  primitive  germ  cells;  3,  oogonia;  4,  primary 
oocytes.  In  A,  two  primitive  germ  cells  are  seen  imbedded  in  the  germinal  epithelium.  In 
B,  a  primitive  germ  cell  has  descended  into  the  stroma  of  the  ovary  accompanied  by  cells  proliferated 
from  the  germinal  epithelium  which  will  become  the  cells  of  the  membrana  granulosa.  In  C,  the 
oogonia  derived  from  primitive  germ  cells,  and  primary  oocytes  produced  by  division  of  the 
oogonia,  are  seen.  (After  Btihler.) 

surrounded  by  cells,  produced  by  the  proliferation  of  the  germinal 
epithelium,  which  are  destined  to  form  the  membrana  granulosa  and 
the  discus  proligerus  of  the  Graafian  follicles. 

The  Fallopian  Tubes  or  oviducts  which  lead  to  the  uterus  have 
externally  a  serous  coat  from  the  peritoneum,  then  a  muscular  coat 
(longitudinal  fibres  outside,  circular  inside),  and  most  internally  a 
vascular  mucous  membrane  thrown  into  longitudinal  folds,  and 
covered  with  ciliated  epithelium. 

The  uterus  consists  of  the  same  three  layers.     The  muscular 


872        REPRODUCTION,  DEVELOPMENT,   GROWTH   AND   DEATH       [CH.  LIX. 

coat  is,  however,  very  thick,  and  is  made  up  of  two  strata  imperfectly 
separated  by  connective  tissue  and  blood-vessels.  Of  these  the 
thinner  outer  division  is  the  true  muscular  coat,  the  fibres  of  which 
are  arranged  partly  longitudinally,  partly  circularly.  The  inner 
division  is  very  thick,  its  fibres  run  chiefly  in  a  circular  direction ; 
the  extremities  of  the  uterine  glands  extend  into  its  internal  surface. 
It  is  in  fact  a  much  hypertrophied  muscularis  mucosse.  The 
mucous  membrane  is  thick  and  consists  of  a  corium  of  soft  con- 
nective tissue, lined  with  ciliated  epithelium;  this  is  continued  down 
into  long  tubular  glands  which  have,  as  a  rule,  a  convoluted  course. 
In  the  cervix  the  glands  are  shorter.  Near  the  os  uteri  the  epi- 
thelium becomes  stratified;  stratified  epithelium  also  lines  the 
vagina. 

THE  PHYSIOLOGY  OF  THE  REPRODUCTIVE  ORGANS 

The  object  of  the  ovary  is  to  produce  ova ;  this  is  known  as 
oogenesis.  The  object  of  the  testis  is  to  produce  spermatozoa ;  this  is 
known  as  spermatogenesis.  The  prodigality  of  nature  in  providing 
for  the  continuance  of  the  species  is  well  illustrated  by  the  fact  that 
at  birth  the  human  ovary  contains  about  70,000  immature  oocytes. 
Quite  a  small  minority  of  these  attain  maturity,  and  get  situated  in 
Graafian  follicles:  many  Graafian  follicles,  moreover,  never  burst; 
after  attaining  a  certain  degree  of  maturity,  even  during  childhood, 
they  atrophy  more  or  less  completely.  On  the  average,  one  Graafian 
follicle  ripens  every  four  weeks,  so  that  in  the  period  between  the 
onset  of  puberty  and  the  menopause,  say  from  fifteen  to  forty-five 
years  of  age,  there  is  a  possibility  in  the  thirty  intervening  years  of 
the  production  of  about  400  ripe  ova.  Of  these  again  a  very  small 
minority  become  fertilised.  Still  more  is  the  lavishness  of  the 
provision  illustrated  in  spermatogenesis ;  it  has  been  calculated  that 
in  the  semen  ejaculated  at  an  act  of  coitus  there  are  more  than  two 
hundred  million  spermatozoa,  and  only  one  of  these  is  needed  for  the 
fertilisation  of  an  ovum. 

Spermatogenesis. — The  spermatozoa  result  from  the  division  of 
the  original  germ  cells,  and  the  stages  which  have  already  been  described 
in  our  account  of  the  structure  of  the  testis  may  bo  represented  in  a 
diagrammatic  form  (see  fig.  560). 

The  germ  cell  divides  into  spermatogonia  which  undergo  several 
divisions,  two  of  which  are  shown  in  the  diagram.  Each 
spermatogonium  in  the  end  grows  and  becomes  a  primary  spermato- 
cyte ;  it  divides  into  two  secondary  spermatocytes,  and  each  of  these 
into  two  spermatids  which  develop  into  spermatozoa.  In  the  division 
of  the  primary  into  the  secondary  spermatocytes,  the  mitosis  is 
heterotype  and  the  number  of  chromosomes  is  reduced  to  half  the 
normal  number.  This  phenomena  is  paralleled  in  the  history  of  the 


CH.  LIX.] 


SPERMATOGENESIS 


873 


oocyte,  and  it  will  be  convenient  to  postpone  the  histological  details 
until  we  come  to  the  oocyte,  where  we  shall  see  a  diagram  to  represent 
the  process. 

The  result  is  that  the  secondary  spermatocyte  and  its  descendants, 
the  spermatids  and  spermatozoa,  have  only  half  the  number  of 
chromosomes  characteristic  of  the  species.  The  maturing  of  a 
spermatozoon  thus  occurs  within  the  seminiferous  tubes. 

Oogenesis. — This  occurs  in  the  same  general  lines  as  spermato- 
genesis,  but  with  some  rather  important  differences  of  detail.  In 


Germ  cell 


Spermatogonia 


Period  of  growth 

Primary  Spermatocyte 


--Secondary  Spermatocytes 


---Spermatids 


Heterotype\ 
mitosis  and  I 
reduction  of  f 
chromosomes  / 
to  half  the 
usual  number) 


A 


•:.TTf, 

+    j    %     ^---Spermatozoa 

Fio.  560. — Diagram  to  illustrate  spermatogenesls. 


the  first  place,  the  changes  in  the  ovary  occur  concurrently  with 
certain  changes  in  the  uterus  which  result  in  menstruation.  A 
second  important  difference  is  that  the  formation  of  the  mature  ovum 
occurs  after  the  ovarian  ovum  has  left  the  ovary,  and  is  on  its  journey 
along  the  Fallopian  tube  to  the  uterus,  previous  to  fertilisation.  A 
third  difference  is  one  of  size,  the  ovum  being  considerably  larger 
than  the  spermatozoon. 

We  will  take  the  phenomenon  known  as  menstruation  first.  On 
the  average  once  every  four  weeks  the  uterus  becomes  congested, 
and  its  mucous  membrane  thickened;  finally  some  of  the  blood- 


874         REPRODUCTION,   DEVELOPMENT,    GROWTH   AND   DEATH       [CH.  LIX. 

vessels  of  the  mucous  membrane  rupture  and  the  escaping  blood 
together  with  the  secretion  of  the  uterine  glands,  and  some  epithelial 
debris  from  the  surface  constitutes  the  monthly  or  menstrual  flow. 
The  amount  of  destruction  of  the  mucous  membrane  varies  a  good 
deal,  but  it  usually  involves  not  only  the  surface  epithelium,  but 
extends  into  the  interglandular  tissue.  The  flow  lasts  for  three  or 
four  days,  and  the  amount  of  blood  lost  may  be  as  much  as  300  c.c. 
After  the  cessation  of  the  flow,  the  mucous  membrane  repairs  itself ; 
this  takes  about  a  fortnight,  and  then  after  a  brief  period,  generally 
not  more  than  a  few  days,  preparation  for  the  next  menstrual  epoch 
begins  once  more.  These  phenomena  are  accompanied  with  a  feeling 
of  malaise,  and  in  some  cases  with  more  or  less  pronounced  pain. 

Menstruation  is  absent  during  pregnancy,  and  as  a  rule  also 
during  the  subsequent  period  of  lactation. 

There  is  no  doubt  that  this  uterine  phenomenon  is  related  to 
ovulation  (that  is,  the  discharge  of  ova  from  the  ripe  follicles) ;  for 
menstruation  begins  at  puberty  when  ovulation  starts,  and  ceases  to 
occur  at  the  menopause  when  ovulation  ceases  ;  an  artificial  menopause 
may  be  created  by  removal  of  the  ovaries,  and  in  certain  cases  it  has 
been  claimed  that  menstruation  was  resumed  after  an  ovary  had  been 
transplanted  back  again.  This  looks  as  if  the  relationship  is  not 
a  nervous  one.  Moreover  the  monthly  periodicity  is  the  same  in 
both  processes.  The  period  of  sexual  activity  varies  greatly  in 
different  animals;  in  some  of  the  monkeys  the  monthly  period 
occurs  as  in  the  human  female ;  but  in  many  of  the  lower  animals 
the  times  of  sexual  activity  and  sexual  desire  are  much  more  widely 
separated.  In  animals  such  times  are  known  popularly  as  heat  or 
rut,  and  technically  as  the  oestrus.  It  is  the  pre-oastral  period  in 
animals  which  is  homologous  with  menstruation,  while  oestrus  is  the 
period  of  sexual  desire,  when  coitus  may  occur. 

Although  there  is  no  doubt  of  the  relationship  between 
ovulation  and  menstruation,  there  has  been  much  discussion  as  to 
which  occurs  first.  But  in  animals,  where  the  phenomena  of  the 
pre-cestral,  oestral,  and  post-oestral  periods  can  be  followed  more 
easily,  there  is  no  doubt  that  ovulation  occurs,  or  the  ova  reach 
maturity  after  or  at  the  very  end  of  the  uterine  flow ;  that  is  to  say, 
ovulation  takes  place  during  oestrus  and  not  during  the  pre-oestral 
period,  which  is  the  homologue  of  menstruation.  This  has  been 
shown  more  particularly  in  the  case  of  the  dog,  the  sheep,  and 
the  pig. 

Many  more  or  less  fantastic  theories  have  in  the  past  been  put 
forward  to  explain  menstruation.  There  is,  however,  but  little 
doubt  that  its  object  is  the  preparation  of  the  uterine  lining  for  the 
reception  of  an  ovum,  either  because  a  monthly  regeneration  main- 
tains it  in  a  condition  of  irritability  which  enables  it  to  respond 


CH.  LIX.] 


MATURATION   OF  THE  OVUM 


875 


promptly  to  the  stimulus  of  an  ovum  by  the  formation  of  a  decidua, 
or  as  Pfliiger  taught,  because  it  provides  a  raw  surface  on  which  the 
ovum  is  easily  grafted. 

The  ovum,  after  it  is  liberated  from  the  ovary  by  the  rupture  of 
a  Graafian  follicle,  enters  the  Fallopian  tube,  the  cilia  on  the 
fimbrise  of  which  are  the  main  instruments  for  the  transportation. 
It  travels  along  the  Fallopian  tube,  and  finally  reaches  the  uterus, 
and  again  this  is  accomplished  by  ciliary  action.  During  this 
journey,  which  probably  occupies  some  days,  it  becomes  mature,  it 
is  fertilised,  and  some  of  the  early  steps  in  further  development 
may  also  occur. 

Maturation  of  the  Ovum. — We  have  already  seen  that  the  germ 
cells  which  form  the  ova  are  at  first  imbedded  in  the  germinal 


Fro.  561.— Diagram  showing  the  formation  of  the  polar  bodies  (maturation  of  the  ovum).  A,  B,  and  C 
show  stages  in  the  formation  of  the  first  polar  body  by  heterotype  mitosis.  A  is  a  primary 
oiicyte  at  the  commencement  of  mitosis,  when  only  half  the  usual  number  of  chromosomes 
appear.  C  is  a  secondary  oiicyte ;  it  has  no  distinct  nucleus,  because  no  resting-stage  occurs  ;  after 
the  separation  of  the  first  polar  body,  the  chromosomes  which  remain  in  the  secondary  oiicyte  at 
once  rearrange  themselves  on  a  new  spindle.  D  is  the  mature  ovum,  with  the  female  pronucleus 
and  the  two  polar  bodies.  1,  First  polar  bud;  2,  first  polar  body;  8,  second  polar  body;  4, 
chromosomes  on  spindle  of  primary  oiicyte;  5,  zona  striata ;  6,  viielline  membrane;  7,  daughter 
chromosomes  in  first  polar  bud ;  8,  female  pronucleus. 

epithelium,  from  which  they  pass  into  the  stroma  of  the  ovary,  and 
then  by  division  and  growth  they  form  oogonia ;  from  the  oogonia, 
primary  oocytes  are  developed,  and  these  become  enclosed  in  Graafian 
follicles.  The  process  by  which  the  primary  oocytes  become  con- 
verted into  mature  ova  is  known  as  maturation;  this  consists 
essentially  of  a  double  mitotic  division  of  the  oocyte,  each  division 
producing  two  unequal  parts.  The  first  division  produces  a  secondary 
oocyte  and  the  first  polar  body ;  the  second  division,  which  takes  place 


876    REPRODUCTION,  DEVELOPMENT,  GROWTH  AND  DEATH   [CH.  LIX. 

without  any  resting-stage,  results  in  the  formation  of  the  mature 
ovum  and  the  second  polar  body.  Thus,  when  the  two  divisions  are 
completed,  the  mature  ovum  and  two  polar  bodies  lie  inside  the 
zona  pellucida. 

The  unequal  division  is  associated  with  an  eccentric  position 
of  the  spindle.  At  each  division  one  end  of  the  spindle  projects 
on  the  surface  with  a  little  surrounding  protoplasm,  and  it  is  this 
small  nodule  which  becomes  the  polar  body  (see  fig.  561). 

One  of  the  essential  features  of  this  maturation  is  the  halving  of 
the  number  of  chromosomes  in  the  nucleus.  When  maturation  com- 
mences in  the  primary  oocytes,  an  achromatic  spindle  is  formed  in 
the  usual  way ;  but  instead  of  the  ordinary  number  of  chromosomes 
appearing  at  its  equator,  only  half  that  number  are  seen:  for 
example,  if  eight  be  the  normal  number  of  chromosomes,  only  four 
appear.  Further,  each  chromosome  is  not  a  slender  V-shaped  loop, 
but  a  short,  thick  rod,  or  ring,  or  group  of  four  particles.  Neither 


2a 


2  02 

Pio.  562.— Diagram  showing  the  stages  in  the  maturation  of  the  ovum  when  the  first  polar  body 
divides.  1,  Primary  oocyte;  2,  secondary  oocyte;  2a,  first  polar  body;  3,  mature  ovum;  3a, 
second  polar  body  ;  2al,  and  2a2,  daughter  cells  of  the  first  polar  body. 

does  it  split  longitudinally  in  the  usual  way,  but  transversely ;  and  at 
the  end  of  the  process  the  secondary  oocyte  and  the  first  polar  body 
both  contain  four  chromosomes.  This  form  of  mitosis  is  known  as 
heterotype,  in  contradistinction  to  the  ordinary  form  which  is  called 
Jiomotype.  The  second  division  which  produces  the  mature  ovum 
and  the  second  polar  body  is  homotype,  and  the  final  result  is  that 
each  of  the  segments  into  which  the  primary  oocyte  divides  contains 
half  the  number  of  chromosomes  present  in  the  parent  germinal 
cell.  In  some  cases,  the  first  polar  body  divides  at  the  same  time 
that  the  second  polar  body  is  formed;  the  whole  process  is  repre- 
sented in  the  schema  in  fig.  562.  The  nucleus  of  the  mature  ovum 
is  known  as  the  female  pronucleus. 

It  should  be  added  that  the   mature   ovum   is   destitute   of  a 
entrosome ;  that  is  lost  with  the  formation  of  the  polar  bodies. 


CH.  LIX.] 


OOGENESIS 


877 


We  are  now  in  a  position  to  construct  a  diagram  similar  to  that 
in  fig.  560,  which  represents  the  history  of  the  male  reproductive 
element.  The  history  of  the  female  element  from  the  original  germ 
cell  is  shown  in  fig.  563. 

As  in  the  male  the  germ  cell  divides  and  subdivides,  and  in  this 
way  successive  generations  of  oogonia  are  produced ;  two  of 
the  subdivisions  are  shown  in.  the  diagram.  Each  oogonium  then 
grows,  and  becomes  a  primary  oocyte,  which  is  the  ovarian  ovum 


Germ  cell 


Oogonia 

-  -  Period  of  growth 
Primary  oocyte 

-First  polar  body 


j  Division  of  the 
I  First  Polar  body 


Second  polar  body 


Heterotype  mitosis 
and  reduction  of  the 
chromosomes  to  half 
the  usual  number 


Secondary  oocyte 


Mature  ovum 


FIG.  563. — Diagram  to  illustrate  oogenesis. 

within  the  Graafian  follicle.  Its  maturation,  which  occurs  outside 
the  ovary,  is  represented  in  the  lower  part  of  the  diagram,  which  is  a 
repetition  of  what  is  also  seen  in  fig.  562. 

Each  primary  spermatocyte  gives  rise  to  four  spermatozoa  of 
equal  value.  Each  primary  oocyte  gives  rise  to  four  cells,  which  are 
of  unequal  value ;  one  of  these  is  the  mature  ovum,  the  other  three 
are  the  minute  polar  bodies  which  may  be  regarded  as  abortive  ova. 
The  mitosis  which  results  in  the  halving  of  the  normal  number  of 
•chromosomes  occurs  in  each  sex  at  the  same  stage,  namely,  in  the 
formation  of  the  secondary  spermatocyte,  and  of  the  secondary 
oocyte  respectively. 


878    KEPRODUCTION,  DEVELOPMENT,  GROWTH  AND  DEATH   [CH.  LIX. 

The  meaning  of  the  polar  bodies  has  been  the  subject  of  much  speculation ;  it 
is  supposed  that  the  female  cell  casts  out  certain  constituents  in  order  to  make 
room  for  the  addition  to  it  of  material  from  another  individual,  namely,  the  male. 
Some  animals  multiply  without  the  intervention  of  the  male  sex,  or  the  intervention 
occurs  at  long  intervals  with  many  intermediate  generations  ;  this  is  known  as 
parthenogenesis.  One  must  therefore  suppose  that  the  female  cell  has  within  it  a 
male  component  which  can  be  transmitted  to  future  generations.  The  ovum  of 
these  animals  only  extrudes  one  polar  globule.  It  may  therefore  be  that  the 
second  polar  body  contains  the  hereditary  male  element  which  is  retained  in 
parthenogenesis,  but  in  animals  which  multiply  sexually  this  is  got  rid  of  prior 
to  the  inception  of  the  new  male  element. 

This  brings  us  to  the  stage  in  our  story  when  both  male  and 
female  elements  are  ripe  and  ready  for  union.  Logically  we  should 
next  study  how  the  union  is  accomplished.  But  first  we  must  step 
into  a  bye-path,  and  before  leaving  the  ovary  and  testis  enquire 
whether  these  organs  have  any  other  functions  than  those  we  have 
already  discussed.  This  may  best  be  done  under  the  following  new 
heading. 

INTERNAL  SECRETIONS  OF  OVARY  AND  TESTIS 

The  operation  of  castration,  that  is,  the  removal  of  the  essential 
generative  organs,  naturally  leads  to  a  loss  of  reproductive  power, 
but  it  has  other  effects  of  a  more  general  kind  on  the  organism, 
which  mainly  influence  what  are  known  as  the  secondary  sexual 
characters.  This  effect  is  believed  to  be  due  to  the  lack  of  certain 
internal  secretions  formed  by  testis  and  ovary  respectively. 

Testis. — Some  years  ago  Brown-Sequard,  then  an  old  man  of 
seventy-two,  stated  that  the  subcutaneous  injection  of  testicular 
extracts  into  himself  produced  marked  rejuvenating  effects.  More 
recently  Poehl  has  described  the  beneficial  stimulating  effects  of  a 
substance  prepared  from  the  testis,  which  he  terms  spermine.  He 
has  assigned  to  it  the  formula  C5H14N2,  but  Dixon  has  shown  that 
it  is  a  mixture  of  proteins  with  other  organic  and  inorganic  materials. 
The  supposed  tonic  effects  of  such  injections  are  regarded  with 
great  suspicion,  and  temporary  benefit,  if  it  does  occur,  is  mainly 
attributable  to  suggestion. 

The  principal  evidence  upon  which  the  assumption  rests  that  the 
testis  forms  an  internal  secretion,  is  derived  from  the  effects  of 
castration,  or  from  cases  in  which  the  testes  do  not  descend  into  the 
scrotum.  If  the  operation  of  castration  is  performed  before  puberty, 
the  reproductive  apparatus  which  is  left  (vesiculse  seminales  and 
prostate,  but  not  the  penis)  atrophy ;  the  secondary  sexual  characters 
(growth  of  hair  on  the  face,  deepening  of  the  voice,  etc.)  do  not 
develop ;  the  body  remains  infantile,  but  never  assumes  female 
characters.  The  body,  however,  grows,  and  in  some  cases  there  is 
overgrowth  of  the  skeletal  and  adipose  tissues. 

In  animals  there  is  corroborative  evidence  of  the  same  nature. 


CH.  LIX.]  SECONDARY    SEXUAL   CHARACTERS  879 

Thus  in  the  cock  castration  arrests  the  development  of  the  comb  and 
spurs  ;  in  the  stag  of  the  antlers.  In  the  eland  and  in  horned  cattle 
where  both  sexes  have  horns,  their  growth  is  not  inhibited  by 
castration,  though  their  shape  may  be  affected  (Marshall).  In 
Herdwick  sheep,  where  the  males  are  horned  and  the  females  horn- 
less, it  has  been  shown  that  the  presence  of  the  testes  is  essential, 
not  merely  for  the  initiation  but  also  for  the  continuance  of  horn 
growth.  Castration  stops  further  horn  growth  forthwith,  and  at 
every  stage  of  development. 

Ligature  of  the  vas  deferens  leads  to  atrophy  of  the  seminiferous 
tubules,  whilst  the  interstitial  cells  are  not  affected,  and  the 
secondary  sexual  characters  develop  as  usual.  It  is  on  this  ground 
that  most  investigators  agree  that  the  interstitial  cells  of  the  testis 
are  the  source  of  the  internal  secretion.  These  cells  have  all  the 
appearances  of  secreting  cells,  and  their  full  development  coincides 
with  the  first  appearance  of  spermatogenesis.  Transplantation  of  a 
testis  in  an  abnormal  position  in  the  body  cavity  is  followed  by 
development  of  the  secondary  sexual  characters,  and  the  view  is 
generally  held  that  the  internal  secretion  acts  chemically  on  the 
parts  concerned,  rather  than  through  the  intermediation  of  the 
nervous  system. 

The  Prostate. — As  already  stated,  the  removal  of  the  testis  leads  to  atrophy  of 
the  prostate,  but  the  converse  has  been  stated  to  be  also  true,  and  that  in  dogs 
prostatectomy  causes  the  testes  to  lose  their  functional  activity.  Attempts  to 
repeat  these  effects,  by  other  observers,  have,  however,  failed,  and  as  Marshall 
points  out,  it  is  unlikely,  on  phylogenetic  grounds,  that  the  functions  of  the 
essential  reproductive  organ  should  depend  upon  the  presence  of  an  accessory 
gland  of  comparatively  late  appearance  in  the  history  of  evolution. 

The  Ovary. — Extirpation  of  the  ovaries  prevents  the  onset  of 
puberty  and  the  occurrence  of  menstruation,  but  produces  no 
noticeable  effects  on  the  general  form  and  appearance  of  a  woman. 
Ovariotomy  after  puberty  brings  menstruation  to  an  end,  and  there 
may  be  slight  atrophy  of  the  breasts,  uterus,  and  external  genital 
organs ;  this,  however,  does  not  always  occur. 

In  animals  the  same  operation  prevents  the  occurrence  of  the 
cestral  cycle,  but  the  "  periods  "  continue  to  recur  if  one  of  the  ovaries 
is  grafted  into  the  abdomen. 

The  ovary  does  not  appear  to  have  such  far-reaching  effects  on 
general  metabolism  as  the  testis  possesses;  its  internal  secretion 
seems  to  act  especially  upon  the  uterus.  Marshall's  observations 
on  dogs,  and  Heape's  on  monkeys,  favour  the  view  that  the 
interstitial  cells  of  the  ovary  are  responsible  for  the  production  of  a 
hormone  which  initiates  the  cestrous  cycle,  and  if  this  is  the  case  the 
occurrence  of  menstruation  in  the  human  female  is  attributable  to 
the  action  of  the  same  cells. 


880    REPRODUCTION,  DEVELOPMENT,  GROWTH  AND  DEATH   [CH.  LIX. 

The,  Corpus  Luteum. — Special  interest  attaches  to  the  function 
of  the  corpus  luteum  which  is  formed  in  the  Graafian  follicle  after 
the  exit  of  the  ovum.  We  have  already  seen  that  this  structure 
attains  a  great  size  if  pregnancy  ensues.  The  luteal  cells  are  formed 
from  the  lining  cells  of  the  follicle  and  not  from  the  interstitial  cells 
just  alluded  to.  It  has  been  generally  assumed  that  the  corpus  luteum 
forms  a  hormone  or  hormones,  and  the  functions  which  have  been 
assigned  to  these  chemical  messengers  are  four  in  number. 

1.  To  affect  the  uterus  and  bring  about   there   the   cestrous   or 
menstrual  cycle.     This  view  may  be  dismissed  at  once ;  the  hypothesis 
is  negatived,  first,  because  it  does  not  explain  the  occurrence  of  the 
first   oestrous   cycle  in   the   young  animal,   and    secondly,   because 
injection  of  luteal  extracts  does  not  induce   uterine   changes.     The 
cells  concerned  in  that  function  are,  as  already  stated,  the  interstitial 
ovarian  cells. 

2.  To  inhibit  the  ripening  of  Graafian  follicles  during  pregnancy 
(Loeb).     This  may  be  an  effect,  but  it  is  hardly  a  function. 

3.  To  assist  in  some  way  the  fixation  and  early  development  of 
the  impregnated  ovum  in  the  uterus.     This  view  is  much  favoured 
by  most  authorities,  and  the  principal  evidence  in  its  favour  is  that 
removal  of  the  ovaries,  or  even  destruction  of   the   corpus   luteum 
shortly  after  pregnancy  has  begun,  brings  that  process  to  an  end ; 
the   same   operation   later   in   pregnancy  has   no   effect   upon   the 
development  of  the  foetus  or  the  subsequent  act  of  parturition. 

4.  To  stimulate  the  growth  of  the  mammary  glands  during  the 
early  months   of  pregnancy.      Prolonged  search  for  the  secretory 
nerves   of  the  milk  glands  have   failed   to   reveal   their   presence. 
Cases    have    occurred    in   which    severe    injuries    to   the   nervous 
system    preclude    any    possible    nervous   connection    between   the 
generative    organs    and    the   mammary  glands;    nevertheless,    the 
latter   grow   and    ultimately  produce   milk.      Such    considerations 
point    to    the    conclusion    that   the   correlation   must   be   chemical 
rather    than    nervous.       A    few    years     ago    Starling    and    Miss 
Lane   Claypon   thought   that   the   hormone   in    question    must    be 
secreted  by  the  foetus,  because  the  injection  of   foetal   extracts   in 
rabbits  led  to  a  hypertrophy  of  the  mammary  tissue.     The  hyper- 
trophy, however,  is  imperfect,  and  doubt  was  felt  in  many  quarters 
whether  this  could   be  the  whole   explanation,  because   mammary 
evolution  occurs  in  many  virgin  animals  in  which  ovulation  is  not 
followed  by  pregnancy ;  moreover,  in  many  cases  enlargement  of  the 
breasts  occurs  at  each  menstrual  epoch.     The  view  is  now  advanced 
that  a  hormone  is  secreted  by  the  corpus  luteum,  which  is  an  inciting 
cause  of  the  early  growth  of  mammary  tissue.      The  close  corre- 
spondence between  the  stages  in   the   development   of   the   corpus 
luteum  and  of  the  mammary  glands  has  been  clearly  brought  out 


CH.  LIX.]  FERTILISATION  .  881 

by  the  recent  work  of  O'Donoghue.  One  must,  however,  point  out 
that  as  a  rule  there  is  no  corpus  luteum  in  the  ovaries  during 
menstruation,  or  during  the  pre-oestral  period  in  sows,  when  the 
mammary  glands  show  signs  of  growth  and  congestion. 

The  therapeutic  use  of  ovarian  extracts  appears,  from  the  evidence  available, 
to  stand  in  the  same  uncertain  position  as  that  of  testicular  extracts. 

If  the  reader  refers  back  to  the  chapter  on  the  ductless  glands  he  will  find 
that  some  of  these  (thymus,  pituitary,  etc.)  influence  the  formation  of  the  genera- 
tive organs. 

The  structure  of  the  mammary  glands  and  the  composition  of  milk  have 
already  been  treated  at  length  in  our  chapter  on  Foods  (see  pp.  481-486). 

FERTILISATION 

"We  are  now  in  a  postion  to  resume  the  thread  of  the  history  of 
the  further  development  of  a  new  individual.  The  next  step  is  the 
union  of  the  male  and  female  gametes,  that  is  to  say,  of  the 
spermatozoon  and  the  mature  ovum. 

The  act  of  coitus  or  copulation  is  associated  in  both  sexes  with 
much  psychical  excitement,  and  with  the  phenomenon  of  erection 
(see  p.  313).  The  spermatozoa  are  thus  deposited  at  the  entrance  of 
the  uterus,  and  by  means  of  the  flagellar  movement  of  their  tails 
they  make  their  way  against  the  stream  of  ciliary  movement  into 
the  Fallopian  tubes,  where  they  are  found  in  a  living  condition  for 
many  days.  It  is  here  that  they  meet  the  mature  ovum;  but 
fertilisation  or  impregnation  only  requires  the  entrance  of  one 
spermatozoon  into  the  ovum.  By  means  of  its  sharp  head 
cap  the  spermatozoon  pierces  the 

zona    pellucida,   and    the    head,  ^ ^~ ZONA  PELLUCIDA 

neck,  and  possibly  part  of  the 
body,  enter  the  substance  of  the 
ovum,  where  they  undergo  trans- 
formation, and  are  converted 
into  a  male  pronucleus  with  an 
attendant  attraction  sphere  and 
its  centrosome.  The  male  pro- 
nucleus  contains  the  same  number 
of  chromosomes  as  the  female 
pronucleus,  for  the  mitosis  which  FIQ  564-_T1^-^d  ova  or  blastosphere) 

OCCUrS    when     the    primary     Sper-  showing    its    new    nucleus    and    attraction 

. .     .  ,  «  __         >  spheres ;  the  yolk  granules  have  been  omitted. 

matocyte   divides   to   form    two 

secondary  spermatocytes,  is  a  heterotype  mitosis,  in  which  only 
half  the  usual  number  of  chromosomes  appear;  and  consequently 
the  secondary  spermatocytes,  and  their  descendants  the  spermatids, 
also  contain  only  half  the  typical  number  of  chromosomes.  These 
are  retained  in  the  spermatozoa,  which  are  produced  by  modifica- 
tion of  the  spermatids,  and  they  reappear  in  the  male  pronucleus. 

3  * 


882         REPRODUCTION,  DEVELOPMENT,   GROWTH   AND   DEATH       [CH.  LIX. 

After  the  male  pronucleus  has  formed  in  the  substance  of  the 
mature  ovum,  it  approaches  the  female  pronucleus,  and  when  the 
two  pronuclei  fuse,  fertilisation  is  completed.  The  nucleus  which 
results  from  the  fusion — the  first  segmentation  nucleus — contains 
the  typical  number  of  chromosomes,  half  being  derived  from  the  female 
and  half  from  the  male  germinal  element.  When  the  fertilisation  is 
completed,  the  segmentation  nucleus  is  accompanied  by  two  attrac- 
tion spheres  with  their  centrosomes  (see  fig.  564) ;  one  of  these  spheres 
is  introduced  with  the  male  pronucleus,  and  the  other  probably 
originates  from  it  by  division,  since  the  centrosome  of  the  ovum  is 
lost  during  maturation. 

Loeb  has  suggested  that  the  action  of  the  spermatozoon  is 
essentially  chemical,  because  in  certain  invertebrate  animals  (for 
instance,  sea  urchins)  he  has  been  able  to  produce  artificial  partheno- 
genesis by  purely  chemical  methods.  In  his  latest  work,  he  placed 
the  ova  in  dilute  acetic  or  formic  acid ;  by  this  means,  a  membrane 
is  formed  upon  the  surface  of  the  egg-cell  as  it  is  in  normal 
fertilisation;  if  the  ova  are  then  transferred  to  concentrated  sea 
water  for  a  short  time  and  then  placed  in  ordinary  sea  water,  they 
segment  and  produce  normal  larvae.  He  considers  that  the  sperma- 
tozoon brings  with  it  enzymes  or  other  chemical  substances  which 
excite  the  ovum  in  the  same  way  as  the  chemical  reagents  mentioned. 

The  changes  by  which  the  fertilised  ovum  is  transformed  into 
the  young  animal  may  take  place  either  inside  or  outside  the 
body  of  the  parent.  If  they  take  place  inside  the  parent,  as  in 
mammals,  including  the  human  subject,  the  ovum  is  small,  and 
the  nutriment  necessary  for  its  growth  and  development  is  derived 
from  the  surrounding  tissues  and  fluids  of  the  mother.  If  the 
development  takes  place  outside  the  parent's  body,  as  in  birds,  the 
egg  is  larger;  it  contains  a  large  amount  of  nutritive  material 
called  the  yolk,  and  it  may,  in  addition,  be  surrounded  by  sheaths  of 
nutritive  substance.  Thus,  in  the  hen's  egg,  the  yellow  part  alone  is 
comparable  with  the  mammalian  ovum,  and  the  larger  part  of  that 
is  merely  nutritive  substance.  Upon  the  yolk  is  a  whitish  speck,  the 
cicatricula,  which  is  a  small  mass  of  protoplasm,  about  J  of  an  inch 
in  diameter.  In  the  cicatricula  lies  the  nucleus  or  germinal  vesicle, 
and  it  is  this  small  mass  of  protoplasmic  substance  which  divides 
and  grows  to  produce  the  chick ;  the  yolk  and  the  surrounding  white 
being  used  as  food. 

Ova  such  as  the  hen's,  in  which  only  a  small  part,  the  cicatricula, 
divides  and  grows,  are  called  meroblastic.  Small  ova,  with  little  food 
yolk,  such  as  the  human  ovum,  divide  completely  during  develop- 
ment, and  are  called  holoblastic,  but  numerous  gradations  occur 
between  the  two  extreme  types. 

The  further  development  of  the  individual  systems  of  organs  by 


CH.  LIX.] 


SEGMENTATION 


883 


which  the  embryonic  rudiments  are  converted  into  the  more  fully 
developed  condition  in  which  they  are  found  at  birth  is  a  subject 
fully  treated  in  works  on  anatomy,  embryology,  and  obstetrics,  and  we 
shall  not  go  into  those  matters  here.  The  nutrition  of  the  embryo 
and  the  circulation  of  its  blood  are,  however,  matters  of  physiological 
moment,  so  that  it  will  be  necessary  to  refer  to  the  origin  of  the 
foetal  membranes,  as  it  is  by  their  means  that  nutrition  is  carried  on. 
Let  us,  however,  first  briefly  take  up  the  early  stages  in  development. 

SEGMENTATION 

After  fertilisation  is  completed,  the  ovum  divides  into  two  parts ; 
each  of  these  again  divides,  and  so  on  till  a  mulberry-shaped  mass — 
the  morula — is  formed.  It  consists  of  a  large  number  of  small  cells 
and  it  is  enclosed  together  with  the  polar 
bodies,  in  the  zona  pellucida.  The  polar 
bodies  soon  disappear ;  indeed  in  many  cases 
they  have  vanished  long  before  the  morula 
is  completed.  A  cavity  soon  appears  in  the 
morula,  which  thus  becomes  converted  into 
a  blastula  or  blastocyst.  The  cells  which 
form  the  peripheral  wall  of  the  blastula 
assume  a  more  or  less  cubical  form,  whilst 
those  which  lie  in  the  interior  and  form  the 
inner  cell  mass  are  irregular  in  outline,  and 
they  are  grouped  together  at  one  pole  of  the 
blastula  (see  figs.  566,  567).  At  this  period 
the  blastula  is  unilaminar,  except  at  the 
region  where  the  inner  cell  mass  is 
situated;  but  soon  the  cells  of  the  inner 
mass  extend  round  the  cavity  and  the  wall 
of  the  cyst  becomes  bilaminar,  the  outer 
layer  being  called  epiblast  and  the  inner 
hypollast.  A  little  later  the  mesoblast  or 
third  layer  of  the  blastoderm  grows  and 
extends  between  the  epiblast  and  hypoblast 
over  the  whole  area  of  the  vesicle. 

That  portion  of  the  mesoblast  which  lies 
immediately  at  the  sides  of  the  neural 
groove  becomes  partially  separated  from  the 
rest,  and  at  the  same  time  divided  into 
cuboidal  blocks,  the  protovertebrse  or  meso- 
blastic  somites  (see  also  fig.  570).  The  more 
laterally  situated  part  of  the  mesoblast 

constitutes  the  lateral  plates,  and  the  narrow  strand  of  meso- 
blastic  cells  which  connects  the  lateral  plate  on  each  side  with  the 


FIG.    565.  —  Diagrams 


tin- 


early  stages  of  cleavage  of  the 
ovum.    (Dal ton.) 


884        EEPRODUCTION,  DEVELOPMENT,   GROWTH   AND   DEATH      [CH.  LIX. 

protovertebral  somites  is  the  intermediate  cell  mass.  Soon  after  its 
formation  the  lateral  mesoblast  is  cleft  into  two  layers,  and  the  space 
which  appears  between  the  two  layers  is  called  the  coelom  (figs.  568, 
569).  The  outer  or  somatic  layer  of  the  mesoblast  adheres  to  the 
epiblast;  the  two  together  form  the  somatopleur.  The  inner  or 
splanchnic  layer  fuses  with  the  hypoblast  to  form  the  splanchnopleur. 


FIG.  565.— Diagram  of  a  surface 
view  of  a  young  mammalian 
blastula.  1,  Germinal  area. 
A,  line  of  section  represented 
in  fig.  567. 


Flo.  567. —7  Diagram  of  a 
section  of  the  mammalian 
blastula  shown  in  fig.  566 
along  the  line  A.  1,  Ger- 
minal area  ;  2,  epiblast ; 
3,  inner  cell  mass. 


Whilst  the  mesoblast  is  extending  and  cleaving,  the  neural  ridges, 
which  are  longitudinal  epiblastic  upgrowths  on  each  side  of  the 
middle  line,  gradually  grow  in  height,  and  their  free  margins  turn 
inwards  and  fuse  together.  This  fusion  commences  in  the  cervical 
region,  and  extends  forwards  and  backwards,  and  when  it  is  com- 
pleted the  neural  groove  is  converted  into  a  closed  tube,  the  neural 


6 


FIG.  568. — Diagram  of  a  transverse  section 
through  a  mammalian  blastoderm  after  the 
formation  of  the  three  primary  layers.  1, 
Primitive  groove ;  2,  primitive  streak ;  3, 
epiblast;  4,  mesoblast;  5,  hypoblast;  6, 
coelom ;  7,  archenteron. 


7    B 


FIG.  569. — Diagram  of  a  transverse  section 
through  a  mammalian  blastoderm,  show- 
ing the  neural  ridges.  1,  Neural  groove  ; 
2,  neural  ridge ;  8,  epiblast ;  4,  somatic 
mesoblast ;  5,  splanchnic  mesoblast ;  6, 
hypoblast ;  7,  somatopleur ;  8,  splanch- 
nopleur; 9,  notochord  ;  10,  ccelom;  11, 
archenteron. 


canal,  which  is  the  central  canal  of  the  nervous  system.  In  the 
embryo  at  this  period  there  are,  therefore,  three  cavities :  (1)  The 
neural  canal  lined  by  epiblast ;  (2)  The  coelom  or  space  in  the  meso- 
blast; (3)  The  archenteron  within  the  hypoblast.  While  these 
changes  are  in  progress  the  embryonic  area  begins  to  fold  off  from 
the  rest  of  the  embryo.  A  sulcus  appears  all  round  the  margins 
of  the  area,  and  over  this  sulcus  the  area  bends  forwards,  backwards, 


CH.  LIX.] 


EAELY  FCETAL  STRUCTURES 


885 


S.O 


and  laterally.     It  looks  as  if  some  constricting  agent  had  been  placed 

round  the  margin  of  the  area,  and  that  afterwards  the  area  above 

the  constriction,  and  the  area  below  had 

gone  on  growing  rapidly.     In  this  way, 

the  embryo  is  clearly  separated  into  two 

parts,  an  upper,  the  foetus,  and  a  lower, 

which   becomes    the    appendages    of    the 

foetus.*     The  anterior  part  of  the  folded 

embryonic  area  is  known  as  the  head  fold, 

the  posterior  as  the  tail  fold,  and  the  two 

are  connected  together  on  each  side  by  the 

lateral  folds. 

The  portion  of  the  archenteron  en- 
closed in  the  foetus  forms  the  primitive 
gut.  The  part  contained  in  the  head  fold 
is  the  fore-gut,  that  in  the  tail  fold  is  the 
hind-gut,  and  the  remainder  is  the  mid- 
gut  (fig.  572). 

The  constriction  where  the  body  of  the 
foetus  becomes  continuous  with  the  re- 
maining structures,  is  known  ultimately 
as  the  umbilicus.  It  remains  pervious  till 
birth,  and  through  it  the  mid-gut  is 
connected  with  the  remainder  of  the 
archenteron  (which  is  henceforth  called 
the  yolk-sac)  by  a  narrow  hypoblastic 
tube,  the  vitello-intestinal  duct  (fig.  571, 
10). 

The  portion  of  the  mesoblastic  cavity 
enclosed  in  the  foetus  is  called  the  body 
cavity.  It  gradually  differentiates  into  the 
pericardial,  pleural  and  peritoneal  cavities, 
which  are  eventually  entirely  separated 
from  one  another. 

Before  the  neural  groove  is  closed  and 
becomes  the  neural  canal,  the  hypoblast 
beneath  the  middle  of  the  groove  becomes 
thickened  to  form  a  longitudinal  ridge 
(fig.  569).  This  ridge  is  the  notochord  or 


pr 


FIG.  570.— Embryo  chick  (86  hours), 
viewed  from  beneath  as  a  trans- 
parent  object  (magnified),  pi,  Out- 
line of  pellucid  area ;  FB,  fore-brain, 
or  first  cerebral  vesicle :  from  its 
sides  project  op,  the  optic  vesicles  ; 
SO,  backward  limit  of  somatopleur 
fold,  "tucked  in"  under  head; 
a,  head  fold  of  true  amnion ;  a',  re- 
flected layer  of  amnion,  sometimes 
termed  "  false  amnion  " ;  sp,  back- 
ward limit  of  splanchnopleur  folds, 
along  which  run  the  omphalo- 
mesenteric  veins  uniting  to  form 
h,  the  heart,  which  is  continued 
forwards  into  la,  the  bulbus  arte- 
riosus ;  d,  the  fore-gut,  lying  behind 
the  heart,  and  having  a  wide  cres- 
centic  opening  between  the  splanch- 
nopleur folds  ;  HB,  hind-brain  ; 
MB,  mid-brain  ;  pv,  protovertebrae 
lying  behind  the  fore-gut ;  me,  line 
of  junction  of  medullary  folds  and 
of  notochord ;  ch,  front  end  of  noto- 
chord ;  vpl,  vertebral  plates ;  pr, 
the  primitive  groove  at  its  caudal 
end.  (Foster  and  Balfour.) 


*  Among  many  anatomists  and  obstetricians 
the  word  ovum  is  applied  to  the  foetus  and  its 
appendages.  It  should  be  properly  restricted  to 
the  female  gamete.  After  development  has  com- 
menced the  term  embryo  should  be  employed,  and  that  word  includes  the  embryo 
proper  which  we  call  the  foetus,  and  its  appendages. 


886         REPKODUCTION,    DEVELOPMENT,    GKOWTH   AND   DEATH       [CH.  LIX. 


primitive  skeletal  axis.  It  soon  separates  from  the  remainder  of  the 
hypoblast,  and  forms  a  round  cord,  which  lies  at  first  immediately 
beneath  the  neural  groove,  and  afterwards  beneath  the  neural  tube, 
extending  from  the  anterior  end  of  the  primitive  gut,  which  lies 
beneath  that  region  of  the  neural  tube  which  afterwards  becomes 
the  mid-brain,  to  the  caudal  end  of  the  embryo  (figs.  571,  572).  The 
notochord  is  subsequently  obliterated  by  the  formation  of  the  verte- 
brae from  the  protovertebral  somites. 


14     7 


FIG.  571. — Diagram  of  a  transverse  section 
through  a  mammalian  embryo  at  the 
period  when  the  folding  off  of  the  fetus 
has  commenced.  1,  Neural  tube ;  2, 
protovertebral  somite ;  3,  epiblast ;  4, 
somatic  mesoblast ;  5,  splanchnic  meso- 
blast ;  6,  hypoblast ;  7,  notochord ;  8, 
primitive  alimentary  canal ;  9,  coelom ; 
10,  vitello-intestinal  duct ;  11,  yolk-sac  ; 
12,  lateral  fold  of  amnion. 


FIG.  572.— Diagram  of  a  longitudinal  section  of  a 
mammalian  embryo  at  the  period  when  the  folding 
off  of  the  foetus  has  commenced.  1,  Neural  tube  ; 
2,  epiblast ;  3,  notochord  ;  4,  stomadoeai  space  ;  5, 
head  fold  of  amnion  ;  6,  tail  fold  of  amnion  ;  7, 
hypoblast ;  8,  somatic  mesoblast ;  9,  splanchnic 
mesoblast ;  10,  yolk-sac  ;  11,  coelom  ;  12,  allantois  ; 
13,  hind-gut ;  14,  mid-gut ;  15,  fore-gut;  16,  peri- 
cardium. 


The  foetus  contains  parts  of  all  the  layers  of  the  blastoderm,  and 
from  each  of  these  certain  organs  are  formed  as  indicated  in  the 
following  list: — 

1.  From  Epiblast. — a.  The  epidermis  and  its  appendages. 
&.  The  nervous  system,  both  central  and  peripheral. 

c.  The  epithelial  structures  of  the  sense-organs. 

d.  The  epithelium  of  the  mouth,  and  the  enamel  of  the  teeth. 

e.  The  epithelium  of  the  nasal  passages. 

/.  The  epithelium  of  the  glands  opening  on  the  skin  and  into  the 
vestibule  of  the  mouth,  and  nasal  passages. 
g.  The  muscular  fibres  of  the  sweat-glands. 

2.  Prom  Mesoblast. — a.  The   skeleton   and    all    the   connective 
tissues  of  the  body. 

b.  All  the  muscles  of  the  body  (except  those  of  the  sweat-glands). 

c.  The  vascular  system,  including  the  lymphatics,  serous  mem- 
branes, and  spleen. 


CH.  LIX.] 


THE   DECIDUA    OF   FCETAL   MEMBRANES 


887 


d.  The  urinary  and  generative  organs,  except  the  epithelium  of 
the  bladder  and  urethra. 

The  Somatic  mesoblast  forms  the  osseous,  fibrous,  and  muscular 
tissues  of  the  body-wall,  including  the  true  skin. 

The  Splanchnic  mesoblast  forms  the  fibrous  and  muscular  wall  of 
the  alimentary  canal,  the  vascular  system,  and  the  urine-genital 
organs. 

3.  Prom  Hypolblast. — a.  The  epithelium  of  the  alimentary  canal 
from  the  inner  sides  of  the  teeth  to  the  anus,  and  that  of  all  the 
glands  (including  liver  and  pancreas)  which  open  into  this  part  of 
the  alimentary  tube. 

b.  The  epithelium  of  the  respiratory  cavity. 

c.  The  epithelium  of  the  Eustachian  tube  and  tympanum. 

d.  The  epithelium  lining  the  vesicles  of  the  thyroid. 

e.  The  epithelial  nests  of  the  thymus. 

/.  The  epithelium  of  the  bladder  and  urethra. 


THE  DECIDUA  AND  THE  FCETAL  MEMBRANES 

When  the  uterus  is  ready  for  the  reception  of  an  embryo  it  is  lined 
by  a  greatly  hyper trophied  mucous  membrane;  this  is  called  the 
decidua,  because,  after  the  delivery  of  the  child,  a  portion  of  it  comes 
away  from  the  uterus  with  the  other  membranes. 

The  ovum  has  been  fertilised 
in  the  Fallopian  tube,  and  the 
embryo,  by  the  time  it  reaches 
the  uterine  cavity,  has  usually 
reached  the  stage  of  a  morula  or 
blastula.  It  rapidly  eats  its  way 
into  the  substance  of  the  decidua 
which  closes  over  it,  obliterating 
opening  through  which  it 
and  thus  the  embryo 
becomes  imbedded  in  the  mem- 
brane, which  thereupon  becomes 
separable  into  three  parts.  1.  The 
part  between  the  embryo  and  the 
muscular  wall  of  the  uterus,  the 
decidua  basalis  or  serotina.  2.  The 
part  between  the  embryo  and  the 
uterine  cavity,  the  decidua  capsu- 
laris  or  reflexa.  3.  The  remaining 
part  is  called  the  decidua  vera. 
Between  the  decidua  capsularis  and  the  decidua  basalis  lies  the 
embryo,  which  speedily  becomes  differentiated  into  the  foetus  and 


the 


FIG.  573. — Diagram  representing  the  relation  of 
the  developing  embryo  to  the  decidua  at  a  very 
early  stage.  1,  Uterine  muscle ;  2,  epi  blast 
of  embryo ;  8,  inner  cell  mass  of  embryo ; 
4,  decidua  basalis  ;  5,  decidua  capsularis  ; 
6,  decidua  vera  ;  7,  cavity  of  uterus. 


888         REPRODUCTION,    DEVELOPMENT,   GROWTH   AND   DEATH       [CH.  LIX. 


its  membranes.  The  outermost  of  the  foetal  membranes  is  the  chorion ; 
this  is  covered  with  vascular  villi,  which  dip  into  the  decidua  capsu- 
laris  and  basalis.  Inside  the  chorion  is  the  amnion,  a  closed  sac,  which 
surrounds  the  embryo  and  is  attached  to  its  ventral  wall  at  the 
umbilicus.  The  amnion  is  filled  with  fluid,  the  amniotic  fluid  in 
which  the  foetus  floats,  and  it  forms  a  sheath  for  the  umbilical  cord  by 
which  after  a  certain  time,  the  foetus  is  attached  to  the  inner  surface 
of  the  chorion,  or  outer  embryonic  membrane.  The  umbilical  cord 

contains  not  only  the  blood- 
vessels which  pass  between 
a  specialised  portion  of  the 
chorion,  which  forms  the 
foetal  part  of  the  placenta, 
and  the  foetus,  but  also 
the  remains  of  the  yolk-sac, 
and  the  duct  by  which  it  is 
connected  with  the  intestine 
of  the  foetus.  In  animals 
which  develop  outside  the 
mother's  body  (for  instance, 
birds)  the  yolk-sac  is  much 
larger  and  is  the  great 
source  of  nutriment  during 
growth. 

As  the  embryo  grows, 
the  decidua  capsularis  is  ex- 
panded over  its  surface,  and 
as  the  growth  continues  the 
uterine  cavity  is  gradually  obliterated,  and  the  decidua  capsularis  is 
forced  into  contact  with  the  decidua  vera,  with  which  it  fuses. 

As  the  decidua  is  merely  thickened  mucous  membrane,  it  naturally 
contains  glands  which  become  enlarged  as  the  decidua  thickens.  It 
was  believed,  at  one  time,  that  the  villi  of  the  chorion  entered  the 
glands,  but  this  is  now  known  to  be  incorrect.  The  villi  enter  the 
interglandular  substance,  and,  in  the  human  subject,  the  glands  of  the 
decidua  capsularis  eventually  disappear  entirely.  In  the  decidua 
basalis  and  the  decidua  vera  the  superficial  portions  of  the  glands 
also  disappear;  their  deep  portions  remain  in  an  almost  unchanged 
condition,  and  furnish  the  epithelium  for  -the  regeneration  of  the 
glands  and  the  lining  of  the  uterine  cavity  after  parturition.  The 
intermediate  parts  of  the  glands  in  the  decidua  vera  and  the  decidua 
basalis  become  very  much  enlarged,  and  form  a  stratum  of  the 
decidua  called  the  spongy  layer,  and  ultimately  this  layer  is  converted 
into  a  series  of  clefts,  and  it  is  along  the  line  of  these  clefts  that  the 
decidua  is  separated  at  birth, 


FIG.  574. — Diagram  representing  a  later  stage  of  develop- 
ment than  that  shown  in  fig.  573.  1,  Uterine  muscle  ; 
2,  villi  of  chorion  of  embryo ;  3,  coalom ;  4,  decidua 
basalis  ;  5,  decidua  capsularis ;  6,  decidua  vera ;  7,  cavity 
of  uterus  ;  8,  allantois  ;  9,  amnion  cavity  ;  10,  primitive 
intestine ;  11,  yolk-sac. 


CH.  LIX.] 


THE  PLACENTA 


889 


In  some  mammals  in  which  the  connection  between  the  chorion 
and  the  decidua  is  less  intimate  than  in  the  human  subject,  the 
glands  persist  to  a  greater  or  less  extent,  and  secrete  a  fluid  called 
uterine  milk,  which  is  absorbed  by  the  chorion. 

The  portion  of  the  decidua  which  undergoes  the  greatest  change  is 
the  decidua  basalis.  In  it  a  number  of  large  blood  spaces  are  formed, 
and  these  are  separated  into  masses  or  cotyledons  by  fibrous  strands. 


Fio.  575.— Diagrammatic  view  of  a  vertical  transverse  section  of  the  uterus  at  the  seventh  or  eighth 
week  of  pregnancy,  c,  c,  c7,  Cavity  of  uterus,  which  becomes  the  cavity  of  the  decidua,  opening  at 
c,  c,  the  cornua,  into  the  Fallopian  tubes,  and  at  cf  into  the  cavity  of  the  cervix,  which  is  closed  by 
a  plug  of  mucus ;  dv,  decidua  vera ;  dr,  decidua  reflexa,  with  the  sparser  villi  imbedded  in  its 
substance;  ds,  decidua  basalis  or  serotina,  involving  the  more  developed  chorionic  villi  of  the 
commencing  placenta.  The  foetus  is  seen  lying  in  the  amniotic  sac ;  passing  up  from  the  umbilicus 
is  seen  the  umbilical  cord  and  its  vessels  passing  to  their  distribution  in  the  villi  of  the  chorion  ; 
also  the  pedicle  of  the  yolk-sac,  which  lies  in  the  cavity  between  the  amnion  and  chorion.  (Allen 
Thomson.) 

The  cotyledons  are  penetrated  by  chorionic  villi,  and  it  is  this  con- 
junction of  chorionic  villi  and  decidua  basalis  which  produces  the 
placenta.  The  blood-vessels  of  the  chorionic  villi  are  formed  by  the 
mesoblastic  covering  of  the  allantois,  another  foetal  outgrowth.  Its 
origin  from  the  hind -gut  is  shown  in  fig.  5*72. 

The  placenta  is  the  organ  of  foetal  nutrition  and  excretion,  and  at 
full  term  it  is  seven  or  eight  inches  across  and  weighs  nearly  a  pound. 
Its  blood  sinuses  are  filled  with  maternal  blood,  which  is  carried  to 


890         REPRODUCTION,   DEVELOPMENT,    GROWTH   AND   DEATH       [CH.  LIX. 


them  by  the  uterine  arteries  and  away  from  them  by  the  uterine  veins. 

Into  these  blood-filled  spaces  the  vascular  foetal  villi  project  ;  hence 

it  is  easy  for  exchanges  to 
take  place  between  the 
foetal  and  the  maternal 
blood,  though  the  two 
blood-streams  never  mix  to- 
gether. Oxygen  and  nutri- 
ment pass  from  the  maternal 
blood  through  the  coverings 
of  the  f  cetal  vessels  into  the 
fcetal  blood,  and  carbonic 
acid,  urea,  and  other  waste 
products  pass  in  the  con- 
trary direction.  The  fcetal 
blood  is  carried  to  the 
placenta  by  the  umbilical 
arteries,  which  are  the  ter- 
minal branches  of  the  aorta 

°*  ^ne  ICetiUS  ;    these  paSS  to 

ment  of  membranes  and  placenta  than  that  shown  in      the  T)lacenta  bv  the  Umbili- 
fig.  574.    1,  Uterine  muscle  ;  2,  placenta  ;  3,  yolk-sac  ;  ,    *        -,  J  . 

4,  fused  decidua  vera  and  capsularis  ;  5,  primitive  blood-      Cal    COrd,    and    the    blOOQ    IS 

i     ,1  -i     ,1  i 

returned,  through  the   COrd, 

ty  ftiQ  umbilical  Vein. 

The  amniotic  fluid  consists  of  water  containing  small  quantities 
of  protein,  urea,  and  salts.  It  is  an  exudation  from  the  fcetal  and 
the  maternal  blood,  and  the  urea  in  it  comes  from  the  fcetal  urine 
which  is  poured  into  the  amniotic  cavity  in  the  later  part  of 
pregnancy.  Its  function  is  mainly  mechanical;  it  supports  the 
embryo  on  all  sides,  and  protects  it  from  blows  and  other  injuries  to 
the  abdomen  of  the  mother,  and  from  sudden  irregular  contractions 
of  the  abdominal  walls. 

Intra-vitam  Staining.  —  Within  the  last  few  years  Goldmann  of 
Freiburg  has  made  observations  in  which  he  has  injected  animals 
(rats  and  mice)  with  certain  blue  solutions  of  which  pyrrhol-blue  may 
be  taken  as  an  example.  The  animal  suffers  from  no  ill  effects,  the 
only  outward  change  being  that  a  white  rat  becomes  a  blue  rat. 
When  the  animal  is  subsequently  killed,  the  stain  is  found  embodied 
in  the  granules  of  specific  cells  throughout  the  body.  Although  it 
circulates  in  the  blood,  no  blood  corpuscle  takes  it  up,  nor  has  it  any 
effect  on  the  vascular  lining.  In  the  skin  it  is  found  in  the  fixed 
connective  tissue  cells,  but  chiefly  in  free  phagocytic  cells  in  the 
lower  layers  of  the  cutis  and  subcutis.  But  these  migratory  cells 
appear  also  in  every  internal  organ  (except  the  nervous  system), 
and  always  in  connection  with  interstitial  fibrous  tissue;  they 


FIG.  576.—  Diagram  representing  a  later  stage  of  develop- 


vessel  of  embryo;  6,  amnion  cavity  (outer  surface  of 
amnion  is  fused  with  inner  surface  of  chorion)  ;  7,  urn- 
bilical  cord  ;  8,  foetal  villas  in  placenta. 


CH.  LIX.]  THE   FOZTAL  CIRCULATION  891 

occur  in  muscles,  glands,  tendons,  and  especially  in  serous  membranes. 
On  account  of  their  affinity  for  pyrrhol-blue  they  were  originally 
termed  pyrrhol  cells,  and  it  seems  probable  that  they  originate  in 
the  bone  marrow. 

By  means  of  such  intra-vitam  stains  one  can  further  differentiate 
the  Kupffer-cell  of  the  liver,  the  reticulum  cell  of  lymph  glands  and 
spleen,  the  interstitial  cell  of  the  testis,  the  follicular  cell  in  the 
maturing  follicles  of  the  ovary,  the  cortical  cell  of  the  suprarenal, 
the  epithelial  covering  of  the  choroid  plexuses,  and  the  cells  which 
line  the  convoluted  tubules  of  the  kidney. 

When  pregnancy  occurs  in  the  stained  animal,  the  appearance 
and  behaviour  of  the  placenta  are  most  striking;  the  blue  colour 
disappears  from  the  skin  and  is  concentrated  in  the  uterus,  and 
in  time  the  latter,  forming  a  centre  of  attraction  for  the  dye, 
ultimately  dispossesses  all  the  remaining  tissues  of  their  blue.  In 
the  uterus  it  is  the  free  cells  of  the  decidua  basalis  where  the  stain 
is  mainly  found.  In  quite  early  stages  the  stained  cells  penetrate 
into  the  primitive  placenta  and  cast  off  their  stained  granules, 
which  are  snatched  up  by  foetal  cells  in  the  way  nutritive  material 
is.  But  when  once  the  placenta  has  attained  maturity,  the  dye 
is  found  only  in  the  foetal  cells  which  form  the  layer  which  separates 
the  maternal  and  foetal  tissues.  The  foetus  itself  remains  per- 
fectly colourless,  the  stain  not  being  able  to  penetrate  this  protective 
barrier.  Further  research  has  shown  another  important  point, 
for  the  same  cells  which  vigorously  absorb  the  vital  stain  store  also 
glycogen,  fat,  and  haemoglobin  temporarily  before  these  substances 
pass  into  the  foetal  circulation.  The  avidity  of  such  cells  for  the 
dye  is  thus  connected  with  their  functional  activity  in  relation  to 
really  nutritive  material;  the  importance  of  vital  staining  in 
embryological  research  is  therefore  apparent. 

Equally  important  are  its  applications  to  pathological  research, 
but  into  this  aspect  of  the  question  it  will  be  beyond  our  purpose 
to  pass. 

THE  FCETAL  CIRCULATION 

We  shall  not  enter  into  the  complex  manner  in  which  the  heart 
and  blood-vessels  of  the  foetus  develop  from  the  embryonic  rudiments ; 
but  when  these  are  fully  formed  the  circulation  of  the  blood  is  found 
to  differ  considerably  from  that  which  occurs  after  birth.  It  will 
be  convenient  to  begin  its  description  by  tracing  the  course  of  the 
blood,  which,  after  being  carried  to  the  placenta  by  the  two  umbilical 
arteries,  has  returned,  oxygenated  and  replenished,  to  the  foetus  by 
the  umbilical  vein. 

It  is  at  first  conveyed  to  the  under  surface  of  the  liver,  and  there 
the  stream  is  divided, — a  part  of  the  blood  passing  straight  on  to  the 


892         REPRODUCTION,   DEVELOPMENT,   GROWTH  AND   DEATH       fCH.  LIX. 

inferior  vena  cava,  through  a  venous  canal  called  the  ductus  venosus, 
while  the  remainder  passes  into  the  portal  vein,  and  reaches  the 
inferior  vena  cava  after  circulating  through  the  liver.  Whether, 
however,  by  the  direct  route  through  the  ductus  venosus  or  by  the 
roundabout  way  through  the  liver, — all  the  blood  which  is  returned 


PIG.  577.— Diagram  of  the  Foetal  Circulation. 

from  the  placenta  by  the  umbilical  vein  reaches  the  inferior  vena 
cava  at  last,  and  is  carried  by  it  (together  with  the  blood  from  the 
lower  part  of  the  body  and  lower  limbs)  to  the  right  auricle  of  the 
heart,  into  which  cavity  is  also  pouring  the  blood  that  has  circulated  in 
the  head  and  neck  and  arms,  and  has  been  brought  to  the  auricle  by  the 


CH.  LIX.]  PARTURITION  893 

superior  vena  cava.  It  might  be  naturally  expected  that  the  two 
streams  of  blood  would  be  mingled  in  the  right  auricle,  but  such  is 
not  the  case,  or  only  to  a  slight  extent.  The  blood  from  the  superior 
vena  cava — the  less  pure  fluid  of  the  two — passes  almost  exclusively 
into  the  right  ventricle,  through  the  auriculo-ventricular  opening,  just 
as  it  does  in  the  adult ;  while  the  blood  of  the  inferior  vena  cava  is 
directed  by  the  fold  of  the  lining  membrane  of  the  heart,  called  the 
Eustachian  valve,  through  the  foramen  ovale  into  the  left  auricle, 
whence  it  passes  into  the  left  ventricle,  and  out  of  this  into  the  aorta, 
and  thence  to  all  the  body,  but  chiefly  to  the  head  and  neck.  The 
blood  of  the  superior  vena  cava,  which,  as  before  said,  passes  into  the 
right  ventricle,  is  sent  out  from  there  in  small  amount  through  the 
pulmonary  artery  to  the  lungs,  and  thence  to  the  left  auricle,  by  the 
pulmonary  veins,  as  in  the  adult.  The  greater  part,  however,  does 
not  go  to  the  lungs,  but  instead,  passes  through  a  canal,  the  ductus 
arteriosuA,  leading  from  the  pulmonary  artery  into  the  aorta  just  below 
the  origin  of  the  three  great  vessels  which  supply  the  upper  parts  of 
the  body ;  and  there  meeting  that  part  of  the  blood  of  the  inferior 
vena  cava  which  has  not  gone  into  these  large  vessels,  it  is  distributed 
with  it  to  the  trunk  and  other  parts — a  portion  passing  out  by  way 
of  the  two  umbilical  arteries  to  the  placenta.  From  the  placenta  it 
is  returned  by  the  umbilical  vein  to  the  under  surface  of  the  liver, 
from  which  the  description  started. 

PARTURITION 

During  pregnancy  the  uterus  and  its  contents  increase  in  size, 
and  we  have  already  alluded  to  the  changes  in  its  mucous  membrane 
or  decidua,  and  the  formation  of  the  placenta ;  the  principal  factor 
in  the  distension  of  the  uterus  is  the  accumulation  of  the  amniotic 
fluid.  The  muscular  wall  of  the  uterus  also  hypertrophies ;  this  is 
in  part  due  to  the  formation  of  new  muscular  fibres,  and  in  part  of 
the  increase  in  size  of  the  pre-existing  muscular  fibres.  The 
muscular  wall  is  one  of  immense  strength. 

The  foetus  "  comes  to  term  "  in  the  human  subject  on  the  tenth 
menstrual  epoch  after  conception;  this  averages  about  280  days 
after  the  last  menstruation.  Delivery  is  the  result  of  uterine 
contractions  or  "labour  pains";  the  liquor  amnii  is  thus  forced 
downward  and  presses  the  membrane  formed  by  the  fused  amnion 
and  chorion  through  the  cervix  of  the  uterus  which  is  gradually 
distended.  When  the  distension  is  sufficient  the  membrane  ruptures, 
and  the  amniotic  fluid  escapes.  The  os  is  then  fully  distended,  and 
the  foetal  head  enters  the  pelvis ;  the  pains  become  more  frequent 
and  energetic,  and  the  voluntary  muscles  of  the  abdomen  are  brought 
into  play,  so  that  ultimately  the  new-born  child  is  expelled  to  the 


894    REPRODUCTION,  DEVELOPMENT,  GROWTH  AND  DEATH   [CH.  LIX. 

exterior.  The  process  usually  lasts  some  hours,  bufc  the  time  is  much 
prolonged  (ten,  twenty,  or  even  more  hours)  in  the  birth  of  a  first 
child.  The  child  is  still  connected  with  the  placenta  by  the  umbilical 
cord,  which  is  about  20  inches  long,  and  this  connection  should  not 
be  severed  for  a  few  minutes  in  order  that  as  much  blood  as  possible 
may  be  aspirated  from  the  foetal  part  of  the  placenta  into  the  child 
as  breathing  commences. 

After  the  child  is  expelled,  the  contractions  of  the  uterine  walls 
recommence  after  a  lapse  of  twenty  to  thirty  minutes,  and  the 
placenta  is  separated  and  forced  out.  The  separation  extends 
through  the  decidua  along  the  line  of  the  stratum  spongiosum,  and 
the  fused  chorion,  amnion  and  decidua  turned  inside  out,  follow  the 
placenta  to  which  they  are  attached,  constituting,  with  the  placenta, 
the  after-birth. 

After  the  umbilical  cord  is  tied  and  separated,  the  umbilical 
arteries  inside  the  child  become  filled  with  blood-clot,  and  ultimately 
they  are  converted  into  fibrous  cords,  the  so-called  obliterated  hypo- 
gastric  arteries,  and  at  the  same  time  the  allantois  is  also  converted 
into  a  fibrous  strand,  the  urachus,  which  extends  from  the  apex  of  the 
bladder  to  the  umbilicus. 

The  haemorrhage  from  the  uterus  which  accompanies  and  follows 
the  after-birth  may  be  profuse  at  first,  but  under  normal  circum- 
stances is  soon  checked  by  the  firm  contraction  of  the  uterine 
walls. 

Although  it  has  been  shown  that  delivery  may  occur  when  all  nerves  connect- 
ing the  uterus  with  the  central  nervous  system  are  cut  through  (see  p.  721),  the 
contractions  of  the  organ  are  normally  influenced  reflexly  through  the  nervous 
system.  Stimulation  of  various  sensory  nerves  will  produce  contractions  of  the 
pregnant  uterus,  and  premature  delivery  may  occur  as  the  result  of  mental  and 
physical  disturbances. 

The  determining  factor  which  produces  the  labour  pains  at  a  particular  date 
has  been  much  discussed;  some  suppose  it  may  be  maternal  in  origin,  such  as 
a  degenerative  condition  set  up  in  the  placenta  or  decidua,  whereas  others  consider 
the  initial  impulse  may  come  from  the  foetus,  which  secretes  certain  products  that 
stimulate  uterine  contraction. 

After  delivery,  the  uterus  undergoes  reduction  in  size  at  a  fairly 
rapid  rate.  This  has  been  attributed  to  fatty  degeneration,  but  of 
this  there  is  but  little  evidence.  The  theory  at  present  most  in 
vogue  to  explain  "  involution  of  the  uterus "  is  that  the  process  is 
one  of  autolysis  due  to  the  action  of  intracellular  digestive  enzymes. 
Whilst  it  is  occurring,  the  urine  of  the  mother  contains  a  good  deal 
of  creatine,  a  substance  which  is  normally  absent  from  that  secretion. 
It  has  been  supposed  tha-t  this* 'substance  originates  from  the  rapid 
destruction  of  the- uterine /muscte.  -  It  has,  however,  been  shown  that 
creatine  occurs  aftef '  delivery  even  if  the  uterus  is  amputated,  so 
that  the  muscular  creatine  cannot  then  be  the  source  of  the  urinary 


OIL  LIX.]  DEATH  895 

creatine;  there  is  some  evidence  that  the  creatine  is  associated  in 
some  way  with  the  metabolism  of  the  mammary  gland. 

The  atrophy  or  involution  of  the  uterus  which  occurs  at  the 
menopause  appears  also  to  be  produced  in  the  same  way,  and  it  has 
been  suggested,  with  some  reason,  that  the  symptoms  exhibited  at 
that  period  of  life  may  be  in  part  explained  as  due  to  the  absorption 
of  the  products  of  the  autolysis  of  the  uterine  tissue. 

DEATH 

We  have  now  completed  the  task  we  set  ourselves,  and  having 
arrived  at  the  new-born  child  have  reached  the  point  in  the  life 
cycle  from  which  we  set  out.  The  bearers  and  transmitters  of  the 
germ  plasm,  its  hosts,  the  parents,  pass  away  in  due  course,  making 
room  for  their  successors  who  live,  repeat  the  process,  and  likewise 
die  in  their  turn. 

It  is  not  altogether  inappropriate  to  conclude  a  book  which  deals 
with  life,  by  a  few  sentences  on  Death,  which  forms  the  final  chapter 
for  each  individual.  As  the  prime  of  life  is  past,  signs  of  old  age 
begin  to  appear,  the  eyes  become  feeble,  the  hair  becomes  grey,  the 
cartilages  calcify,  the  muscles  become  weaker,  digestion  gets  feebler, 
and  metabolism  in  every  way  more  and  more  imperfect.  If  this 
continues,  life  is  ultimately  terminated  by  natural  death,  in  which 
the  functions  get  weaker  and  weaker  and  finally  cease.  Death  from 
old  age  is,  however,  comparatively  rare ;  the  common  cause  of  death  is 
accident,  in  which  term  we  include  disease.  In  the  activity  of  youth 
many  a  disease  is  vanquished,  but  as  the  powers  of  resistance 
diminish  with  increasing  years,  some  ailment  usually  upsetting  more 
particularly  some  important  organ  will  ultimately  find  the  body 
unable  to  repel  its  attack. 

"  That  ends  this  strange,  eventful  history." 

COMPLIMENTS 


OF 


F.  Boston's  Son  Co, 


,  Pi 


INDEX 


A. 


Abderhalden's  feeding  experiments,  545 
Abdominal  muscles,  action  in  respiration,  357 
Abdominal  reflex,  711 
Abducens  nerve,  663,  674 

centre,  674 
Aberration, 

chromatic,  830 

spherical,  ib. 
Abiuretic  products,  519 
Abrin,  475 
Absorption 

of  carbohydrates,  544 
fats,  546,  547 
food,  543  et  seq. 
proteins,  544 

by  the  skin,  608 
Acapnia,  402 
Accelerator  nerves,  144 

uriuae,  580 

Accessoiy  auditory  nucleus,  676 
Accommodation  of  eye,  820,  824  et  scq. 

defects  of,  828, 831 

mechanism  of,  825 
Acetonaemia,  542 
Acetyl,  416 

Achromatic  spindle,  16,  876 
Achromatin,  10 
Achromatopsia,  848 
Achroo-dextrin,  412,  505 
Acida'inia,  542,  619 
Acids  in  gastric  juice,  511 
Acid-albumin,  433 
Acidosis,  542,  619 
Acini  of  secreting  glands,  496,  498 
Acoustic  tubercle,  676 
Acrolein,  415 
Acromegaly,  343 
Acrylic  series,  414 
Adamantoblasts,  58,  59 
Adamkiewicz  reaction,  425,  429 
Adam's  apple,  800 
Adaptation  in  sensations,  774 
Addison's  disease,  341,  342 
Adenase,  594 
Adenine,  432,  593 
Adenoid  or  lymphoid  tissue,  35 
Adipose  tissue,  28,  33-35.    See  Fat, 

cells,  34,  35 

development,  33 

situations  of,  ib. 

structure,  ib. 

uses,  84 

vessels  and  nerves,  34,  35 
Adrenaline,  342 

administration  of,  541 

effect  of,  on  salivary  gland,  503 


ALIMENTARY  CANAL. 

Adsorption,  328  n. 

Aerobic,  438 

Aerotonometer,  363 

/Esthesiometers,  772 

Affective  mode  in  consciousness,  758 

tone,  763 
Afienspalte,  736 

Afferent  fibres  when  entering  the  spinal  cord,  703 
Afferent  nerves,  73,  144  et  seq. 

projection  system,  700 

root-cells,  194 
After-birth,  894 
After-images,  844 
After-sensations,  764 
Agglutinin,  470 
Agraphia,  809 
Air, 

atmospheric,  composition  of,  392 

breathing,  358 

changes  by  breathing,  392 

complemental,  359 

quantity  breathed,  ib. 

reserve,  ib. 

residual,  ib. 

tidal,  ib. 

transmission  of  sonorous  vibrations  through. 
794 

undulations  of,  conducted  by  external  ear,  795 
Air-calorimeters,  631,  633 
Air-sacs,  351,  352 
Air -tubes.    See  Bronchi. 
Airy's  discovery  of  astigmatism,  829 
Alanine,  417,  422 
Albumin,  424,  427,  483,  601 

absence  of  glycine  from.  422 

acid,  433 

alkali,  433 

character  of,  515 

egg,  433 

of  blood,  454 
Albuminates,  433 
Albuminoids,  428,  429 
Albuminometer,  Esbach's,  601 
Albuminous  alveoli,  499 
Albuminous  substances.    See  Proteins. 

action  of  gastric  fluid  on,  519 
Albumins,  424,  427 
Alcapton,  602 
Alcaptonuria,  602 

Alcohol  as  an  accessory  to  food,  490 
Alcohols,  monatomic,  408 
Aldehyde,  407 
Aldoses,  407 
Alimentary  canal,  492  ct  scq. 

glycosuria,  538 

nerves  of,  568 


3  L 


898 


INDEX 


ALKALI-ALBUMIN. 

Alkali-albumin,  433 

properties  of,  ib. 
Allantoin,  592 

Allantois,  development  of,  886 
Allochiria,  777 
Alloxan,  592 
Allyl  alcohol,  415 
Alveolar  air  apparatus,  373-375 
Alveoli,  498-500 
Amacrine  cells,  816 
Amino-acids,  416,  433,  545,  603 
Amino-caproic  acid,  417 
AminQ-oxypyrimidine,  421 
Ammonia,  421,  588,  589 

cyanate  of,  isomeric  with  urea,  583 
Amnion,  886,  888,  890 
Amniotic  cavity,  888 

fluid,  888,  890 
Amoeba,  5, 11,  867 
Amoeboid  movements,  11  et  seq.,  86 

cells,  5,  13 

colourless  corpuscles,  14,  455 

cornea-cells,  813 

protoplasm,  11 

Tradescantia,  12,  13 
Amyloids  or  starches,  412 

action  of  pancreas  and  intestinal  glands,  519 

of  saliva  on,  613 
Amylolytic  enzymes,  440 
Amylopsin,  action  of,  519 
Anabolic  nerve  groups,  203 
Anabolic  phenomena,  612 
Anacrotic  pulse,  293 
Anaerobic,  438 
Anaphylaxis,  478 

Anderson  on  the  auto-genetic  theory,  150,  151 
Anelectrotonus,  171, 173 
Angina  pectoris,  312 
Angio-neuroses,  311 
Angular  convolution,  693 
Angulus  opticus  seu  visorius,  823 
Animal  cell,  structure  of,  7  et  seq. 
Animal  heat.    See  Heat  and  Temperature. 
Anions,  322 
Ankle-clonus,  712 
Ajinulus  of  Vieussens,  196,  251,  302 
Anosmatic  animals,  786 
Antagonistic  muscles, 

reciprocal  action  of,  714 
Antero-lateral  ascending  tract,  658 
Antero-lateral  descending  tract,  656 
Antidromic,  803 
Anti-enzymes,  443 
Antilytic  secretion,  503 
Antithrombin,  448,  450,  451 
Antitoxin,  474,  475 
Anvil  bone,  789 
Aphasia,  733,  809 
Apnrea,  origin  of,  379 
Apoplexy,  689 

Aqueduct  of  Sylvius,  644,  645,  663,  671 
Aqueductus  FallopiS,  790 
Aqueous  humour,  811 
Arbor  vitse,  681 
Archenteron,  884  et  seq. 
Archipallium,  646, 647,  698 
Arcuate  fibres,  668 
Area  cheiro-kinsesthetic,  741 

germinal,  or  embryonic,  883 

glosso-kinsesthetic,  741 
Areas,  of  Cohnheim,  65 

intermediate,  742,  743 

primary,  ib. 

terminal,  ib. 
Areolse,  29,  48,  49 
Areolar  tissue,  28  et  seq. 


AUTONOMIC  NERVOUS  SYSTEM 

Arginase,  587 

Arginine,  420,  422 

Argyll- Robertson  pupil,  834 

Arteria  centralis  retinae,  815,  820 

Arteries  recta;,  570 

Arterial  blood-pressure,  277,  280 

venous  blood,  difference  between,  371 
Arterial  tension  in  asphyxia,  391 
Arteries,  216  et  seq. 

bronchial,  353 

circulation  in,  velocity  of,  281 

coronary,  237 

development  of,  891 

distribution,  216 

elasticity,  265 

interlobular,  569 

muscularity,  266 

nerves  of,  218 

nervous  system,  influence  of,  311 

pressure  of  blood  in  asphyxia,  391 

pulse,  290  et  seq. 

renal,  ligature  of,  580 

rhythmic  contraction,  266 

structure,  217  et  seq. 

umbilical,  894 

velocity  of  blood-flow  in,  281 
Arterioles,  264,  278 
Articulate  sounds,  classification  of,  808 

vowels  and  consonants,  ib. 
Articulation  positions,  808 
Artifacts,  8 

Artificial  respiration,  383,  387 
Aryteno-epiglottidean  fold,  805 
Arytenoid  cartilages,  797,  805 

effect  of  approximation,  800 

movements  of,  ib. 
Arytenoid  muscle,  799,  801,  802 
Ascaris,  ovum  of,  11,  17 
Ascending  tubule  of  Henle,  567 
Aspergillus  niger,  545 
Asphyxia,  305,  389  et  seq. 

causes  of  death  in,  390 

conditions    of   the    vascular    system    in,  389, 
390 

symptoms,  389 

tracings  of,  391 
Assimilation,  power  of,  6 
Association  centres,  740,  741 

fibres,  698,  740 

tracts,  704 
Astigmatism,  829 
Atmospheric  air.    See  Air. 

composition  of,  392 

pressure  in  relation  to  respiration,  385 
Atropine,  effect  of, 

on  heart,  253 

on  salivary  gland,  503 
Attraction  sphere,  7, 10, 16 
Atwater-Benedict  calorimeter,  633 
Auditory  area,  738 
Auditory  nerve,  663,  676 

diagrams  of,  676,  677 

origin,  676 

word  centre,  809 
Auerbach's  plexus,  79,  554,  563 
Auricles  of  heart.    See  Heart. 
Auricular  diastole,  232,  233 
Auricular  systole,  ib. 
Auriculo-ventricular  bundle,  213,  257 

valves.    See  Heart  valves. 
Autogenetic  nerve  theory,  150 
Auto-intoxication  theory  of  the  ductless  glands, 

332 

Autolysis,  136,  440 
Autolytic  enzymes,  440 
Autonomic  nervous  system,  196  et  seq. 


INDEX 


899 


AVOGADRO'S  LAW. 

Avpgadro's  law,  320,  392 
Axipetal  conduction,  law  of,  191 
Axis-cylinder  of  nerve-fibre,  74,  185 
Axons.    See  Nerves. 


B. 


Babinski's  sign,  714 

Bacilli,  types  of,  438 

Bacterial  action  in  intestinal  digestion,  525 

Bacterio-lysin,  473,  475 

Bacterium  lactis,  414 

Barcroft's  tonometer,  366 

Barnard's  cardiometer,  248 

Basal  ganglia,  687,  726 

Basilar  membrane  of  ear,  792,  793 

Basophile  cells,  457 

Batteries  and  keys,  87  et  seq. 

Daniell  cell,  87,  88 
Bausteine,  545,  627 
Bayliss,  mammalian  heart,  245 

observations  on  vaso-dilator  nerves  of  dogs, 
303 

on  adsorption,  328  n. 

on  pancreatic  secretion,  520 
Bechterew,  nucleus  of,  677 
Beckmann's  differential  thermometer,  326 
Beef- tea,  the  making  of,  489 
Beer's   experiments   on  accommodation    of   the 

eye,  827 

Bellini's  ducts,  567,  568 
Bell's  experiments  on  spinal  nerve  roots,  156 
Bence-Jones'  protein,  601 
Beri-beri,491 
Bernard's  discovery  in  the  liver,  331,  536-539 

experiment  on   independent    muscular    irrita- 
bility, 83 

on  pancreatic  secretion,  523 
Bert's  experiments  on  crossing  of  nerves,  161 
Bethe's  autogenetic  theory,  150 
Betz  cells,  697 
Bezold's  ganglion,  255 
Bicuspid  valve,  213 
Bidder's  ganglion,  255 
Biedermann's  fluid,  83  n. 
Bllaminar  blastoderm,  883 
Bile,  525,  527,  631  et  seq.,  602 

absorption  by  lymph,  536 

analyses  of  human,  532 

canaliculi,  530 

capillaries,  ib. 

characters  of,  531 

constituents  of,  532 

digestive  properties,  525 

doubtful  antiseptic  power,  533 

expelling  mechanism,  535 

human,  analyses  of,  532 

influence  of,  on  fat  absorption,  548 

mixture  with  chyme,  534 

mucin,  532 

pigments,  533 

process  of  secretion,  531 

quantity  secreted,  ib. 

salts,  532 

secretion  and  flow,  531 ,  532 

specific  gravity,  532 

uses,  533- 

Bilirubin,  465,  533 
Biliverdin,  533 
Bimolecular  reactions,  329 
Binocular  colour-mixture,  846 
Binocular  vision,  856,  857 
Biot's  respiration,  405 
Bipolar  nerve-cells,  155, 182  et  seq.,  786 


BLOOD-CORPUSCLES,  RED. 

Birth,  changes  after,  894 

Biuret  reaction,  425 

"Black- water  fever,"  603 

Bladder,  epithelium  of,  22 

Bladder,  urinary.    See  Urinary  bladder. 

Blastocyst,  blastoderm,  blastula,  bilaminar,  883 

et  seq. 

Blastosphere,  881 
"  Blaze  current,"  849 
Blind  spot,  834,  849 
Blocking,  257 
Blood,  28,  29,  60,  61,  444  et  seq. 

agglutinating  action  of,  476 

amino-acids  in,  545 

arterial  and  venous,  difference  between,  215, 
371 

bactericidal  power  of,  473 

buffy  coat,  447 

carbonic  acid  in,  371,  375 

circulation  of,  227  et  seq. 
in  the  foetus,  891 
local  peculiarities,  312 
schema  of,  229 

coagulation,  61 ,  137,  446  et  seq. 

colour,  61,  444 

colouring  matter,  444 
relation  to  that  of  bile,  465 

corpuscles  or  cells  of,  6,  7,  60,  444.    See  Blood- 

corpuscles, 
red,  454 
white  or  colourless,  456 

crystals,  462  et  seq. 

extractive  matters,  454 

fatty  matters,  454 

fibrin,  61, 137,  447 
separation  of,  448 

flow,  velocity  of,  281 

gases  of,  361  et  seq.,  396  et  seq. 

globulicidal  power  of,  473 

haemoglobin.    See  Haemoglobin. 

lymph,  relation  to,  821 

nitrogen  in,  362,  363,  371 

odour  or  halitus  of,  444 

oxalated,  450 

oxygen  in,  362,  365,  372 

oxy haemoglobin.    See  Oxyhajmoglobin. 
photographic  spectrum  of,  462,  463 

plasma,  371,  444,  452 

proteins  of,  452 

quantity,  444 

Haldane's  and  Lorraln  Smith's  experiments, 
445 

reaction,  444,  455 

salts,  454 

serum  of,  446,  452 

specific  gravity,  444 

splenic,  334,  835 

structural  composition,  454 

taste,  444 

temperature,  ib. 

tests  for,  472 

transfusion  of,  319 

in  the  urine,  603 

venous,  61 
Blood-corpuscles,  red,  61,  297,  454 

action  of  reagents  on,  455  et  seq 

chemistry  of,  461 

composition  of,  461 

development  of,  459  et  srq. 

disintegration  and  removal,  334 

emigration  of,  298 

formation  in  the  spleen,  460 

methods  of  counting,  458 

origin  of,  459 

rouleaux,  454 

specific  gravity,  457 


900 


INDEX 


BLOOD-CORPUSCLES,  RED. 

Blood-corpuscles,  red— continued 

stroma,  454 

tendency  to  adhere,  ib. 

vertebrate,  various,  ib. 

Blood-corpuscles,  white,  11,  61,  298,  299,  315,  449, 
456 

amoeboid  movements  of,  457 

chemistry  of,  461 

composition  of,  456 

formation  in  spleen,  334 

origin  of,  461 

varieties,  456 
Blood-crystals,  462  et  seq. 
Blood-flow,  velocity  of,  281 
Blood-gas  analysis,  apparatus  for.  364 
Blood-platelets,  444,  448,  458 
Blood -pressure,  266  et  seq. 

arterial,  277,  280 

in  capillaries,  276 

in  veins,  275 

action  of  respiratory  movements  on,  300 
influence  of  cardiac  nerves  on,  281 

measurement  in  man,  277 

schema  to  illustrate,  267  et  seq. 
Blood-vessels, 

circulation  in,  263  et  seq. 
effect  of  gravity,  279 
time  of  complete,  289 

elasticity  of,  265 

of  eyeball,  820 

nutrient,  42 

of  kidney,  569 

of  muscle,  71 

of  stomach,  509 

influence  of  nervous  system  on,  300 
Body-cavity,  884 
Body,  growth  and  maintenance  of,  626 

synthesis  in  the,  ib. 

Body,  the  chemical  composition  of,  406  et  seq. 
Bohr  on  mountain  sickness,  400 
Boiler-makers'  disease,  798 
Bomb  calorimeter,  631 
Bone,  40  et  seq. 

canalicull,  42 

cancellous,  40 

cells  or  corpuscles,  43 

chemical  composition,  40 

compact,  40 
lamellae  of,  44 

development,  45  et  seq. 

growth,  50 

Haversian  canals,  42 

lacunae,  42,  43 

marrow,  41 

medullary  canal,  41 

microscopic  structure,  42 

ossification  in  cartilage,  46  et  seq. 

ossification  in  membrane,  45 

periosteum  and  nutrient  blood-vessels,  42 

structure,  40  et  seq. 
Bowman, 

on  muscle,  65 
Bowman's  capsule,  566,  567,  576,  579 

glands,  784 

lamina,  812 

renal  epithelium,  576,  577 
Boyle-Mariotte's  law  for  gases,  325 
Brain.  See  Bulb,  Cerebellum,  Cerebrum,  Pons,  etc. 

capillaries  of,  312 

child's,  691,  730,  739 

chimpanzee's,  731 

circulation  of  blood  in,  312  et  seq. 

convolutions,  690  et  seq. 

diagrams  of,  642,  643,  645,  646,  665  et  seq. 

dog's,  729 

extirpation  of,  in  mammals,  723 


CALLEJA,  ISLANDS  OF. 
Brain — continued 


in  foetus,  645,  691 

grey  matter,  181 

lobes,  691  et  seq. 

lunatic's,  751 

monkey's,  691 

motor  areas,  731,  733 

orang's,  691,  731 

primitive,  645 

quantity  of  blood  in,  312,  313 

sensori-motor  area,  734 

sensory  areas,  733 

structure,  643 

ventricles,  644 

vertebrate  (section),  643 

vesicles,  645 

white  matter,  181 
Bread  as  food,  489 
Breathing.    See  Respiration. 
Bright's  disease,  600,  603 
Broca's  convolution,  733,  734,  809 
Brodie,  on  splenic  nerve,  133 

curves  of  extensibility,  110 

his  bellows-recorder,  134,  311 

on  heat  rigor,  139 

rate  of  blood-flow  through  an  organ,  396 
Bronchi,  arrangement  and  structure  of,  347 
Bronchial  arteries  and  veins,  353 
Brown's  staminal  hairs  of  Tradescantia,  13 
Brown-Sequard,  suprarenal  capsules,  341 

on  testis,  878 
Brownian  movement,  81 
Bruch,  membrane  of,  811,  812 
Briicke  on  the  self-steering  action  of  the  heart, 

238 

Brunner's  glands,  494,  509 
Brunton,    after    Gaskell,  tracing   of  actions  of 

vagus  on  the  heart,  250 
Buchanan,  heart  beats,  244 
Buffy  coat,  formation  of,  447 
Bulb,  pons  and  mid-brain,  661  et  seq. 

anterior  aspect,  661 

diagrams  of,  662,  665  et  seq. 

internal  structure,  663  et  seq. 

posterior  aspect,  661 
Bundle  of  Helweg,  656,  657 

of  His,  213,  257 

of  Monakow,  657,  683,  685 
Burch's  experiments  on  colour  vision,  844 
Burdach's  column,  651,  657,  658,  662 
Btitschli  on  spongioplasm,  7 
Butyric  acid,  411,  526 


c. 

Cachexia  strumipriva,  338 

Caecum,  the,  560 

Caffeine,  490 

Caisson  disease,  403 

Cajal,  formation  of  nerve  axons,  153 

law  of  axipetal  conduction,  191 
Calamus  scriptorius,  680 
Calcarine  area,  786 
Calcarine  fissure,  694 
Calcification  of  bone,  47 
Calcium  carbonate,  40,  54 

in  urine,  600 

fluoride,  40,  54 

metabolism,  340 

oxalate  in  urine,  599,  600 

phosphate,  40,  54,  600 

rigor,  261 

Calcium  salts,  the  action  of,  449 
Calleja,  islands  of,  675 


INDEX 


901 


CALLOSAL  CONVOLUTION. 

Callosal  convolution,  694 
Calloso-marginal  fissure,  Hi. 
Calorimeters,  631,  633 
Calyces  of  the  kidneys,  561 

Canal,    alimentary.      See   Stomach,     Intestines, 
etc. 

external  auditory,  753 
function  of,  ib. 

spiral,  of  cochlea,  791 
Canal  of  Schlemm,  813,  814 

of  Petit,  820 
Canaliculi  of  bile,  530 

of  bone,  43 

Canalis  cochlea;,  791,  792 
Canals,  semicircular,  of  ear,  790 
Cancellous  tissue  of  bone,  40 
Cane  sugar,  410 
Cannon,  on  salivary  digestion,  506 

shadow  photographs  of  the  stomach,  showing 

peristaltic  movements,  554 
Capacity  of  chest,  vital,  359 
Capillaries,  61,  214,  222  et  seq. 

bile,  529 

circulation  in,  281,297 
velocity  of,  281 

diameter,  222 

form,  ib. 

influence  on  circulation,  297 

network  of,  222,  223 

number,  223 

passage  of  corpuscles  through  walls  of,  298 

pressure  in,  276  et  seq. 

resistance  to  flow  of  blood  in,  297 

still  layer  in,  ib. 

size,  222 

structure  of,  ib. 
Capillary  flow,  297 
Capsule  of  Bowman,  566,  567 

external  and  internal,  689,  690 

of  Glisson,  528 
Carbamide.    See  Urea. 
Carbohydrates,  406  et  seq. 

absorption  of,  544 

metabolism  of,  614 
Carbonates  in  urine,  596 
Carbonic  acid  in  atmosphere,  375,  376 

in  blood,  371,  375 
effect  of,  373 

increase  in  breathed  air,  392 

influence  of,  on  nerve,  158, 159 

in  lungs,  375 

Carbonic  oxide  haemoglobin,  445,  465,  470 
Carbon  dioxide,  439 

Carbon  monoxide,  poisonous  action  of,  403 
Carboxyhsemoglobin,  403 
Cardiac  cycle,  232 
Cardiac  glandg,  507 
Cardiac  muscle,  70 

rhythm  and  conduction  in,  254 
Cardiac    nerves,    influence    on    blood-pressure, 

281 
Cardiac  orifice  of  stomach,  action  of,  551 

sphincter  of,  554,  556 

relaxation  in  vomiting,  ib. 
Cardiac  sympathetic,  251,  281 
Cardiogram  from  human  heart,  240 
Cardiograph,  238  et  seq. 
Cardio-inhibitory,  249 
Cardiometer,  Barnard's,  248 

Roy's,  ib. 

Cardiophonogram,  249 
Carotid  gland,  345 
Cartilage,  87  ct  s«/. 

articular,  38 

cellular,  40,  48 

chondrin  obtained  from,  88 


CEREBELLUM. 

Cartilage— continued. 

classification,  37 

costal,  88 

development,  39 

elastic,  37,  39 

fibrous,  37.    See  Fibro-cartilage. 

hyaline,  ib. 

matrix,  ib. 

ossification  in,  46 

perichondrium  of,  47 

Santorini's,  800,  802,  805 

structure,  37 

temporary,  38 

varieties,  37 

Wrisberg's,  800,  805 
Cartilages  of  larynx,  799 
Casern,  429,  479,  482.    See  Milk. 
Caseinogen,  429,  479,  480,  482,  483 
Catalysts,  328,  441,  442 
Cauda  equina,  648 
Caudate  nucleus,  688 
Cavity  of  reserve,  60 
Cell  division,  15 
Cells,  5  et  seq. 

amoeboid,  5 

blood.    See  Blood-corpuscles. 

bone,  43 

cartilage,  48  et  seq. 

central,  508,  509 

characteristics  of,  11 

ciliated,  24 

connective  tissue,  30 

contents,  8 

definition  of,  5 

division,  15 

epithelium,  22.    See  Epithelium, 

gustatory,  781 

hepatic,  528 

nerve,  182 

olfactorial,  786 

parietal,  510 

pigment,  30,  82 

structure,  7  et  seq. 

varieties,  15  et  seq. 

vegetable,  5, 12 

distinctions  from  animal  cells,  5  et  seq. 
Cells  of  Deiters,  794 

of  Kupffer,  528 

of  Purkinje,  187,  681 

of  Sertoli,  864 

Cellular  cartilage,  40.    See  Cartilage. 
Cellulose,  413,  549 
Cement  of  teeth,  56,  59 
Central  cells,  508,  509 
Centres,  nervous,  etc.    See  Nerve-centres. 

of  ossification,  45 
Centrifugal  machine,  452 

nerve-fibres,  143 
Centripetal  nerve-fibres,  144 
Centro-acinar  cells,  517 
Centrosome,  7,  10,  11,  16,  865 
Cerebellar  ataxy,  750 
Cerebellar  cortex,  section  of,  682 
Cerebellum,  680  et  seq. 

analysis  of,  165 

connections  of,  683 

effects  of  removal  or  disease,  750,  751 

equilibration,  751 

functions  of,  749  et  seq. 

grey  matter,  165,  186,  644,  680 

impulses,  751,  752 

peduncles  of,  682 

sections  of,  680,  681,  684 

semicircular  canals,  752,  754 

extirpation  of,  750, 756 

sensory  impulses,  751 


902 


INDEX 


CEREBELLUM. 

Cerebellum— continued 

stimulation,  750,  756 

structure,  680 
Cerebral  cortex,  186,  644,  696,  697,  725 

grey  matter  of,  687 

histological  structure,  695  et  seq. 

pyramidal  cells,  695 
Cerebral  hemispheres.    See  Cerebrum. 
Cerebral  nerves,  origin  of,  663  et  seq. 

See  under  names  of  nerves. 
Cerebral  vesicles,  primary,  645 
Cerebro-spinal  axis,  181 
Cerebro-spinal  fluid,  168,  644 
Cerebro-spinal  nervous  system,  181 

See  Brain,  Spinal  cord,  etc. 
Cerebrote,  437 
Cerebrum,  686  et  seq. 

convolutions  of,  690  et  seq. 

crura  of,  644 

degeneration  tracts   after  injury  of  Rolandic 
area,  728 

effects  of  injury,  ib. 
removal,  721 

external  capsule,  689 

extirpation,  727,  728 

functions  of,  721  et  seq. 
early  notions,  721 

grey  matter,  687,  690 

hemispheres,  686, 691-693, 704,  731,  733,  730,  741, 
742 

internal  capsule,  688,  689 

localisation  of  functions,  726 

motor  areas,  ib. 

relation  to  speech,  808 

sensory  areas,  728 
extirpation,  ib. 
stimulation,  727 

structure,  686  et  seq. 

white  matter,  698 
Ceruminous  glands  of  ear,  608 
Cervix  of  urinary  bladder,  570 
Chambers  of  the  eye,  819 
Chauveau's  dromograph,  287 
Chauveau's  apparatus  for  intracardiac  pressure, 

241 

Cheiro-kinaesthetic  area,  742 
Chemical    composition    of    the    human    body, 

406  et  seq. 
Chest,  expansion  In  inspiration,  854 

vertical  diameter  of,  ib. 

vital  capacity  of,  359 
Chest-voice,  806 
"  Chewing  the  cud,"  550 
Cheyne-Stokes'  respiration,  404,  405 
Child,  new-born,  and  changes   after  birth,  862 

1 1  seq. 

Chimpanzee's  brain,  781 
Chittenden  diet,  480,  481,  623 

important  character  of  his  work,  623 
Chlorides  in  urine,  595 

Chloroform,  action  on  cardiac  mechanism,  253 
Cholagogues,  535 
Cholalic  acid,  533 
Cholesterin  or  cholesterol,  9,  75,  166,  435,  436, 

534 

Choline,  166 
Chondrin,  88,  429 
Chorda  secretion,  502 
Chorda  tympani,  502,  504 
Chordae  tendinese.    See  Heart. 
Chorion,  887  et  seq. 
Chorionic  epiblast,  883,  884 
Chorionic  villi,  888,  889 
Choroid  coat  of  eye,  811 
Choroid  gland,  168 
Chromatic  aberration,  830 


COHNHEIM'S  EXPERIMENT. 

Chromatin,  10 

Chromatolysis,  193 

Chromatoplasm,  192 

Chromogen,  341 

Chromophanes,  847 

Chromophilic  material,  192 

Chromoplasm,  10, 11 

Chromo-proteins,  427,  430 

Chromosomes,  16  et  seq,  876 

Chrzonszezewski's  method  of  natural  injection, 

529 
Chyle,  226,  316,  547 

molecular  basis  of,  316 
Chyme,  554 
Cilia,  23,  24 
Ciliary  epithelium,  24 

function  of,  ib. 
Ciliary  motion,  25,  82 

nature  of,  25 
Ciliary  muscles,  812,  813 

action  of,  in  adaptation  to  distances,  825 
Ciliary  processes,  812,  813 
Cilio-spinal  centre,  721 
Circular  layer  of  heart,  212 
"  Circulating  protein,"  622 
Circulation  of  blood,  60,  227  et  seq 

action  of  heart,  213 

in  blood-vessels,  263  et  seq. 

in  brain,  312 

capillaries,  297 

course  of,  214  et  seq. 

effect  of  gravity  on,  279 

effect  of  respiration  on,  385 

erectile  structures,  313 

in  foetus,  891,  892 

influence  of  respiration  on,  385 
of  gravity,  279 

peculiarities  of,  in  different  parts,  312 

portal,  215 

pulmonary,  ib. 

renal,  ib. 

systemic,  3 

in  veins,  61 

velocity  of,  281 

Circulatory  system,  208  et  seq. 
Circumvallate  papillae  of  the  tongue,  779 
Clarke's  column,  650,  651 
Clasmatocytes,  81 
Claustrum,  688 

Cleavage  products,  18,  416,  417 
Clerk-Maxwell's  experiment,  841 
Clitoris,  313 

Clot  or  coagulum  of  blood.    See  Coagulation. 
Clupeine,  427 

Coagulation  of  blood,  60, 137,  446  et  seq. 
conditions  affecting,  447 
theories  of,  448 

of  milk,  482 

Coagulative  enzymes,  426,  439 
Cocaine,  490 
Coccygeal  gland,  345 
Cochlea  of  the  ear,  753,  791  et  seq. 

theories  in  connection  with,  767,  768 
Cochlear  division  of  auditory  nerve,  diagram  of, 

676 

Cochlear  nerve,  663 
Coefficient  of  oxidation,  395,  397,  398 
Coelom,  884 
Co-enzymes,  441 

Cognitive  mode  in  consciousness,  758 
Cohnheim,  areas  of,  65 

Cohnheim's    experiment    on    passage   of   blood- 
corpuscles,  298 

on  diabetes,  540 

on  erepsin,  525 

with  succus  entericus,  524 


INDEX 


903 


COITUS. 

Coitus,  881 
Collagen,  29,  40,  429 
Collateral  fissure,  694 
Colloidal  solution,  328,  423  n. 
Colloidg,  323,  424 
Colon,  the,  561 
Colostrum,  486 

corpuscles,  ib. 
Colour-blindness,  843 

testing  for,  844 
Colour-perception,  841 
Colour  reactions  of  proteins,  425 
Colour  sensations,  841 
Burch's  experiments,  844 
theories  of,  842 

Colours,  optical  phenomena,  841  et  seq. 
Columns  carnese,  211 
Columnar  epithelium,  21,  22,  529 
Coma,  diabetic,  405 
Combination- tones,  797 
Comma  tract,  654,  656 
Commissural  fibres,  648,  698 

nucleus,  679 

Common  path,  principle  of,  717 
Common  sensations,  775 
Complement,  the,  475 
Complemental  air,  359 
Complementary  colours,  842 
Compound  tubular  glands,  496,  497 

racemose  glands,  497 
Conative  modes  in  consciousness,  758 
Concha,  788 

Condiments  as  accessories  to  food,  490 
Conducting  paths  in  cord,  704  et  seq. 
Conduction,  law  of  axipetal,  191 
Conductivity,  172 
Cones  and  rods,  817 
movement  of,  847 
Conical    and    filiform    papillae   of   tongue,    779, 

780 

Coni  vasculosi,  864,  865 
Conjugate  deviation  of  head  and  eyes,  737 
Conjugated  proteins,  430 
Conjunctiva,  810 
Conjunctival  reflex,  711 
Connective  tissues,  28  et  seq. 
classification,  ib. 
corpuscles,  30 
elastic,  32 
fibrous,  ib. 

general  structure  of,  28 
jelly-like,  36 
retifonn,  35 
varieties,  30,  31 

Conscious  states,  physiology  of,  757  et  seq. 
Conservation  of  energy,  law  of,  630 
Consonants,  808 
Contractile  substance,  63 
Contractility  of  muscle,  81  et  seq. 
Contraction,  heat,  165 
Contraction  of  heart,  128,  232 
Contraction  of  pupil,  827 
Contraction,  Pfluger's  law  of,  174,  175 
Contrast  of  colour,  845 
Conus  medullaris,  648 
Convergence  of  eyes,  827 
Convoluted  tubes,  864 
Convolutions,  cerebral,  690  et  seq. 
Cooking,  effect  of,  489 
Coordination  of  muscular  movements,  107 
Copper  sulphate,  or  Piotrowski's  test,  425 
Copulation,  881 
Cord,  spinal.    See  Spinal  cord. 
Cornea,  811,  813 
corpuscles,  812 
Corneo-scleral  junction,  813,  814 


CYSTIC  DUCT. 

Coronary  arteries,  237 
Corona  radiata,  689 
Corpora  cavernosa,  313,  866 

quadrigemina,  663,  673,  681 
Corpus  Arantii,  214 
callosum,  686 
dentatum 
of  cerebellum,  681 
of  olivary  body,  ib. 
Highmorianum,  863 
luteum,  870,  880 
of  human  female,  ib. 
spongiosum,  313,  866 
striatum,  687 

Corpuscles  of  blood,  444.    See  Blood-corpuscles, 
Corpuscles,  Malpighian,  334 
Corpuscles,  of  Grandry,  768,  769 
of  Hassall,  336,  337 
of  Herbst,  766 
of  Meissner,  767,  774,  775 
of  Pacini,  766,  767 
Cortex,  181,  342,  644,  682,  695 
Corti  on  rotation  of  cell  sap,  13 
Corti,  organ  of,  793 
Cortical  retina,  736 
Cortico-pontine  fibres,  670,  700 
Cortico-spinal  fibres,  670,  70C 
Corti's  rods,  793 
Cotyledons,  889 
Coughing,  mechanism  of,  381 
Cowper'g  glands,  570 
Cranial  nerves,  664  et  seq. 
nuclei  of,  664,  665,  667,  670 
origin  and  functions  of,  673  et  seq. 
Creatine,  166,  420,  589-591,  894 
Creatinine,  590 
Cremasteric  reflex,  711 
Crescents  of  Gianuzzi,  499 
Cretinism,  cause  of,  338 
Crico-arytenold  muscles,  800-803 
Cricoid  cartilage,  799 
Crico-thyroid  muscle,  800 
Crista  acoustica,  753 
Crossed  hemiplegia,  729 
Crossed  pyramidal  tract,  655 
Crosses  of  Ranvier,  75 
Crowbar  accident,  738 
Crucial  sulcus,  730 
Crura  cerebelli,  664 
cerebri,  644,  673,  689 
grey  matter  of,  645 
Crusta, 673 

petrosa,  56,  59 
Crypts  of  Lieberkuhn,  493 
Crystallin,  814 
Crystalline  lens,  811,  813 
Crystallisable  proteins,  424 
Crystalloids,  424 
Cubical  epithelium,  21 
Cuneus  or  cuneate  lobule,  694 
Cuorin,  435 
Cupula,  753 

Curative  inoculation,  473 
Curdling  ferments,  482 
Currents  of  action,  121 
constant,  88 
demarcation,  123 
induced, 89 
of  rest,  121 
Cutaneous  sensations,  766  et  seq. 

varieties  of,  772 

Cuticle.    See  Epidermis,  Epithelium. 
Cutis  vera,  604 

Cybulski'g  haematachometer,  286 
Cyclopterine,  427 
Cystic  duct,  527 


904 


INDEX 


CVSTINK  IN  URINE. 


Cystine  in  urine,  598 
Cystine,  421,  422,  599 
Cytosine,  421 


D. 


Dalton-Henry  law  on  gases  in  the  blood,  362 
Daniell's  battery,  88 
Dark-adaptation  of  eye,  848 
Darwin,  858 

Deaf-mutes  and  equilibrium,  756 
Deamidases,  440 
Deamidation,  546 
Death,  895 
Decidua,  887 

basalis,  or  serotina,  887-889 
capsularls  or  reflexa,  887 
development  of,  888 
menstrualis,  873,  874 
reflexa,  or  capsularis,  887-889 
vera,  887,  888 
Decussation  of  fibres  in  medulla  oblongata,  068, 

669 

of  optic  nerves,  853 
Deep  sensibility,  774 
Defaecatlon,  mechanism  of,  562,  721 
centre,  721 

influence  of  spinal  cord  on,  563 
Deficiency  diseases,  491 
Degeneration  method,  148,  156,  178,  307 
tracts  of  descending,  655 

ascending,  657 

Deglutition.    See  Swallpwing. 
Deiters,  cells  of,  794 

nucleus,  670,  671,  677 
Delezenne  on  trypsinogen,  524 
Demarcation  current,  123 
Demilunes  of  Gianuzzi,  499 
Demoor's  sleep  theory,  746 
Dental  germ,  56 
papilla,  56,  58 
periosteum,  59 
Dentate  fissure,  694 
Dentate  nucleus,  669 
Dentine,  28,  54 
formation  of,  57 
structure,  54 
Depressor  nerve,  249,  305 
Dermis,  604 

Descemet's  membrane,  812,  813 
Descending  tubule  of  Henle,  567 
Development,  858  et  seq. 
adipose  tissue,  34 
blood-corpuscles,  459 
blood-vessels,  459 
bone,  40  et  seq. 
cartilage,  39 
decidua,  887 

embryo,  diagrams  of,  885,  887,  883 
fertilisation,  881 
foetal  circulation,  891 
foetal  membranes,  887 
impregnation,  881 
nerve-fibres,  83 
ovary,  879 
ovum,  875 
segmentation,  883 
teeth,  58 
Dextrin,  409,  412 
Dextrose,  407,  409,  411,  439,  440 
in  urine,  601 

tests  for  determining,  409,  410,  601,  602 
Diabetes,  409,  538,  539,  542,  778 

artificial  production  in  animals,  538,  539 
Diabetic  coma,  405 
Diabetic  puncture,  538 


EAR. 

Dialyser,  a,  424 
Dialysis,  324,  453 
Diamino-acids,  421 
Diamino-diphosphatides,  435 
Diamino-monophosphatides,  ib. 
Diapedesis  of  blood-corpuscles,  298 
Diaphragm.    See  Inspiration,  etc. 
Diastase  of  liver,  537 
Diastole  of  heart,  238 
Diastolic  pressure,  296 
Dlastolic  sound,  236 
Dicrotic  pulse,  294 
Diet,  613  et  seq. 
a  healthy,  480 
Chittenden's,  480,  481 
nutritive  value,  479  et  seq. 
Eanke's,  480 

tables,  480,  482,  613  et  seq. 
Voit's,  480 
Difference-tones,  797 
Diffusion  and  osmosis  distinguished,  323 
Digestion, 

in  the  intestines,  517  et  seq. 
mechanical  processes,  550  et  seq. 

See  Gastric  fluid,  Food,  Stomach. 
Dilator  pupillse,  812 
Dilemma,  720 
Dipeptides,  423 
Diphasic  variation,  123,  124 
Diphtheria  toxin,  474 
Diplococci,  439 
Diplopia,  850 
Direct  cerebellar  tract,  658 

pyramidal  tract,  ib. 
Disaccharides,  409 
Discus  proligerus,  869 
Disease,  "  germ  theory  "  of,  438 
Distributing  nerve-cells,  194,  195 
Disuse  atrophy,  148,  194 
Diuretics,  576 
Dixon  on  spermine,  878 
Dobie's  line,  65 
Dog,  " scratch"  reflex  of,  719 
Dog's  brain,  729 
nerves,  162,  303 
spleen,  335 

submaxillary  gland,  499 
Dorsal  cord,  165 
Double  vision,  850 

11  Drainage  "  theory,  M'Dougall's,  716,  717 
Dromograph,  Chauveau's,  287 
Drugs,  action  of,  775 
on  the  eye,  833 
on  the  heart,  253 
on  perspiration,  611 
Ductless  glands,  331  et  seq. 
theories  of  secretion,  331 
Ducts  of  Bellini,  566,  567 
Ductus  arteriosus,  893 

closure  of,  894 
venosus,  892 

closure  of,  894 

Dudgeon's  sphygmograph,  292 
Dupre"'s  urea  apparatus,  585 
Dynamometer,  114 
Dyne,  267 
Dyspnoea,  389 

E. 

Ear,  788  et  seq. 
bones  or  ossicles  of,  788 

function  of,  796 
development,  878 
external,  788 

function  of,  795 


INDEX 


905 


EAR. 
Ear—  continued 

internal  or  labyrinth,  790,  791 
function  of,  796 

middle,  788 

function  of,  795 
Ectopia  vesicae,  580 
Edridge-Green  lantern,  844 
Efferent  channels,  diagram  of,  701 
Efferent  nerves,  73, 143 

nerve-cells,  194 

projection  system,  698 
Eggs  as  food,  486 
Ehrlich's  side-chain  theory,  475 
Einthoven's  string  galvanometer,  121,  245 

nervous  factor  in  respiration,  376,  377 

third  heart  sound,  246 
Elastic  cartilage,  37,  39 

fibres,  87 

tissue,  32 
Elastin,  30,  429 
Electrical  currents  of  retina,  849 

nerves,  144 

phenomena  of  muscle,  116  et  seq.,  176 

variation  in  central  nervous  system,  743 

in  glands,  497 
Electricity, 

in  muscle,  116  et  seq.t  176 

nerve,  176 

Electrocardiogram,  243  et  seq. 
Electrodes,  non-polarisable,  118,  119 
Electrometer,    Lippmann's    capillary,   120,    121, 
124 

record,  124-126 
Electrotonus,  169  et  seq. 
Eleidin,  604 

Elementary  substances  in  the  human  body,  406 
Embryo,  858  et  seq.,  885  n.    See  Development. 
Embryo  chick,  diagram  of,  885 
Embryological  method,  651 
Embryonic  area,  883 
Emetics,  557 
Eminentia  teres,  663 
Emmetropic  eye,  828 
Emulsification,  416,  520 
Enamel  of  teeth,  55 

formation  of,  58 
Enamel  organ,  ib. 
Enchylema,  7 
End-bulbs,  7G7 
Endocardium,  209 
Endogenous  fibres,  740 
Endogenous  protein  metabolism,  622 
End-plates,  motorial,  70,  78 
Endolymph,  753,  793 
Endoneurium,  SO,  81 
Endothelial  cells,  226,  321 

layer,  218 

membrane,  222 
Endothelium,  21,  208,  222 
Energy,  law  of  conservation  of,  630  ct  seq. 
Enterokinase,  523,  524 
Enzyme  action, 

coagulation,  426 

inexhaustibility  of,  441 

law  of,  441 

optimum  temperature  of,  441 

reversibility  of,  442 

specificity  of,  441 
Enzymes,  426,  438  et  seq.,  448 
activation  of,  441 
catalytic  action  of,  442 
inexhaustibility  of,  441 
Eosinophile  cells,  457 
Bpiblast,  19,  883  et  seq. 

organs  formed  from,  886 
Bpicardium,  208 


EYEBALL. 

Epicritic  sensibility,  707,  774,  777 

Epidermis,  22,  604,  886 

Epididymis,  864,  865 

Epigastric  reflex,  711 

Epiglottis,  553,800,  801 

Epineurium,  76,  77 

Epithelium,  20  etseq.,  570,  604,  886,  887 

cells  of,  784 

chemistry  of,  27 
ciliated,  21,  23,  24,  81,  348 
columnar,  21,  22,  23 

compound,  21 

cubical,  i&. 

goblet-shaped,  21,  22 

nutrition  of,  26  . 

pavement,  21 

renal,  574 

simple,  21 

spheroidal,  23 

stratified,  22,  23,  26 

transitional,  21,  22 
Erectile  structures,  circulation  in,  313 

tissue  of  penis,  865 
Erection,  313,  314,  721 

cause  of,  314 

influence  of  muscular  tissue  in,  314 
Erepsin,  440,  524 
Erg,  267 

Ergograph,  Mosso's,  132 
Ergotoxin,  effect  of  on  salivary  glands,  503 
Erythrobla8ts,41,  460 
Erythro-dextrin,  412,  505 
Esbach's  albuminometer,  601 
Euglobulins,  600 
Eustachian  tube,  678,  789,  790,  795 

function  of,  795 

valve,  209,  893 
Ewald's  induction  coil,  92 
Ewald,  "  sound  picture  "  theories  of,  798 
Excitability  of  nerves,  172 

of  tissues,  81 

Exhaustion  in  asphyxia,  389 
Exogenous  fibres,  741 
Exogenous  protein  metabolism,  622 
Exostosis,  60 
Expiration,  355  et  seq. 

force  of  expiratory  act,  360 

influence  on  circulation,  355,  360 

mechanism  of,  355 

muscles  concerned  in,  356 

relative  duration  of,  357 
External  auditory  meatus,  789 
External  capsule,  689 
External  respiration,  392 
Extractives,  166,  453 
Extraventricular  nucleus,  688 
Eye,  810  et  seq. 

accommodation,  820,  824,  827,  831 

action  of  drugs  on  pupil,  833 

adaptation  of  vision  at  different  distances,  824 
et  seq. 

blood-vessels,  820 

causes  of  dilatation  and  contraction  of  pupil, 
834 

chambers  of,  820 

focus,  820,  821 

optical  apparatus  of,  820,  821 
defects  in,  828 

principal  point,  821 

refractive  media  of,  820 

resemblance  to  camera,  ib. 
Eyeball,  811 

blood-vessels  of,  820 

electrical  currents  of,  845 

muscles  influencing  movement,  849 

point  of  rotation,  850 


906 


INDEX 


EYEBALL. 

Eyeball— continued 

transverse  and  visual  axis,  851 

various  positions  of,  850 
Eyelids,  development  of,  810 
Eyes,  simultaneous  action  in  vision,  850 

F. 

Facial  nerve,  663,  675 

effects  of  paralysis  of,  675 

origin,  ib. 

relation  of,  to  expression,  ib. 
Faeces,  composition  of,  548 

quantity  passed,  549 
Fallopian  tubes,  24,  25,  871     . 
False  vocal  cords,  801,  805 
Falsetto  voice,  806 
Faradisation,  101, 104 
Far-point,  828 
Fat.    See  Adipose  tissue. 

action  of  bile  on,  535 
of  pancreatic  secretion,  523 

metabolism  of,  541,  616 

situations,  where  found,  33, 34 

synthesis,  542 

uses  of,  34 
Fatigue,  744 

in  nerves,  132 
Fats, 

absorption  of,  546 

acids  of,  414 

action  of  pancreatic  juice  on,  520 

chemical  constitution,  414 

decomposition  products,  415 

emulsification,  416 

metabolism  of,  616 

of  milk,  483 

sap  on  ili  cat  ion,  415 
Fatty  acids,  414 
Fehling's  solution,  601,  602 
Female  generative  organs,  867 

pronucleus,  876 

Fenestrated  membrane  of  Henle,  217 
Fenestra  ovalis,  788,  791 

rotunda,  788,  791 

action  of,  797 
Fermentation,  438 
Ferments,  440.  See  also  Enzymes  Blood,  Milk, 

Digestive  juices. 
Fertilisation,  881 
Fibres  of  Miiller,  815,  816 

of  Remak,  77 

of  Sharpey,  44 
Fibrils  of  muscle,  65 

of  nerve,  74 
Fibrin,  60,  61,  446 

ferment,  440,  449,  453 

formation,  447,  451 

reticulum  of,  447 
Fibrinogen,  60,  315,  448,  451,  453 
Fibroblasts,  80 
Fibro-cartilage,  37 

classification,  ib. 

development,  39 

white,  37,  38,  40 

yellow,  37,  39,  40,  41 
Fibrous  tissue,  28  et  seq. 

white,  29 

yellow,  30 

Fick  on  work  of  muscles,  115 
Fick's  spring  kymograph,  275,  276 
Fifth  cranial  nerve,  663,  674 
Filiform  papillae  of  tongue,  779  et  seq. 
Fillet,  668,  672 
Filtration,  319,  320,  324 
Filum  terminale,  648 


GALACTOSIDES. 

Fischer's  laboratory,  the  work  in,  416,  421 

theory  of  dropsy,  321 
Fishes,  circulatory  system  in,  230 
Fistula,  intestinal,  523 
Flechsig's  embryological  method,  740 
Fleischl's  haemoglobinometer,  471 
Fleming's  chromatin,  10 
Flesh  of  animals,  479 
Flicker,  836,  854 
Flour  as  food,  488 
Flourens'  experiment,  749 
Fluids,  swallowing,  552 
Fluids,  tension  of  gases  in,  362  et  seq. 
Fluoride  of  calcium,  40 
Focal  distance,  824 
Foetal  circulation,  891-893 
Foetal  membranes,  887 

development  of,  ib. 
Foetus,  885  n.,  886,  893 

circulation  in,  891 

communication  with  mother,  890 
Folin's  method  of  estimating  urea,  585 
Follicles,  Graafian.    See  Graafian  follicles. 
Follicles,  Meibomian,  496,  810 
Fontana,  spaces  of,  814 
Food,  479  et  seq. 

absorption  of,  543  et  seq. 

accessories  to,  490 

chemical  compounds  of,  479 

constituents,  unknown  but  essential,  491 

cooking,  489 

digestibility  of  articles  of,  479 
value  dependent  on,  ib. 

fluidity  of,  555 

heat-value  of,  635 

of  man,  479 

proximate  principles  in,  ib. 

vegetable,  ib.,  489 
Foramen  ovale,  893 

of  Magendie,  644 

of  Munro,  688 
Fore-gut,  886 
Formaldehyde,  425 
Formatio  reticularis,  667 
Formic  acid,  414 
Fornix,  688 
Fossa  ovalis,  209 
Fovea  centralis,  814,  818,  841 
Fovea  hemielliptica  et  hemispherica,  791 
Franck's  cannula,  273 
Frogs, 

circulatory  system  in,  230,  231 

corpuscles  of,  454 

gracilis  of,  160 

heart,  230,  231,  251,  259 

mucous  membrane,  547 

nerves,  251 

reflexes  in,  709 
Fromann's  lines,  75 
Frontal  lobe,  690,  692 
Fundus  glands,  508 
Fundus  of  eye,  836 

of  urinary  bladder,  570 
Fungiform  papillae  of  the  tongue,  779,  780 
Funiculus  cuneatus,  662,  665 
Funiculus  gracilis,  662,  665 
Funiculus  solitarius,  670,  678 
Furfuraldehyde,  533 
Furth,  on  muscle  proteins,  138,  139 
Fuscin  granules,  847 


G. 


Galactose,  410 
Galactosides,  166,  437 


INDEX 


907 


GALL- BLADDER. 

Gall-bladder,  532 

structure,  ib. 
Galvanism,  122 
Galvanometer,  117  et  seq.,  245 

the  string,  121,  245 
Gametes,  859 
Garagee,  photographic  spectrum  of  haemoglobin 

and  its  derivatives,  468,  469 
Ganglia,  180,196  et  seq.    See  Nerve-centres. 

sympathetic,  functions  of,  500,  502 
Ganglion  cells,  layer  of,  815 
Ganglion  of  Scarpa,  677 
Ganglion  spirale,  794 

trunci  vagi,  249 
Gases, 

extraction  from  blood,  364 

of  the  blood,  361  et  seq. 

in  the  lungs,  372 

of  plasma  and  serum,  453 

tension,  362 

Gaskell's  heart- block,  257 
Gastric  fistula,  507 
Gastric  glands,  493 
Gastric  juice,  507  et  seq. 

acids  in,  510 
test  for,  510,  516 

action  on  bacteria,  525 

action  on  food,  513 

artificial,  507 

composition  of,  510,  511 

pepsin  of,  511 

secretion  of,  509 
Gastrin,  522 

Gay-Lussac's  law  for  gases,  325 
Gehuchten,  van,  law  of  axipelal  conduction,  191 
Gelatin,  29,  40,  54,  429 
Generative  organs  of  the  female,  867 

of  the  male,  863 
Gennar,  line  of,  697,  736,  737 
Genu  of  internal  capsule,  690 
Gerlach's  network,  650 
Germ  plasm,  Weismanns',  861 
Germ  theory,  438 
Germinal  area,  883 

epithelium,  868,  871 

spot,  18,  19,  871 

vesicle,  ib. 
Giant  cells,  41 

Gianuzzi's  crescents  or  demilunes,  499 
Gibson,  third  heart  sound,  240 
Gilbert's  experiments,  748 
Gland  cells,  function  of,  496 
Glands.    See  names  of  different. 
Gliadin,  434 
Glisson's  capsule,  528 
Globln,  427,  463 
Globulins,  138,  165,  424,  427,  433,  600 

character  of,  515 

distinctions  from  albumin,  428 
Glomeruli,  567,  569,  573 

olfactory,  786 

Glosso-kinaesthetic  area,  741 
Glosso-pharyngeal  nerve,  663,  678 

communications  of,  678 

functions,  ib. 

motor  filaments,  ib. 

a  nerve  of  common  sensation  and  of  taste,  ib. 
Glottis,  movements  of,  551,  805 
Gluco-proteins,  427,  430 
Glucosamine,  430 
Glucose.    See  Dextrose. 

in  liver,  537 

test  for,  412 
Glutamic  acid,  422 
Gluteal  reflex,  711 
Glutelins,  433 


H^MODYNAMOMKTKR. 

Gluten,  488 
Glutenin,  ib. 
Glycerides,  414 
Glycerin  or  Glycerol,  415 

origin  of,  619 
Glycine,  417,  422 
Glycocholic  acid,  533 
Glycogen,  8,  407,  412,  413,  537,  538 

characters,  412 

destination  of,  537 

preparation,  ib. 

quantity  formed,  i&. 

source  of,  536 

variation  with  diet,  537 
Glycogenolytic  nerves,  541 
Glycolysis,  540 
Glycosuria,  538,  540 
Glycuronic  acid  and  sugar,  540 
Gmelin's  test,  533,  602 
Goblet  cells,  21,  22 
Goldman's  intra-vitam  staining,  890 
Golgi's  method,  186,  697,  746 
Goll's  column,  651,  654,  657,  660,  662 
Goltz,  experiments  on  the  cerebrum,  725 
"  Goose  skin,"  607 
Gotch,  experiments  on  heart,  248 

on  nerves,  159, 176 
Gowers'  haemoglobinometer,  470,  471 

tract,  657 

Gowers-Haldane  haemoglobinometer,  470 
Graafian  follicles,  869  et  seq. 

formation  and  development  of,  ib.  et  seq. 

relation  of  ovum  to,  870 

rupture  of,  changes  following,  870  et  seq. 
Gradient,  pressure,  285,  386 
Gramme-molecular  solutions,  323 
Grandry,  corpuscles  of,  768,  769 
Granular  layers  of  retina,  816 
Grape-sugar.    See  Dextrose. 
Graphic  method,  87 

Gravity,  influence  of,  on  circulation,  279 
Grey  matter  of  cerebellum,  180,  644,  680 

of  cerebrum,  181, 186,  688 

of  crura  cerebri,  645 

of  medulla  oblongata,  180,  667,  668 

of  spinal  cord,  181,  650 
Grossmann,  on  the  course  of  the  inhibitory  fibres 

in  mammals,  249,  252 
Ground  substance  of  connective  tissue,  81 
Growth  of  bone,  50 
Guanase,  594 
Guanine,  432 
Guanylic  acid,  ib. 
Gullet.    See  (Esophagus. 
Gustatory  cells,  781 
Gyrus  fornicatus,  694 

H. 

Haemacytometers,  458 
Hsemadromometer,  Volkmann's,  282 
Haematachometer,  Cybulski's,  286 

Vierordt's,  287 
Hsematin,  463 
Hsematoblasts,  334 
Hsematogens  of  cells,  431 
Haematoidin,  464 
Haematoporphyrin,  464,  582 
Haematoscope,  Herrmann's,  466 
Haematoxylin,  10 
Haemautograph,  295 
Hsemin,  463,  464 
Haemochromogen,  463 
Hsemodromometer,  282 
Haemodynamometer,  272 


908 


INDEX 


HAEMOGLOBIN. 

Haemoglobin,  61,  370,  424,  454 
analysis  of,  461 
and  carbon  monoxide,  403 
compounds  of,  465 
crystallisable,  424 

crystals  of,  and  how  to  obtain  them,  462 
dissociation  curve  of,  367,  370 
distribution,  461 
estimation  of,  470 

increase  in  the  blood  at  high  altitudes,  402 
photographic  spectrum  of,  468,  469 
reaction  with  oxygen,  367 
solution  of,  367,  368 
Hsemoglobinometers,  470,  471 
Hsemoglobinuria,  603 
Haemolymph  glands,  336 
Haemolysins,  475 
Haemopyrrol,  464 
Hair-cells,  754,  794 
Hair-folHcles,  605,  606 
Hairs,  605 

structure  of,  ib. 

Haldane's  apparatus  for  estimating  the  carbonic 
acid  and  aqueous  vapour  given   off  by  an 
animal,  393 
carbonic  oxide  method  of  estimating  oxygen 

tension  of  arterial  blood,  374,  375 
Haldane  and  Priestley's  method  in  dealing  with 

respiration,  375 

Haldane's  measurement  of  air  breathed,  358 
Haldane's  modification  of  Gowers'  haemoglobin- 

ometer,  445 

Hales'  investigations  on  blood-pressure,  271 
Hallucination,  764 
Hamburger's  experiments  with  Succus  entericus, 

523 

Hammer  bone,  788,  789 
Hamulus,  792 

Hannover's  stratum  intermedium,  58 
Haptophor  groups,  475 
Hardy,  microscopic  structure  of  cells,  8 
Harvey  on  circulation  of  the  blood,  227,  234 
Hassall,  concentric  corpuscles  of,  336,  337 
Hausmann's    method    of    analysing    proteins, 

423 
Haversian  canals,  42,  43 

lamella,  44      , 

Head's  experiments,  378,  379,  705 
Hearing,  anatomy  of  organ  of,  788  et  seq. 
influence  of  external  ear  on,  794 

of  middle  ear,  ib. 
physiology  of,  ib. 
range  of,  797 

See  Sound,  Vibrations,  etc. 
Heart,  208  et  seq. 
action  of, 
accelerated,  253 
force  of,  247 
frequency,  ib. 
inhibited,  253 
isolated,  260 
self-steering,  238 
auricles  of,  209-212 
block,  246,  257 
chambers,  209 

capacity  of,  212 

chordae  tendineae  of,  213,  234,  236 
columnse  carnese  of,  212 
conduction  in  the,  254 
course  of  blood  in,  214 
cycle,  232 
endocardium,  209 
excised  mammalian,  261 
force,  245 

frog's,  230,  231,  259 
nerves  of,  251 


HERTZ  ON  THE  PROCESS  OF  DIGESTION. 

Hear  t — continued 
ganglia  of,  255 

gaseous  exchanges  during  inhibition,  254 
influence  of  drugs,  253 

of  sympathetic  nerve,  251 
innervation,  249 
intracardiac  pressure,  240 
investing  sac,  208 
muscular  fibres  of,  68 
musculi  papillares,  214,  234 
nervous  system,  influence  on,  249 
output  of,  247 
pericardium,  208 
physiology,  232  et  seq. 
plethysmograph,  260 
reflex  inhibition,  253 
situation,  208 
size  and  weight,  212 
sounds  of,  235,  245,  246 


structure  of,  212 
valves,  210,  213 
auriculo-ventricular,  210-212,  234,  236 

function  of,  234 
semilunar,  210,  212,  214,  235 

function  of,  235 
structure,  209  et  seq. 
ventricles,  their  action,  209-212 
work  of,  247 

Heat,  animal.    See  Temperature, 
influence  of  nervous  system,  640 

of  various  circumstances  on,  637 
losses  by  radiation,  etc.,  638-641 
regulation  of,  640 
value  of  foods,  634 
variations  of,  636 
Heat  and  cold  spots,  773 
Heat  coagulation,  423,  424,  426 
Heat  contraction,  164 
Heat  production,  637,  638,  640 
Heat-rigor  of  muscle,  139 
Heat-value  of  food,  634 
Heidenhain's  researches,  320,  578,  579 
Held,  experiments  on  myelination,  740 
Helicine  arteries,  866 
Helicotrema,  792 
Heller's  nitric-acid  test,  601 
Helmholtz'a  induction  coil,  91,  92 
myograph,  87,  92,  104,  108 
phakoscope,  825 
resonance  theory,  798 
Helweg's  bundle,  656,  657 
Hemianopsia,  737 
Hemiplegia,  729 
Hemisection  of  spinal  cord,  659 
Hemispheres,  cerebral.    See  Cerebrum. 
Henle,  fenestrated  membrane  of,  219 
layer  of,  606 

on  muscles  of  the  larynx,  803 
sheath  of,  77 
tubule  of,  567 

Henry-Dalton  law  for  gases,  326 
Hensen's  line  or  disc,  65,  67 
Hepatic  artery,  527 
Hepatic  cells,  527 
colic,  535 
duct,  527 
glycogen,  615 
veins,  S27,  529 
Herbst,  corpuscles  of,  766 
Bering's  experiments  on  blood  circulation,  289 

290 

Bering's  theory  of  colour,  842,  843 
Herrmann's  current  of  rest,  122, 123 

haematoscope,  466 
Hertz  on  the  process  of  digestion,  555 


INDEX 


909 


HERZEN  ON  SUCCAGOGUES. 

Herzen  on  succagogues,  513 

Heterocyclic  rings,  421 

Heterotype  mitosis,  876 

Hexatomic  alcohols,  408 

Hexone  bases,  420 

Hexoses,  408 

Hill  (Croft)  on  inverting  enzymes,  443 

Hill  (Leonard)  on  the  circulation  of  blood  in 


brain,  313  et  seq. 
us,  the 


Hilus,  the,  317,  318,  332,  565 

Hippocampal  convolution,  689 

Hippocampus  major,  694 

Hippuric  acid,  594 

Hirudin,  451 

His,  bundle  of,  257 

His  on  growth  of  nerve-fibres,  148 

Histidine,  420 

Histone,  427 

Homoiothermal  animals,  636 

Homotype  mitosis,  876 

Hope's  experiments  on  heart  sounds,  237 

Hopkins'  test  for  lactic  acid,  516 

for  uric  acid,  592 

on  foods,  491,  627 
Hoppe-Seyler  on  proteins,  416 
Hormone,  521,  880 
Horopter,  852 
Hunger,  778 

Hurst,  "  sound-picture"  theories  of,  798 
Hiirthle's  manometer,  242,  276 
Huxley's  layer,  606 
Hyaline  cartilage,  38,  40,  45 
Hyaloplasm,  7,  14,  68,  83 
Hydrobilirubln,  534 
Hydro-kinetic  force,  284 

•static  force,  284 
Hydrolysis,  417,  514 
Hypermetropia,  828 
Hyperpnoea,  389 
Hypertonic  solutions,  327 
Hypoblast,  19,  883 
Hypogastric  nerves,  581 
Hypoglossal  nerve,  664,  679 

distribution,  679 

origin,  ib. 

Hypopituitarism,  345 
Hypotonic  solutions,  827 
Hypox»«ttiine,  166,  421,  432 
Hysteria,  808 

I. 

Idiosome,  865 

Illusion,  765 

Image,  formation  on  retina,  824 

Immunity,  472  et  seq. 

Impregnation  of  ovum,  881 

Inanition  or  starvation,  628 

Incoordination,  750,  756 

Incus,  or  anvil-bone,  789 

Indican,  596 

Indiffusibility  of  proteins,  424 

Indigo,  ib. 

Induction  coil,  89  et  seq. 

current,  89 
Infantile  paralysis,  770 

softness  of  head,  46 
Infundibulum,  351 
Inhibition,  vagus,  253 
Inhibitory  nerves,  144 
Inoculation,  curative,  473 

protective,  ib. 
Inogen, 138 
Inorganic  compounds  in  body,  406 

salts  in  nerve,  166 

salts  in  protoplasm,  9 


ISOMETRIC  CONTRACTION. 

Inosite,  166,  413 
Insalivation,  550 
Inspiration,  354,  378 

elastic  resistance  overcome  by,  ib. 

expansion  of  chest  In,  ib. 

extraordinary,  ib. 

force  employed  in,  251,  258 

mechanism  of,  354  et  seq. 

tracings  of  diaphragm,  379 
Instruments  for  demonstrating  muscular  action, 

87  et  seq. 
Intercellular  material,  4,  29 

passage,  351 
Intercentral  nerves,  145 

Intercostal  muscles,  action  in  inspiration,  355 
et  seq. 

action  in  expiration,  355 
Intercrossing  fibres  of  Sharpey,  44,  45 
Interglobular  layer,  55 
Interglobular  spaces,  57 
Interlobular  arteries,  569 

veins,  ib. 

Intermediary  nerve-cells,  194,  195 
Intermediate  areas,  742,  743 
Intermittent  pulse,  290 
Internal  capsule,  688 

importance  of,  ib. 

respiration,  392 
Internal  ear,  790 
Internal  secretion  theory  of  the  ductless  glands, 

331,  332 

Interstitial  cells,  44,  865 
Intestinal  fistula,  diagram  of,  523 
Intestinal  juice,  518  et  seq. 
Intestines,  492, 557  et  seq. 

digestion  in,  517  et  seq. 
duration  of,  563 

large,  560 
coats  of,  493 
glands,  494 
structure, ib. 
view  of,  561 

movements,  560 

mucous  membrane  of,  494 

nervous  mechanism,  558,  563 

small, 

coats  of,  493 
glands,  493,  494 
movements  of,  557 
structure,  493,  494 
Intracardiac  nerves,  252 

pressure,  240 

Intracellular  enzymes,  440 
Intra ventricular  nucleus,  688 
Intra-vitam  staining,  890 
Inversion,  410,  522 
Invertase,  522 
Inverting  enzymes,  440 
Involuntary  muscles,  62  (see  140  ct  seq.} 

structure  of,  62 
lodo-thyrin,  339 
Ionic  reactions,  328 
Iris,  812,  813 

angle  of,  814 

functions,  832 

motor  nerves,  diagram  of,  833 

reflex  actions,  ib. 
Irradiation,  830 
Irritability  of  tissues.  81  et  seq. 
Island  of  Bell,  688,  692 
Islands  of  Calleja,  675 
Islets  of  Langerhans,  517,  539 
Iso-cholesterin,  436 
Isolated  heart,  260 
I ao- maltose,  411 
Isometric  contraction,  115 


910 


INDEX 


ISOTONIC  CONTRACTION.  ' 

Isotonlc  contraction,  115 

solutions,  326 
Ivory,  54 

J. 

Jacksonian  epilepsy,  730 

Jacobsen's  nerve,  678 

Jaundice,  535 

Jecorin,  341 

Jelly-like  connective  tissue,  28,  36 

Jugular  ganglia,  249 

Juice,  gastric,  507 

K. 

Kaiser's  views  on  muscular  contraction,  115 
Karyokinesis,  16  et  seq. 

phases  of,  17 

Katabolic  nerve  groups,  203 
Katabollc  phenomena,  612 
Katabolism,  618,  619 
Katelectrotonus,  171, 173 
Rations,  322 

Kennedy,  experiment  on  nerve  crossing,  161 
Kent's  bridge,  257 
Kephalin,  166,  435,  438 
Kerasin,  488 

Keratin,  23,  27,  429,  436,  604 
Ketone,  407 
Ketoses,  408 

Key,  Du  Bois  Reymond's,  88 
Kidney  oncometer,  the,  571 
Kidneys,  561  et  seq. 

blood-vessels  of,  how  distributed,  569 

calyces,  565 

capillaries  of,  568 

diseases  of,  effect  on  the  skin,  611 

extirpation  of,  579 

function,  572.    See  Urine 

hilus  of,  565 

Malpighian  corpuscles  of,  566,  567 

nerves,  571 

oncometer,  ib. 

pelvis  of,  565 

plan  of,  ib. 

structure,  ib. 

tubules  of,  566  et  seq.,  569 

vascular  supply  of,  569 

weight,  565 

Kinsesthetic  sense,  776 
Kinetoplasm,  192 

Kjeldahl's  method  of  estimating  nitrogen.  585,  586 
Knee-jerk,  712 
Konig's  apparatus  for  obtaining  flame-pictures  of 

musical  notes,  807 
Kossel  on  protamines,  428 
Krause's  membrane,  65,  67 
Krogh's  tonometer,  363,  373 
Kiihne's  gracilis  experiment,  160 

muscle  plasma  experiment,  138 
Kupffer's  stellate  cells,  528 
Kyes  on  lecithin,  477 
Kymograph,  Fick's  spring,  275,  276 

diagrams  of  mercurial,  272,  274 

Ludwig's,  272,  273 

tracings,  275,  277 
Kymoscope,  Anderson  Stuart's,  271 


Labyrinth  of  the  ear.    See  Ear. 
Labyrinthine  impressions,  752 
Lacrimal  gland,  810 
Lact-albumin,  482 


LIVER. 

Lacteals,  225,  316, 
Lactic  acid,  166 

fermentation,  411 

tests  for,  516 
Lactiferous  ducts,  485 
Lactose,  407,  411,  483,  601 
Lacunae,  43,  570 
Laevulose,  408-410 
Lamellse  of  compact  bone,  44 
Lamellar  cells,  30 
Lamina  of  cortex,  696,  697 

cribrosa,  815 

spiralis,  792 

terminalis,  646 

Langerhans,  islets  of,  517,  539 
Langley  on  the  autogenetic  theory,  150,  151 
Langley's    experiment    on    vagus    and    cervical 
sympathetic  nerve,  161 

ganglion,  502,  504 

nicotine  method,  200 
Lanoline,  436 

Large  intestine.    See  Intestines. 
Laryngoscope, 803 
Larynx,  346,  347,  799  et  seq. 

anatomy  of,  799 

cartilages  of,  ib. 

diagrams  of,  805 

mucous  membrane,  801 

muscles  of,  801  et  seq. 

nerves  of,  803 

ventricle  of,  801,  805 

vocal  cords,  801 

movements  of,  804 
Lateral  sclerosis,  711 
Lateral  ventricle,  687 
Lateritious  deposit,  592 
Lawes'  and  Gilberts'  experiments,  618 
Layer,  papillary,  212 

circular,  ib. 

spiral,  213 

Lecithin,  9,  166,  435,  437,  477,  526 
Lee's  experiments,  755 
Lens,  crystalline,  812-814 
Lenticular  nucleus,  688 
Le  Page's  investigations  into  pancreatic  secre- 

tion,  520 

Leucine,  417,  418,  422 
Leucocytes.    See  Blood-corpuscles  (white). 
Leucocythaemia,  334,  593 
Leucosin,  433 

Levene  on  nucleic  acid  of  yeast,  432 
Lewis  on  hsemolymph  glands,  336 
Leydig's  theory  of  protoplasmic  structure,  7 
Lieberkiihn's  glands,  493,  494,  496,  497 
Liebermann's  reaction,  436 
Ligamentum  pectinatum  iridis,  813.  814 
Limbic  lobe,  694 
Line  of  Gennari,  697,  736,  737 
Lipase,  440,  513,  518,  617 
Lipoida,  9,  165,166,434 
Lipolytic  ferments,  440 
Lippmann's  capillary  electrometer,  120,  121 
Liquor  sanguinis,  or  plasma,  60,  444 
Lissauer,  tract  of,  657 
Listing's  reduced  eye,  821 
Litmus,  165 
Littre,  glands  of,  570 
Liver,  527  et  seq. 

bile,  528 

blood-vessels,  528,  529 

capillaries,  529 

cells  of,  528 

cirrhosis  of,  586 

circulation  in,  528 

diastase,  537 

extirpation  in  mammals,  539 


INDEX 


911 


LIVER. 

Liver — continued 

fat  metabolism,  541  et  seq. 

glycogenic  function  of,  536 

lobules  of,  527-529 

secretion  of.    See  Bile. 

structure,  528 

sugar  formed  by,  537,  538 

supply  of  blood  to,  527 

under-surface  of,  ib. 
"  Living  test-tube  "  experiment,  452 
Local  sign,  762 

Localisation  of  tactile  sensations,  770 
Locke's  solution,  262 
Locomotor  ataxy,  715 
Loeb  on  classification  of  ions,  323 

on  spermatozoon,  882 
Loewenthal's  tract,  656 
Loop  of  Henle,  567 
Lortet  on  the  carotid  flow,  289 
Loudness  of  voice,  806 
Lud wig's  graphic  method,  87 
Lud wig's  kymograph,  272,  273 
Lud  wig  on  the  lymph  flow,  319 

on  function  of  kidneys,  573,  577 

on   swaying   movements   of   small    intestine, 
557 

Stromuhr,  282 
Lugaro's  sleep  theory,  745 
Lunatic's  brain,  751 
Lungs,  346  et  seq. 

air-sacs  of,  351  et  seq. 

area  of  surface  of,  852 

blood-supply,  353 

capillaries  of,  352 

changes  of  air  in,  372 

circulation  in,  352 

coverings  of,  350 

diffusion  of  gases  within,  372 

lobes  of,  351 

lobules  of,  ib. 

lymphatics,  353 

muscular  tissue,  352 

nerves,  353 

nutrition  of,  352 

position  of,  346 

structure,  349 
Lunula,  605 
Lymph,  26,  32,  61,  70,  224,  315  et  seq. 

composition  of,  315 

current  of,  318 

nitration  theory,  319,  320 

formation  of,  26,  319 

path,  317 

relation  to  blood,  319 
Lymph  capillaries,  224 

origin  of,  226 

structure,  ib. 
Lymph-hearts,  structure  and  action  of,  318 

relation  to  spinal  cord,  ib. 
Lymphagogues,  320 
Lymphatic  glands,  36,  316  et  seq. 
Lymphatic  vessels,  208,  223  et  seq. 

of  arteries  and  veins,  221 

communication  with  blood-vessels,  224 

structure  of,  221 
Lymphocytes,  315,  456 
Lymphold  or  retiform  tissue,  28,  35     See  Adenoid 

tissue. 
Lysine,  420 

M. 

Macallum's  reagent,  27,  166 
Macdonald  on  nerves,  164,  166 
M'Dougall's  "  drainage  "  theory,  715,  716 
MacEwen  on  bone  regeneration,  50 
Macleod  on  the  nerves  of  the  liver,  641 


MEMHRANA. 

MacMunn,  use  of  the  term  myo-haematin,  138 
Macrophages,  457 
Macrosmatic  animals,  786 
Macula,  754 

lutea,  737,  814,  815,  818 
Magendie,  experiments  on  spinal  nerve-roots,  156 

foramen  of,  644 
Magnesium  phosphate,  40,  54 
Male  organs  of  generation,  863 

pronucleus,  881 

sexual  functions,  863 
Malleus  or  hammer  bone,  789,  790 
Malpighian  bodies  or  corpuscles  of  kidney,  566, 
567,569.    See  Kidney. 

corpuscles  of  spleen,  36,  334 
Malpighian  discovery  of  capillaries,  228 
Malpighian  layer,  604 
Maltase,  441 
Maltose,  411 ,  439,  441 
Mammal,  nerves  of,  248 
Mammalian  heart,  excised,  261 
Mammalian  ovum,  884,  886,  887 
Mammary  glands,  485 

evolution,  486 

involution,  ib. 

lactation,  ib. 

structure,  485 
Mannite,  408 
Mannose,  ib. 
Manometer,  Hlirthle's,  242,  276 

Martin's,  391 
Marchi  reaction,  168,  169 
Marchi's  method,  651 
Marey's  sphygmograph,  291 

tambour,  105,  107,  240 
Marrow,  41 

Martin's  sphygmometer,  295,  296 
Mast  cells,  30 
Mastication,  550 
Mastoid  cells,  788 
Maturation  of  the  ovum,  875 
Maximal  pulsation,  296 
Maxwell's  experiments  on  nerve  impulse,  163 
May,  Page,  reaction  of  degeneration,  179 
Mayer's  waves,  305 

Mayo's  experiments  on  cranial  nerves,  156 
Meat  as  food,  487 
Meatus  of  ear,  789 
Meckel's  ganglion,  678 
Mediastinum  testis,  864 
Medulla  oblongata,  180,  643  et  seq. 

decussation  of  fibres,  666-668 

diagrams  of,  668,  669 

dorsal  aspect,  666 

fibres  of,  how  distributed,  201,  662 

pyramids,  anterior,  661 
posterior,  ib. 

structure  of,  662 
Medullary  cavity,  41 

segments,  75 

sheath,  75  et  seq. 

substance,  340 
Meibomian  follicles,  496,  810 
Meissner's  corpuscles,  768,  774, 775 

plexus,  493 
Melanin  granules,  847 
Mellanby  on  creatine,  590 
Mem  bran  a, 

decidua,  837 

granulosa,  869 
development  into  corpus  luteum,  870 

hyaloidea,  819 

limitans  externa,  817-819 
interna,  815 

propria  or  basement  membrane.    See  Basement- 
membrane. 


912 


INDEX 


MEMBRANA. 

Membraua— continued 

tectoria,  792,  794 
action  of,  797 

tympaui,  788,  789,  792,  795 
Membrane,  vitelline,  871 
Membranes  of  the  brain  and  spinal  cord,  180 
Membranes,  mucous.    See  Mucous  membrane 

semipermeable,  325 

Membranous  labyrinth,  792,  793.    See  Ear. 
Memory  image,  764 

Mendel  and  Rockwood's  experiments,  546 
Meniere's  disease,  755 
Meningeal  streak,  312 
Menopause,  862,  874 
Menstruation,  862,  873 ,  874 

coincident  with  discharge  of  ova,  862 

corpus  luteum  and,  ib. 
Mercurial  air-pumps,  364 
Mercurial  kymograph,  272,  274 
Mesencephalon,  645 
Mesial  fillet,  672 
Mesoblast,  19,  29,  41,  75,  883  et  seq. 

organs  formed  from,  887 
Mesoblastic  somites,  883 
Metabolic  balance-sheets,  613  et  seq. 
Metabolism,  6,  541 

general,  612  et  seq. 

of  fat,  GIG  et  seq. 

of  protein,  621  et  seq. 
Metakinesis,  17, 18 
Meta-proteins,  433 
Metencephalon,  645 
Methsemoglobin,  465 

photographic  spectrum  of,  469 
Metschnikoff  on  inflammation,  298 

on  phagocytosis,  476 
Mett's  tubes,  516 
Meyer,  anaesthetics,  167 
Meyer,  "  sound-picture  "  theories  of,  798 
Meyer-Overton  on  narcotic  effect  on  cells,  331 
Meynert's  fountain  decussation,  673 
Micrococci,  439 
Micrococcus  ureae,  599 
Micro-organisms,  types  of,  439 
Microsmatic  animals,  786 
Micro-spectroscope,  467 
Micturition,  580 

centre,  580, 721 
Mid-brain,  644 

anterior  aspect,  661 

posterior  aspect,  ib. 

structure  of,  661  et  seq. 
Middle  ear.    See  Tympanum. 
Mid-gut,  886 
Milk,  as  food,  481,  482 

alcoholic  fermentation  of,  483 

chemical  composition,  472 

coagulation  of,  ib. 

fats  of,  483 
chemical  composition,  ib. 

globules  of  cow's  milk,  481 

proteins  of,  482 

reaction  and  specific  gravity,  ib. 

salts  of,  483 

secretion  of,  481 

souring  of,  483 
Milk-curdling  ferment,  520 
Milk-sugar,  411,  483 
properties  of,  411 
Milk-teeth,  50  et  seq. 
Millon's  reagent  and  test,  425 
Mitochondrial  sheath,  866 
Mitosis,  15,  876 
Mitral  cells,  785 
Mitral  valve,  211,  214 
Modiolus,  791 


MUSCLE. 

Molars.    See  Teeth. 
Molecular  layers,  816,  817 

reactions,  329 
Momentum,  267 

Monakow's  bundle,  657,  683,  685 
Monaster  stage  of  karyokinesis,  16,  18 
Monatomic  alcohols,  408 
Monkey's  brain,  730 

spinal  cord,  660 

Mono-amino  diphosphatides,  435 
Mono-ammo-mono  phosphatides,  435 
Monophasic  variation,  125 
Monoplegia,  729 
Monosaccharides.  409 
Monro-Kellie  doctrine,  313 

Moore  and  Rockwood's  experiments  on  fat  absorp- 
tion, 548 

Moore's  test  for  sugar,  410 
Morula,  883 
Mosso's  ergograph,  132 

experiments  on  the  effects  of  fatigue,  1 33 

experiments  on  micturition,  580 
Motor  areas  of  cerebrum,  728 

impulses,  transmission  in  cord,  709 

nerve-fibres,  73 
Motor  nerves,  70 

of  the  iris,  833 
Motor  oculi  nerve,  663, 673 

origin  of,  663 
Motorial  impressions,  751 

sense,  776 

Mountain  sickness,  400 
Movements  of  protoplasm,  11,  12,  82 

peristaltic,  of  involuntary  muscle,  140 

of  stomach,  555 
Mucic  acid,  410 

Mucigen  or  Mucinogen,  21,  27,  499 
Mucin,  21,  27,  430,  505 
Mucoids,  36,  430 
Mucous  membrane,  493 

gland-cells  of,  ib. 

of  intestines,  ib. 

of  larynx,  801 

of  stomach,  493 
MiiUer's  fibres,  815,  816 
Miiller's  fluid,  168 

Miiller's  law  of  specific  nerve  energy,  762 
Miiller's  muscle,  812,  813 
Multipolar  nerve-cells,  183  ct  seq. 
Munk's  experiments  on  fat  absorption,  548 
Munro,  foramen  of,  645,  688 
Murexide  test,  591 

Muscarine,  action  of,  on  the  heart,  253 
Muscle,  62  et  seq. 

blood-vessels  of,  70 

cardiac,  71,  255 

changes   in   form,    when   it   contracts,    86  ct 
seq. 

chemical  changes  in,  131 
composition  of,  136 

clot,  137 

columns,  65 

contractility,  68 

curves,  93,  96,  99, 101, 114 

development,  72 

dynamometer,  114 

elasticity,  108  et  seq. 

electrical  phenomena  of,  116  et  seq.,  176 

extensibility  of,  116  et  seq. 
fatigue,  effect  of,  97,  98,  132 

curves,  96 

Hensen's  line,  65,  67 
Involuntary,  62,  79  (see  140  et  seq.) 
irritability,  83 

evidence  of,  ib. 
lever  system  of,  106 


INDEX 


913 


MUSCLK. 

Muscle — continued 

nerves  of,  70 

plain,  71 

plasma,  137,  138 

proteins,  139 

reciprocal  action  of  antagonistic,  714 

red,  70 

response  to  stimuli,  84  et  seq. 

rigor,  136,  139 

sarcolemma,  63,  64 

sensory  nerve-endings  in,  769 

serum,  138 

shape,  changes  in,  104 

skeletal,  63 

sound,  developed  in  contraction  of,  104 

spindle,  70.    See  Neuro-muscular  spindle. 

stimuli,  85,  101 

striated,  structure  of,  66  et  seq. 

tetanus,  103  et  seq. 
negative  variation  of,  123 

thermal  changes  in,  129 

tonus, 113,  142 

twitch,  101  (see  123) 

voluntary,  62, 140  et  seq. 

wave,  100,  123 

work  of,  113 

Muscular  action,  conditions  of,  114 
Muscular  coat  of  alimentary  canal,  492 
Muscular  contraction,  84,  94,  96  et  seq. 

eflect  of  two  successive  stimuli,  101 
of  more  than  two  stimuli,  t&. 

voluntary  tetanus,  104 
Muscular  fibres, 

development,  72 

plain,  62  et  seq. 

transversely  striated,  ib. 

voluntary,  72 
Muscular  force,  111 

irritability,  81 

tissue,  62  et  seq. 

composition  of,  137 
Muscular  sound,  236 
Muscularis  mucosse,  348 
Musculi  papillares,  213,  214,  234 
Musical  sounds,  806 
Mydriatics,  833 
Myelencephalon,  645 
Myelination,  739 
Myelocytes,  461 
Myeloplaxes,  41 
Myogen-fibrin,  139 
Myogenic,  560 
Myoglobulin,  138 
Myohsematin,  ib. 
Myograph,  87,  92 

Helmholtz's,  92 

pendulum,  94 

spring,  ib. 

transmission,  105 
Myopia,  or  short-sight,  828 
Myorectes,  65 
Myoprotein,  139 
Myosin,  136  et  seq. 
Myosinogen,  137  et  seq. 
Myotics,  833 
Myxcedema,  338 


N. 


Nails,  605 

Narcosis,  744  et  seq. 

Nasal  cavities  in  relation  to  smell,  783  et  seq. 

Nasmyth's  membrane,  59 

Near  point,  826 


NERVES. 

Negative  variation,  121 
Neoencephalon,  646,  647 
Neopallium,  647 
Nerve-cells,  classification  of,  194 

structure  of,  182  et  seq. 

Nerve-centres,  180  et  seq.    See  Cerebellum,  Cere- 
brum, etc. 

ano-spinal,  564 

cilio-spinal,  721 

defalcation,  562 

deglutition,  551 

erection,  721 

micturition,  580,  721 

parturition,  721 

secretion  of  saliva,  500 

speech,  733 

vaso-motor,  300,  716 
Nerve-corpuscles,  176 

bipolar,  183 

unipolar,  ib. 
Nerve-fibres,  cardio-rahibitory,  249 

in  spinal  cord,  653 

intercentral,  145 
Nerve-impulse,  nature  of,  163 

velocity  of,  159 
Nerves,  73  et  seq. 

accelerator,  144 

action  of  stimuli  on,  81 

afferent,  73,  144,  204,  557 

analyses  of,  166 

axis-cylinder  of,  74 

axons,  152,  188, 198 

cells,  79, 181 

centrifugal,  143 

centripetal,  144 

cerebro-spinal,  181 

changes  in,  during  activity,  158 

classification,  143 

conductivity  of,  159 

cranial,  180, 181,  663  et  seq. 

crosses  of  Kanvier,  75 

crossing  of,  161 

degeneration,  146, 178,  307 
chemistry  of,  165 
reaction  of,  178 

direction  of  a  nerve  impulse,  160 

efferent,  73,  143,  657 

electrical,  144 
stimulation  of,  176 

excitability  of,  159 

fibres,  74  et  seq.t  143  et  seq. 
development  of,  79 

functions  of,  146 

funiculi  of,  76 

grey  matter,  73 

hypogastric,  581 

inhibitory,  144 

irritability  of,  81 

laws  of  conduction,  144  et  seq.,  159 

medullary  sheath,  74 

medullated,  74 

motor,  143 
termination  of,  78 

nodes  of  Ranvier,  75 

non-medullated,  77 

olfactory,  180,  663,  786 

physiology  of,  143  et  seq. 

pilo-motor,  607 

plexuses  of,  79 

reflex  actions,  145, 188 

secretory,  144 

section  of,  146,  500 

shocks,  method  of  slow  interrupted,  307 

size  of,  77 

spinal.    See  Spinal  nerves. 

stimulation  of  cut,  146 


914 


INDEX 


NERVES. 

Nerves — continued 

structure,  74 

sympathetic,  influence  on  heart,  249 

taste,  781 

temperature,  influence  of,  308 

terminations  of, 
in  corpuscles  of  Golgi,  769 
in  corpuscles  of  Grandry,  768 
in  corpuscles  of  Herbst,  766 
in  end-bulbs,  767 
in  motorial  end-plates,  78 
in  networks  or  plexuses,  770 
in  Pacinian  corpuscles,  766 
in  touch-corpuscles,  767 

trophic,  144 
Nervous  circles,  715 
Nervous  system, 

autonomic,  196  et  seq. 

central,  640,  642  et  seq. 

cerebro-spinal,  181 

electrical  variation  in  central,  743 

influence  on  the  heart,  389 

sympathetic,  249 

vaso-motor,  300  et  seq. 
Nervous  tissues,  chemistry  of,  165  et  seq. 

chemical  changes  during  activity,  167 

chemical     changes     in    degenerative     condi- 
tions, 167 

potassium  salts  in,  166 
Nervus  erigens,  581 
Neurilemma,  74, 153, 181 
Neuroglia,  181,  649 
Neurokeratin,  75,  165,  182,  429 
Neuro-muscular  spindles,  70,  769,  770 
Neuron,  189 
Neutral  sulphur,  595 
New-born  child   and   changes   after  birth,   862 

et  seq. 

Nicol's  prism,  68,  434 
Nicotine,  action  of,  200 
Nipple,  th9,  485 
Nissl's  granules,  165, 184,  192,  194 

significance  of,  192 
Nitric  oxide  haemoglobin,  465,  470 
Nitrogen  in  the  blood,  362 

eliminated  in  the  form  of  urea,  479 
Nodal  point,  820 
Nodes  of  Ranvier,  75 
Noll,  nerve  degeneration,  167 
Normoblasts,  460 
Nose.    See  Smell. 
Notochord,  884,  885,  886 
Nuclear  layers,  816,  817 
Nuclear  membrane,  9 

sap  or  matrix,  9, 10 
Nuclease,  432,  594 
Nucleic  acid,  431,  432 
Nuclein,  8,  10,  430 
Nuclei  pontis,  664 
Nucleoli,  9, 10, 12,  15 
Nucleo-proteins,  8,  Io5,  427,  430,  431 
Nucleotides,  432 
Nucleus  of  animal  cell,  5,  7,  9  et  seq. 

chemical  composition,  10 

division,  15 

of  cranial  nerves,  diagram  of,  665 

staining  of,  10 

structure,  ib. 

Nucleus  ambiguus,  669,  670,  678 
Nucleus  cuneatus,  667,  669 

gracilis,  ib. 
Nucleus  of  Bechterew,  677 

of  Deiters,  670,  671,  677 
Nutrition,  effect  on  respiration,  392 
Nyctalopia,  849 
Nystagmus,  ib. 


OVO-MUCOID 

o. 


Occipital  convolutions,  693 

Occipital  lobe,  690,  692,  693 

O'Donoghue  on  corpus  luteum,  881 

Odontoblasts,  53,  55,  57 

Odontogen,  57 

Odours,  786.    See  Smell. 

(Ersted's  electro-magnetism,  117 

(Esophagus,  492,  493 

CEstrus,  874 

Oleaginous  principles,  414 

Oleic  acid,  ib. 

Olein,  35,  414 

Olfactory  bulb,  784 

cells,  to. 

glomeruli,  786 

nerves,  663,  785,  786 

tract,  784 

"roots"  of,  ib. 

Olivary  body,  661,  668,  671,  681 
Oliver's  method  of  estimating  haemoglobin,  472 
Oncograph,  Roy's,  310 
Oncometer,  309,  571 

Roy's,  310,  571,  572 
Oiicytes,  868  et  seq. 
Oogenesis,  873,  877 
Oogonia,  871 

Ophthalmometer,  Helmholtz's,  826 
Ophthalmoscope,  836  et  seq. 
Opsonins,  476 
Optic  disc,  814 
Optic  nerve,  663,  815 

decussation  of  fibres  in,  853 

fibres,  815 

nervous  paths  in,  853 
Optic  radiations,  737 
Optic  thalamus,  689 
Optical  angle,  822,  823 

apparatus  of  eye,  820 
defects  in,  828 

axis,  822 

defects  in,  828 
Optogram,  847 

Ora  serrata  of  retina,  814,  815,  819 
Orang's  brain,  691 
Orbicularis  muscle,  810 
Orbital  sulcus,  691 
Organ  of  Corti,  794 

Organic  compounds  in  body,  406  et  seq. 
Ornithine,  417,  583 
Osazone, 412 
Osmosis,  323,  324-6 

distinguished  from  diffusion,  424 
Osmotic  pressure,  method  of  estimating,  322  et  seq. 

calculation  of,  326 

determination  of,  326 

of  proteins,  327 

phenomena,  322  et  seq. 

physiological  applications,  326 
Os  orbiculare,  790 
Osseous  labyrinth,  790.    See  Bar. 
Ossicles  of  the  ear,  788,  795 

action  of,  796 

Ossification,  stages  of,  45  et  seq. 
Osteoblasts,  45  et  seq. 
Osteoclasts,  49,  50 
Osteogen,  45 
Ovarian  ovum,  870 
Ovariotomy,  879 
Ovary,  867  et  seq.,  878,  879 

Graafian  follicles  in,  869,  870 

internal  secretions  of,  878 
Oviduct,  or  Fallopian  tube,  867 
Ovo-mucoid,  430 


INDEX 


915 


OVULATION. 

Ovulation,  869,  874 
Ovum,  18,  19,  870,  885  n. 

action  of  seminal  fluid  on,  875  et  seq 

changes  In  ovary,  875 
previous  to  fecundation,  875 

cleaving  of  yolk,  883 

development,  882 

diagrams  of,  868,  870  et  seq. 

fertilised,  881 

formation  of,  870 

germinal  vesicle  and  spot  of,  IS,  19,  870,  871 

impregnation  of,  881 

maturation,  875  et  seq. 

segmentation,  883 

structure  of,  870 
in  mammals,  871 

subsequent  to  cleavage,  883  ct  seq 
Oxidases,  440,  594 

Oxidation,  measurement  of  coeilicient  of,  396,  397 
Oxygen  in  the  blood,  365  et  seq.,  399  et  seq. 

pressure  of,  where  fatal,  400 

want,  399 

Oxyhaemoglobin,  61,  216,  372,  402,  461,  462,  465, 
469 

crystals  of,  462 

spectrum  of,  468,  469 
Oxyntic  cells,  508,  510 


P. 


Pacinian  corpuscles,  766,  767 
Pam,  777 

Pain  spots,  772,  774 
Pala-encephalon,  646,  647 
Palmitic  acid,  414 
Palmitin,  34,  414 
Pancreas,  517 

adaptation  of,  522 

extirpation  of,  539 

diabetic  condition  produced  in  animals  by, 
539 

so-called  peripheral  reflex,  secretion  of,  520 

structure,  517 
Pancreatic  juice,  518 

action  on  fats,  520 

composition  and  action,  518 

ferments  in,  ib. 
Papillje, 

of  the  kidney,  565 

of  skin,  distribution  of,  604 

of  tongue,  779  et  seq. 
Papillary  layer  of  heart,  212 
Paradoxical  contraction,  172 
Paralytic  secretion,  503 
Paramyosinogen,  138, 142,  165 
Paraplasm,  8 
Parathyroids,  339 
Parietal  cells,  508,  510 
Parietal  layer  of  pericardium,  208 
Parietal  lobe,  692,  693 
Parieto-occipital  fissure,  692,  694 


Parotid  gland,  503 
alveoli  of,  500 


Pars  ciliaris  retinae,  819 
Pars  intermedia,  343 

of  Wrisberg,  675 
Parthenogenesis,  878 
Parturition,  893-895 
Par  vagum.    See  Pneumogastric  nerve. 
Pathological  conditions  of  nervous  system,  811 
Pathological  urine,  600 
Pathogenic  organism,  476 
Patrick's  experiments,  748 

Pavy'g   views  as  to   the   liver  being   a    sugar- 
forming  organ,  537 


PINNA. 

Pawlow's  method  for  obtaining  pure  gastric  juice, 
511,  512,  522 

his  observations  on  the  salivary  glands,  504 
on  the  secretory  nerves  of  the  pancreas,  521 
on  the  succus  entericus,  523,  525 
Peduncles  of  the  cerebellum,  643 
Peduncles,  superior  cerebellar,  658 
Pelvis  of  the  kidney,  565 
Pendulum  myograph,  94,  95 
Penis,  structure,  866 
Pentosuria,  602 
Pepsin,  439,  440,  510 
Pepsinogen,  509 
Pepsin-hydrochloric  acid,  511 
Peptides,  422 
Peptogens,  513 
Peptolytic  enzymes,  440 
Peptones,  417,  433,  450,  601 

characters  of,  515 
Peptonuria,  601 
Perforated  spots,  689 
Perforating  fibres  of  Sharpey,  44 
Pericardium,  208 
Perichondrium  of  cartilage,  47 
Perilymph,  or  fluid  of  labyrinth  of  ear,  753,  790 
Perimeter,  839 
Perineurium,  76,  77 
Periosteum,  42,  45,  50,  59,  60 
Peripheral  resistance,  264  et  seq.,  297 
Peristalsis,  83,  140,  555,  559,  561 
Peristaltic  movements  of  intestines,  83,  557 

of  involuntary  muscle,  140  (see  553) 

of  stomach,  553  et  seq. 
Peritoneum,  209 
Permanent  teeth.    See  Teeth. 
Personal  equation,  720 
Perspiration,  cutaneous,  609 

insensible  and  sensible,  t&. 

ordinary  constituents  of,  610 
Pes,  673 

Petit's  canal,  820 
Pettenkofer's  reaction,  533 
Peyer's  patches,  36 
Pfliiger's  law  of  contraction,  174, 178 

on  hepatic  cells,  530 

on  menstruation,  875 

on  proteins,  622 
Phagocytes,  457,  473, 476 
Phakoscope,  Helmholtz's,  825 
Pharynx,  492,  805 
Phenyl  alanine,  418 
Phenyl-hydrazine  test,  412,  602 
Phloridzin-diabetes,  540 
Phosphates  in  urine,  596,  589,  600 
Phosphatides,  166,  167,  438 
Phospho-proteins,  427,  429 
Photo-chromatic  interval,  848 
Photo-haematochometer,  286 
Photophobia,  849 
Phrenograph,  357 
Physical  chemistry,  322  et  seq. 
Physiological  applications  of  physical  chemistry, 
327 

methods,  1  ft  seq. 

pit,  838 

rheoscope,  127 

zero,  774 

Pia  mater,  182,  644 
Picric  acid  test,  602 
Pigment  cells,  30 

of  retina,  82,  818 

movement  of,  847 

Pilocarpine,  effect  of,  on  salivary  gland,  503 
Pilo-motor  nerves,  607 
Pineal  gland,  345,  665 
Pinna,  789 


916 


INDEX 


PIOTROWSKI'S  REACTION. 

Piotrowski's  reaction,  425 

Piper's  experiments  on  muscle  contraction,  106 

Pitch  of  voice,  794,  806,  807 

Pitot's  tube,  286 

Pituitary  body,  343  et  seq. 

effects  of  removal,  345 
Placenta,  maternal,  889 

foetal,  i&. 
Plantar  reflex,  711 
Plasma  cell,  29 
Plasma  of  blood,  60,  444,  449,  452  et  seq. 

gases  of,  453 

Plasmatic  membrane,  330 
Plethysmograph,  308 

Schafer's,  260 
Pleura,  209,  349 
Plexus,  terminal,  770 

of  Auerbach,  79 

of  Meissner,  493 
Pneumogastric  nerve,  249  et  seq.,  664,  678 

distribution  of,  678 

functions,  664,  678 

influence  on 
deglutition,  553 
gastric  secretion,  512 
heart,  249 

muscles  of  stomach,  556 
pancreatic  secretion,  520 
vomiting,  556 

mixed  function  of,  678 

origin,  ib. 

Poehl  on  testis,  878 
Poggendorf's  rheochord,  170 
Pohl's  commutator,  169 
Poikilothermal  animals,  636 
Poiseuille's  hsemodynamometer,  272 
Polarimeter,  434 
Polygonal  epithelium,  529 


Polymorphic  layer,  697 
Polynuclear  leucoc 


Polynuclear  leucocytes,  456 
Polypeptides,  417,  422,  433 
Polysaccharides,  409 
Pons  Varolii,  642,  643,  646,  662 

grey  matter  in,  644 
Popielski's  investigations  into  pancreatic  secre- 

tion, 520 
Portal  canals,  528 

circulation,  215 

vein,  527,  528.  See  Liver. 
Postero-lateral  column,  658 
Post-ganglionic  fibres,  198  et  seq.,  249,  303 
Potato  starch,  grains  of,  412 
Precipitants  of  proteins,  426 
Precipitin,  477 

Precuneus  or  quadrilateral  lobule,  694 
Preganglionic  fibres,  198  et  seq.,  302 
Pregnancy, 

corpus  luteum  of,  870 
Prepyramidal  tract,  657 
Presbyopia,  831 
Pressor  nerves,  305 
Pressure  gradient,  285,  386 
Pressure  head,  286 
Pressure-measurers,  267 
Pressure,  positive  and  negative,  271 
Primary  areas,  742 
Primary  areolae,  48 
Primary  responses  of  eye,  848 
Primitive  nerve-sheath,  or  Schwann's  sheath,  78 
Primitive  gut,  886 
Projection  fibres,  698,  740 
Projection  systems,  698,  700 
Proline,  421 
Pronucleus,  female,  876,  882 

male,  876,  881,  882 
Propeptone,  514 


Pus  IN  THE  URINE. 

Prosecretin,  521 

Proseucephalon,  645 

Prostate  gland,  570,  879 

Prosthetic  group,  430 

Protagon,  437 

Protamines,  427 

Protective  inoculation,  473 

Protein -hydrolysis,  432 

Protein  metabolism,  6,  416,  621 

Proteins,  6,  8,  10,  165,  416  et  seq.,  453 

absorption  of,  544 

action  on  polarised  light,  425 

of  blood,  453 

Bence-Jones',  601 

classification,  426  et  seq. 

cleavage  products,  416 

coagulated,  426 

colloidal  solution,  424 

colour  reactions,  425 

composition,  416 

conjugated,  427,  430 

crystallisation,  424 

enzyme  coagulation,  440 

heat  coagulation,  425 

in  food,  479  et  seq. 

indiffusibility  of,  425 

metabolism  of,  6,  621  et  seq. 

osmotic  pressure  of,  327 

of  plasma,  453 

precipitants  of,  417,  425,  426 

of  serum,  453 

simple,  416 

solubilities,  423,  424 

in  urine,  600 
Protensity,  763 
Proteoclastic  enzymes,  440 
Proteolytic  enzymes,  440,  514 
Proteoses,  417,  433,  601 

characters  of,  515 
Prothrombin,  449 
Protones,  427 

Protopathic  sensations,  706,  774,  777 
Protoplasm,  5,  7, 10 

chemical  structure,  8 

irritability,  13 

movements,  8,  11  et  seq. 
Proto- vertebrae,  884 
Protrusion  of  eyeball,  849 
Przibram,  Hans,  theory  of  classification  by  muscle 

proteins,  139 
Pseudopodia,  11,  14 
Pseudoscope,  856 
Pseudo-stomata,  222 
Psycho-physical  parallelism,  758 
Ptosis,  850 
Ptyalin,  439,  499,  505 
Ptyalinogen,  499 
Puberty,  862 
Pulmonary  artery,  215 
Pulmonary  circulation,  pressure  in,  281 
Pulsation,  maximal,  296 
Pulse,  anacrotic,  293 

arterial,  290  et  seq. 

dicrotic,  293,  294 

intermittent,  290 

velocity,  ib. 

venous,  299 

volume,  309 

water  hammer,  291 

wave,  295 

Pupil  of  the  eye,  833,  834 
Purine  bases,  421,  432,  593 
Purkinje's  cells,  187,  681 

fibres,  71,  72,  213,  256,  257 

figures,  835 
Pus  in  the  urine,  603 


INDEX 


917 


PYLORIC  GLANDS. 

Pyloric  glanda,  507,  508 

orifice,  553,  554 
Pyramidal  tracts,  655 
Pyramids  of  medulla  oblongata,  661 

of  kidney.    See  Kidney. 
Pyrimidine  bases,  421 
Pyrrhol  blue,  890 
Pyrrolidine  derivatives,  421 

R. 

Racemose  glands,  496 
Kami  communicantes,  196 
Ranke's  diet,  394,  628 
Ranvier's  clasmatocytes,  31 
Ranvier's  crosses,  75 
Ranvier's  nodes,  ib. 
Raynaud's  disease,  312 
Reaction  time  in  man,  720 

velocity,  328 

Reactions  of  proteins,  colour,  425 
Receptive  groups,  475 

substances,  164 
Recurrent  sensibility,  156 
Rectum,  the,  562 
Red  marrow,  41 
Reduced  eye,  821 
Reductases,  440 
Reflex  arc,  711 

actions,  145,  188,  709  et  seq. 

inhibition  of,  253,  719 

in  frog,  709 

in  man,  145,  711 
superficial,  711 
tendon,  712 

of  dog,  719 

of  nerves,  145 

of  spinal  cord,  709  et  seq. 

"  scratch,"  719 
Reflex  secretion,  504 
Reflexes, 

cumulation  of,  710 

inhibition  of,  ib. 

spinal  visceral,  721 

spreading  of,  710 

uterine,  722 

Refraction,  laws  of,  821 
Refractive  media  of  eye,  ib. 
Reid,  osmotic  pressure,  828 
Reil,  island  of,  688,  692,  694 
Reissner's  fibre,  644 
Reissner's  membrane,  792,  794 
Relaxation  of  heart,  232 
Remak,  fibres  of,  77 

ganglion  of,  255 
Renal  circulation,  215,  580 

epithelium,  577 

oncometer,  572 

plexus, 571 

Rennet  or  rennin,  440,  483,  514 
Reproductive  organs,  6,  858  et  seq. 

development  of,  858  ct  seq. 

female,  867  et  seq. 

male,  863  et  seq. 

physiology  of,  872  et  seq. 
Requisites  of  diet,  613 
Reserve  air,  359 
"  Reserve  force,"  625 
Residual  air,  359 
Resistance,  peripheral,  264 
Resonance  theory,  798 
Respiration,  346  et  seq. 

abdominal  type,  355 

adaptation  to  high  altitudes,  401 

alteration  in  atmospheric  pressure,  362 

artificial,  383 


RHEOCHORD. 

Respiration — continued 

breathing  or  tidal  air,  359 

cause  and  regulation  of,  375  ct  seq. 

chemical  cause  of,  380 

chemistry  of,  ib. 

Cheyne-Stpkes,  404,  405 

effect  on  circulation,  385 

effect  on  nutrition,  392 

gases  in  relation  to,  361  et  seq. 

at  high  pressure,  402 

influence  of  nervous  system,  376 

intensity  of,  399 

mechanism  of,  354  et  seq. 

movements,  356 

nervous  factor  in,  376 
of  vocal  cords  in,  804 

quantity  of  air  changed,  358 

record  of,  356 

tissue,  397 

Respirations,  number  of,  in  healthy  person,  359 
Respiratory  acts,  special,  381 

apparatus,  346 

capacity  of  chest,  359 

centre,  375 
methods  of  recording,  356 

muscles,  354  et  seq. 

muscular  force  of,  360 

nerve-centre,  376 

rate,  360 
relation  to  pulse-rate,  ib. 

rhythm,  388 

sounds,  357 
"  Rest  cure,"  625 
Restiform  bodies,  661,  669 
Rete  mucosum,  604 
Rete  testis,  864,  865 
Reticulum,  7, 18 

of  the  thymus,  337 
Retiform  tissue,  28,  85 
Retina,  811,  814 

blind  spot,  834,  849 

blood-vessels,  820 

changes  in,  during  activity,  847 

duration  of  impression  on,  836 
of  after-images,  844 

electrical  variations  in,  849 

elements  of,  schema,  81(» 

excitation  of,  836 

focal  distance  of,  824 

fovea  contrails,  835 

functions  of,  834 

identical  points  of,  852 

image  on,  how  formed  distinctly,  823 

layers,  815  et  seq. 

meaning  of  term,  845 

nervous  elements  of,  816 

ora  serrata,  814 

pigment-cells,  82,  818 
movement  of,  847 

in  relation  to  single  vision,  850 

structure  of,  818 

visual  purple,  847 
Retinitis  pigmentosa,  849 
Retinoscope,  831 
Retraction  of  eyeball,  849 
Retractor  lentis  muscle,  828 
Reversibility,  329 
Reymond,  l5u  Bois, 

currents  in  muscle  prism,  121-123,  125,  126 

electrical  variation  in  spinal  cord,  743 

induction  coil,  90 

key,  88,  89 

non-polarisable  electrodes,  119 

spring  myograph,  94 
Rheochord,  174 

Poggendorfs,  170 


918 


INDEX 


RHEOSCOPE,  PHYSIOLOGICAL. 

Rheoscope,  physiological,  127 
Rheoscopic  frog,  127 
Rhodopsin  or  visual  purple,  847 
Rhythm  in  cardiac  muscle,  255 
Rhythmical  contraction  and  dilatation,  299 
Rhythmicality  of  movement,  83, 140 
Ricin,  475 
Rigor  mortis,  136  et  seq. 

affects  all  classes  of  muscles,  186 

phenomena  and  causes  of,  ib. 

physical  basis  of,  131 
Rima  glottidis,  801,805 
Ringer's  investigations  on  drug  action,  260 

fluid,  577 

solution,  260 
Ritter's  tetanus,  176 
Rocci,  Riva,  his  sphygmometer,  295 
Rods  and  cones,  817 
Rolandic  area,  687,  689,  722,  723,  727,  733 

injury  of,  723 
Rolando,  fissure  of,  692-694,  729,  732 

substantia  gelatinosa  of,  667,  668 

tubercle  of,  667 

Rollett's  view  of  the  red  corpuscles,  454 
Rose's  test,  425 

Rosel  on  protoplasmic  movement,  13 
Rotation,  13 

method  for  estimating  specific  gravity  of  blood, 

444 
Roy's  cardiometer,  248 

oncograph,  310 

oncometer,  ib. 
Rubner,  on  action  of  food  stuffs,  625 

law  of  conservation  of  energy,  630 
Rumination,  550 
Rut,  894 
Rutherford's  "  sound-picture  "  theories,  798 


Saccharic  acid,  410 

Saccharoses,  409 

St  Martin,  Alexis,  case  of,  507,  554 

Saccule,  791 

Salathe,  effect  of   gravity   on    the   circulation, 

279 
Saliva,  499,  504  et  seq. 

action  of,  505 

composition,  504 

process  of  secretion,  ib. 

reflex  secretion,  ib. 

secretion  following  stimulation  of  nerves,  500 

et  seq. 
Salivary  glands,  498  et  seq. 

digestion,  506 

extirpation  of,  504 

influence  of  nervous  system,  502,  503 
effect  of  drugs  on,  503 
secretory  nerves  of,  502 

structure,  498 
Salkowski's  reaction,  436 
Salmine,  427 
Salts  in  the  blood,  454 
Sanderson's  cardiograph,  239 

on  electrical  change  in  muscles,  125 
Sanson's  images,  824,  825 
Santorini's  cartilages,  800,  802 
Saponification,  416,  520 
Sarcinse,  439 
Sarcolemma,  63,  64,  137 
Sarcomeres,  67,  68 
Sarcoplasm,  65,  67,  72 
Sarcostyles,  65  et  seq. 


SENSORY  IMPRESSIONS. 

Sarcous  elements,  67  et  seq. 

Sartorius,  record  of  injured,  130 

Scala  media,  792 

Scalatypani,  791,  797 

Scala  vestibuli,  791,797 

Scarpa,  ganglion  of,  677 

Schiifer,  heart  plethysmograph,  260 

observations  on  liver  cells,  530 

method  of  artificial  respiration,  383,  384 

protoplasmic  structure,  7,  14 

researches  on  the  structure  of  a  sarcostyle,  67 

views  regarding  the  function  of  the  Rolandic 
area,  731 

white  blood  corpuscles,  8 
Scheiner's  experiment,  826 
Schematic  eye,  821 
Schenk  on  muscular  contraction,  115 
Schlemm,  canal  of,  813,  814 
Schmidt's  method  of  preparing  fibrin  ferment, 

453 

Schroder's  experiment,  587 
Schwann,  white  substance  of,  74 
Sclero-proteins,  427-429 
Sclerotic,  807,  808,  809,  811-813 
Scotoma,  849 
Scratch  reflex,  717,  718 
Sebaceous  glands,  608 
Sebum,  608 

Secondary  contraction,  128 
Secretin,  521 
Secreting  glands,  81,  492  et  seq. 

classification  of,  496 

diagram  of,  497 
Secreting  membranes.    See  Mucous    and  Serous 

membranes. 
Secretion,  internal,  331 

of  kidney,  571 
pancreas,  520 
saliva,  500 

paralytic,  503 

reflex,  504,  520 

suprarenal,  340 

thyroid,  337 
Secretory  nerves,  144 

diagram  of,  503 

of  pancreas,  521 

of  salivary  glands,  502 
effect  of  section  of,  503 

of  sweat  glands,  610 
Segmentation  of  cells,  883 

in  chick,  885 

nucleus,  876 
ovum,  883 
Semen,  866,  867 

spermatozoa,  ib. 
Semicircular  canals  of  ear,  794 

diagrams  of,  754,  755 

structure,  753  et  seq. 
Semilunar  valves.    See  Heart  valves. 
Semipermeable  membranes,  324 
Sensation,  760,  764 

cutaneous,  766  et  seq. 

difference  in  quality,  762 

extensity,  ib. 

hallucination,  764 

memory  image,  ib. 

nerves  of,  144 

tactile,  751 

thresholds,  763 

Weber's  law,  ib. 
Sensibility,  recurrent,  156 
Sensory  areas  in  cerebral  cortex,  728 
Sensory  channels,  diagram  of,  702 
Sensory   impressions,  conduction    of,   by  spinal 
cord,  144 

in  brain,  734  et  seq. 


INDEX 


919 


SENSORY  NERVE-ENDINGS  IN  MUSCLE. 

Sensory  nerve-endings  in  muscle,  769  ;  in  skin,  7f>6 

Sensory  nerves,  70 

Septum  nasi,  nerves  of,  785 

Serine,  417 

Serous  coat,  493 

Serous  membranes,  208 

Sertoli,  cells  of,  864 

Serum, 

albumin,  315,  453 

of  blood,  60,  452  et  seq. 

globulin,  315,  453 
Seventh  cerebral  nerve,  663,  673 
Sex,  determination  of,  859 
Sexual  organs  in  the  female,  867  ct  .T«/. 

in  the  male,  863  et  se<j. 
Sharpey  on  bone  formation,  50 

fibres  of,  44 
Sherrington, 

experiments  on  motor  area,  731 

on  course  of  reflex  in  knee  jerk,  712 

observations  on  binocular  flicker,  854 

principal  of  the  common  path,  716,  717 

reciprocal  action  of  antagonistic  muscles,  714, 

715 

Short  sight,  828 
Side-chain  theory,  475 
Sight.    See  Vision. 
Silent  areas,  738 
Silver  nitrate  reaction  of  cementing  substance, 

27 

Simple  tubular  glands,  496 
Sino-auricular  node,  213,  256 
Sinus,  coronary,  209 
Sinuses  of  Valsalva,  214,  237 
Sinusoids,  222,  528 
Sixth  cerebral  nerve,  663,  671 
Skein,  15, 16,  18 
Skeletal  muscles,  63 
Skiascopa,  831 
Skin, 604 

absorption  by,  608 

dermis,  604 

diseases,  611 

epidermis  of,  604 

functions  of,  608 

nerve-endings  in,  766 

papillae  of,  604 

respiration,  60S 

rete  mucosum  of,  604 

sebaceous  glands  of,  60S 

secretions,  ib. 

sections  of,  605  et  seq. 

sweat,  609  et  seq. 

sweat-glands,  496,  608 

varnishing  the,  611 
Sleep,  744  et  seq. 
Smell,  sense  of,  738,  782  ct  seq. 

anatomy  of  regions,  784 

connection  with  taste,  738 

delicacy  of  sense  of,  787 

tests  for,  varies  in  different  animals,  786 
Smith,  Lorrain,  experiments  on  quantity  of  the 

blood,  445 

Smith's  perimeter,  Priestly,  840 
Sneezing,  mechanism  of,  882 
Snoring,  mechanism  of,  ib. 
Soap,  416 
Sobbing,  382 

Sodium  chloride  method,  431 
Solitary  glands.    See  Peyer's  patches. 
Solubilities,  423 

Solutions,  gramme-molecular,  323 
Somatic  mesoblast,  872,  884,  887 
Somatoplasm,  ^  eismann's,  861 
Somatopleur,  884 
Somites,  mesoblastic,  884 


SPIRILLA,  VARIOUS  FORMS  OF. 

Sonorous  vibrations,  how  communicated  in  ear, 
794  et  seq. 

in  air  and  in  water,  795.    See  Sound. 
Sound, 

conduction  by  ear,  794 

heart,  235,  245 

production  of,  806 
Soup,  value  as  food,  490 

Sour  milk  as  cure  for  dyspeptic  disorders,  527 
Spaces  of  Pontana,  814 
Speaking,  mechanism  of,  807 
Special  senses,  766  et  seq. 
Specific  nerve  energy,  law  of,  762 
Spectroscope,  465  et  seq. 
Speech,  807  et  seq. 

centre,  733 

defects  of,  808 
Spermatidg,  864,  865,  873 
Spermatocytes,  ib. 
Spermatogonia,  ib. 
Spermatozoa,  19,  866,  867,  881 

form  and  structure  of,  866,  867 
Spheno-palatine  ganglion,  678 
Spherical  aberration,  830 

correction  of,  ib. 
Sphincter  ani.    See  Defalcation. 

pupillae,  812 

vesicae,  570 

Sphingomyelin,  166,  435,  438 
Sphygmographs,  291,  292 

tracings,  291  et  seq. 
Sphygmometers,  295 
Spinal  accessory  nerve,  664 

functions  of,  679 

origin,  ib. 
Spinal  cord,  648  et  seq. 

association  fibres  in,  658 

canal  of,  648 

columns  of,  649 

commissures  of,  648 

conduction  of  impressions  by,  704  et  seq. 

course  of  fibres  in,  653 

diagrams  of,  649,  650,  660 

fissures  and  furrow  <  of,  648 

functions  of,  704  et  seq. 
of  columns,  654 

grey  matter,  181,  650 
cells  in,  650 

hemisection,  659 

injuries  of,  704,  709 

membranes  of,  643 

nerves  of,  653 

reflex  action  of,  709  et  seq. 
inhibition  of,  710 
in  frog,  709 
in  man,  711 
superficial,  ib. 

reflex  irritability  of,  712 

regions  of,  659 

section  of,  ib. 

special  centres  in,  720 

structure  of,  648  et  seq. 

tracts,  651,  655,  703 

transverse  section  of,  659 

white  matter,  167,  649 

tracts  in,  651 
Spinal  nerves,  155 

functions  of  roots  of,  155,  649 

origin  of,  155  ct  seq. 
Spinal  visceral  reflexes,  721 
Spiral  canal  of  the  ear,  791 
Spiral  ganglion,  794 
Spiral  layer,  213 
Spiral  ligament  of  oar,  792 
Spirem,  15,  18 
Spirilla,  various  form?  of,  439 


920 


INDEX 


SPIROMETER. 

Spirometer,  359 
Splanchnic  mesoblast,  884,  887 
Splanchnic  nerves,  342 
Splanchnopleur,  884 
Spleen,  332 

apparatus  for  splenic  curves,  134,  313 
functions,  334 

influence  of  nervous  system  upon,  335 
Malpighian  corpuscles  of,  334 
pulp,  333 
structure  of,  332 
trabeculae  of,  ib. 
Spongioblasts,  816 
Spongioplasm,  7,  8, 14,  68,  83 
Spot,  germinal,  871 
Spring  myograph,  94 
Staircase  phenomenon,  97,  141,  259 
Stannius'  experiment,  258 
Stapedlus  muscle,  790,  796 
Stapes  or  stirrup  bone,  789,  790 
Staphylococci,  439 
Starch,  412,  537 
Starling  mammalian  heart,  245 

on  pancreatic  secretion,  520-525 
Starvation,  621,  628 

effects  of,  ib. 
Stearic  acid,  414 
Stearin,  34,  414 
Stellate  cells  of  Kupffer,  528 
Stercobilin,  534 
Stethographs,  357 
Stewart's 
experiments  on  the  circulation  of  the  blood, 

289,  290 

on  muscle  proteins,  142 
on  the  output  of  the  heart,  247 
Stimulants  as  accessories  to  food,  490 
Stimulation  fatigue,  134 
Stimuli,  varieties  of,  13, 14,  81,  84,  85 
Stirrup  bone,  789,  790 
Stokes'  reagent,  465 

Stolnikow,  measurement  of  the  heart's  output,  247 
Stomach, 
blood-vessels,  509 
digestion  in,  525,  563 
glands,  508 
movements,  553 

influence  of  nervous  system  on,  556 
mucous  membrane,  507 
nervous  mechanism  of,  556,  557,  563 
secretion  of.    See  Gastric  juice, 
time  taken  to  empty,  554 
view  of  empty,  555 
Stomata,  226 
Stratum  granulosum,  604 
intermedium  of  Hannover,  58 
lucidum,  604 
Streptococci,  439 
StrijB  acousticse,  663,  677 
Striated  muscle,  66  et  seq.    See  Muscle. 
Striatearea,  736 
Stroma,  454,  868 
Stromuhr,  Ludwig's,  282 

Tigerstedt's,  284 
Structure  of  cells,  8  et  seq. 
Stuart's  kymoscope,  271 
Sturine,  427 
Stylo-pharyngeus,  678 
Subendothelial  layer,  218 
Sublingual  gland,  503 
Submaxillary  gland  of  dog,  499 
Submaxillary  and  sublingual  glands,  499,  500 
Submaxillary  ganglion,  502 
Submucous  coat,  493 

Substantia  gelatiuosa  of  Rolando,  650,  667,  668 
nigra,  672,  673 


TEMPERATURE. 

Substrate,  439 
Subthalamic  area,  689 
Succagogues,  513 
Succus  entericus,  522  et  seq. 

functions  of,  ib. 
Sucroses,  409 

Sugar.    See  Dextrose,  Lactose,  etc. 
Sulci,  690  et  seq.,  730,  731 
Sulphates  in  urine,  595 
Summation-tones,  797 
Superficial  reflexes,  711 

Superior  laryngeal  nerve,  effects  of  stimulation 
of  cut,  378 

olivary  nucleus,  671 

parietal  convolution,  693 
Supra-renal  capsules,  340 

cortex,  342 

function,  341 

structure,  340 
Surface  tension,  330 
Sustentacular  fibres  of  Miiller,  815,  816 
Swallowing,  551 

centre,  ib. 

fluids,  552 

nerves  engaged,  ib. 
Sweat,  609  et  seq. 
Sweat-glands.    See  Skin. 
Sylvius,  aqueduct  of,  644,  645,  663,  671 
Sylvius,  fissure  of,  642,  643,  692-694 
Sympathetic  nerve,  251 
Sympathetic  secretion,  502 
Syntonin,  434 
Syringomyelia,  707 

Systemic  circulation,  215.    See  Circulation. 
Systole  of  heart,  232 
Systolic  pressure,  296 
Systolic  sound,  235 


T. 

Tabes  dorsalis,  715 
Tache  cerebrale,  311 
Tactile  area,  734 

discs,  770 

end-organs,  766  et  seq. 

impressions,  751 

sensibility,  734,  770,  771 

variations  in,  772 
Talbot's  law,  836 
Tapetum  lucidum,  837  n. 
Tarsus,  810 
Taste,  sense  of,  738,  779  et  seq. 

classification  of,  783 

connection  with  smell,  738 

delicacy  of,  783 

nerves  of,  781 
Taste-buds,  781,  782 
Taurine,  533 
Taurocholic  acid,  ib. 
Taxis,  positive  and  negative,  14  n. 
Tchistovitch's  discovery  of  distinguishing  human 

and  other  blood,  477 
Teeth,  50  et  seq. 

development,  56 

eruption,  times  of,  51 

incisor,  51 

structure,  52  et  seq. 

temporary  and  permanent,  50  e.t  seq. 
Tegmental  nucleus,  671 
Tegmentum,  ib. 
Telencephalon,  645 
Temperature,  368,  636  et  seq. 

average  of  body,  636 

changes  of,  effects,  686  et  seq. 


INDEX 


921 


TEMPERATURE. 

Temperature— continued 

effect  on  muscular  contraction,  99 

extensibility,  influence  on,  112 

of  cold-blooded  and  warm-blood«d  animals,  636 

in  disease,  641 

loss  of,  638-641 

maintenance  of,  636 

of  Mammalia,  birds,  etc.,  ib. 

sensation  of  variation  of,  772.    See  Heat. 
Temporo-occipital  cerebellar  fibres,  673 
Temporo-sphenoidal  lobe,  692,  693 
Tendon-reflexes,  711,  712 
Tension  of  gases  in  fluids,  365 
Tensor  palati  muscle,  795 

tympani  muscle,  790,  796 

action  of,  795 
Terminal  areas,  743 
Terminal  ganglia,  249 
Testicle,  863,  864 

structure,  ib. 
Testis,863,  878 

internal  secretions  of,  878 
Tetanus,  composition  of,  103 

injured  sartorius  during,  126 

Hitter's,  176 

voluntary,  104, 142 
Tetany, 340 

Thalamencephalon,  645 
Thalami  optici,  688 
Theine,  490 
Theobromine,  ib. 
Thermopile,  130 
Thirst,  778 

Thoma-Zeiss  hremacytometer,  458 
Thomson's  galvanometer,  118 
Thoracic  duct,  61,  224 

innervation  of,  319 
Thresholds  of  the  stimulus,  763 
Throat  deafness,  795 

ventricle,  801 

Thrombin,  440,  448,  449,  453 
Thrombogen,  449-451 
Thrombokinase,  ib. 
Thudichum  on  protagon,  437 
Thymus  gland,  336 

effects  of  removal,  337 

function,  ib. 

structure,  336 

Thyro-arytenoid  muscle,  801,  802 
Thyro-epiglottidean  muscle,  802 
Thyroid  cartilage,  799 
Thyroid  gland,  337 

function,  342 

structure,  337 
Thyro-iodin,  339 

effect  of  Intravenous   injection  of,  on    blood- 
pressure,  339 

Tigerstedt,  measurement  of  the  heart's  output, 
247,  290 

Stromuhr,  284 
Timbre  of  voice,  794,  806 
Tissue-erepsin,  546,  593 
Tissue-respiration,  394  et  seq. 
Tongue,  779 

action  in  deglutition,  548 

epithelium  of,  780 

muscles  of,  779 

papilla;  of,  ib. 

parts  most  sensitive  to  taste,  781 

structure  of,  779 
Tonometer,  Barcroft's,  366 

Krogh's,  366,  373 
Tonus,  113,  142,  713 
Topfer's  test,  516 
Touch,  766  et  seq. 

muscular  sense,  776 


URETERS. 

Touch— continued 

sense  of  locality,  770 
of  pressure,  771 
of  temperature,  Hi. 

tactile  end -organs,  766 
Touch-corpuscles,  767 
Toxin,  474 
Trabeculse,  317,  332 
Trachea,  347 
Tract  of  Flechsig,  658 

of  Gpwers,  657,  658 

of  Lissauer,  ib. 

of  Loewenthal,  656 

Tracts  in  the  spinal  cord,  651,  655  ct  seq. 
Tradescantia,  cells  of,  12,  13 
Transfusion  of  blood,  319 
Transmission  myograph,  105,  159 
Transverse  axis  of  eyeball,  851 
Trapezium,  the,  671 
Traube-Hering  curves,  304,  305 
Triacetin,  415 

Triamino-mono  phosphatides,  485 
Tricuspid  valve,  210,  213 
Trigeminal  nerve,  663,  674 

function,  674 

origin  of,  ib. 
Trimethylamine,  166 
Trochlear  nerve,  663,  674 

origin  of,  674 
Trommer's  test,  412 
Trophic  nerves,  144 
Trypsin,  action  of,  518,  519 
Trypsinogen,  523,  524 
Tryptophane,  419,  422 
Tubercle  of  Rolando,  667 
Tubular  glands,  496,  497 
Tubuli  seminiferi,  864,  865 

uriniferi,  566  et  seq. ,  569 
Tubulo  -  racemose    or    tubulo  -  acinous    glands, 

496 

Tunica  adventitia,  217 
Tunica  albuginea  of  testicle,  863 

dartos,  72 

propria,  753 

vaginalis,  863 
Tiirck's  column,  655 

method  of  cumulation  of  reflexes,  710 
Tympanum  or  middle  ear,  788 

diagram  of,  780 

membrane  of,  788,  790 

muscles  of,  790 

structure,  788 
Tyrosine,  418,  419,  422 


u. 

Umbilical  arteries,  890 

cord,  888,  890 

vesicle,  887 

Uncinate  convolution,  694 
Unicellular  organisms,  5 
Unilaminar  blastoderm,  883 
Unimolecular  reactions,  329 
Uremia,  588,  611 
Urate  of  sodium,  598 
Urates,  deposit  of,  598,  600 
Urea,  166,  583 

apparatus  for  estimating  quantity,  585 

chemical  composition  of,  583 

formation  of,  by  liver,  528,  586 

isomeric  with  ammonium  cyanate,  583 

quantity,  586 
Ureters,  565,  570 


922 


INDEX 


UBKTHRA. 

Urethra,  565,  570 
Uric  acid,  166,  432,  591 

condition  in  which  it  exists  in  urine,  593 

crystals,  various  forms  of,  591 

deposit  of,  598 

forms  in  which  it  is  deposited,  591 

origin  of,  583,  593 

presence  in  the  spleen,  335 

presence  in  the  urine,  600 

proportionate  quantity  of,  592 

tests,  592 

Uricolytic  enzyme,  594 
Urina  potus,  583 
Urinary  apparatus,  565  et  seq. 
Urinary  bladder,  570 

nerves,  ib. 

structure,  ib. 

Urinary  deposits,  598  et  seq. 
Urine,  582  et  seq. 

analysis  of,  583 

bile  in,  602 

blood  in,  603 

chemical  sediments  in,  600 

colour,  582 

composition,  583 

cystine  in,  599 

expulsion,  580 

flow  into  bladder,  579 

hippuric  acid  in,  594 

inorganic  constituents,  595 

mineral  salts  in,  ib. 

pathological,  600 

phosphates  in,  597,  599 

physical  characters,  582 

pigments,  ib. 

proteins,  600 

pus  in,  601,  603 

quantity,  582 
varies  with  blood-pressure,  572 

reaction  of,  582 
in  different  animals,  583 
made  alkaline  by  diet,  ib. 

saline  matter,  583,  588 

solids,  582 

specific  gravity  of,  583 
variations  of,  ib. 

sugar  in, 601,  602 
tests  for  estimating,  602 

tests  for  inorganic  salts  of,  597 

urates,  598 

urea,  583 

uric  acid  in,  591 

Uriniferous  tubes,  diagram  of,  566 
Urobilin,  534,  582 
Urochrome,  582 
Uro-erythrin,  582,  594 
Uterine  muscle,  890 

reflexes,  721 
Uterus,  867,  871 

atrophy  or  involution  of,  895 

development  in  pregnancy,  893 

diagram  of,  867,  887-890 

structure,  871 
Utricle,  791 
Uvea,  812 


V. 

Vaccination,  473 
Vagina,  867 

Vago-sympathetic  of  frog,  251 
Vagus, 

electrical  variations  in,  377,  378 

escape,  251 

nerve.    See  Pneumogastric. 


VISCERAL  LAYER  OF  PERICARDIUM. 

Valentine's    experiments    on    velocity    of   blood 

flow,  281 
Valine,  417 

Valsalva's  experiment,  388 
Valves  of  heart,  213.    See  Heart. 
Vas  deferens,  864,  865,  879 
Vasa  efferentia  of  testicle,  864,  865 
Vasa  vasorum,  218 
Vascular  system,  in  asphyxia,  389 
Vaso-constrictor  nerves,  300,  302 
Vaso-dilator  nerves,  300,  303 
Vaso-motor  nerves,  264,  300 

distribution  of,  302 

effect  of  section,  307  et  seq. 

experiments  on,  306,  307 

influence  upon  blood-pressure,  306 

stimulation  fatigue,  135 
Vaso-motor  nerve-centres,  301,  303,  305,  721 

nervous  system,  800  et  seq. 

reflex  action,  305 
Vegetables  as  food,  479, 490 
Vegetable  cells,  5 

protoplasmic  movement  in,  12, 13 
Veins,  208,  214,  218  et  seq. 

circulation  in,  299  et  seq. 
velocity  of,  281 

distribution,  218 

interlobular,  569 

pressure  in,  278 

pulmonary,  219 

rhythmical  action  in,  299 

structure  of,  219 

valves  of,  219  et  seq. 
Velocity  head,  286 

pulse,  284,  300 

Velocity  of  blood  in  arteries,  281 
in  capillaries,  ib. 
in  veins,  ib. 

of  circulation,  ib. 

of  enzyme  action,  516,  520 

of  nervous  impulse,  159 
Vena  cava,  210 
Venae  rectae,  570 
Venae  stellulse,  569 
Venous  flow,  299 
Ventilation,  379,  384 
Ventral  cerebellar  tract,  658 
Ventricles  of  the  brain,  644 
Ventricles  of  heart.    See  Heart. 
Ventricular  diastole,  233,  23 1 

systole,  ib. 

Veratrine,  effect  of,  on  muscular  contraction,  99 
Vernon,  heat  rigor  experiment,  139 

on  tissue-erepsin,  546 

pancreatic  secretion,  523 
Vertical  axis  of  eyeball,  851 
Verworn,  Max,  strychnine  and  fatigue,  135 
Vesical  centre,  580 
Vesicle, 

germinal,  18 
Vesiculae  seminales,  865 
Vestibular  nerve,  663 
Vestibule  of  osseous  internal  ear,  753,  790 
Vibrations,  conveyance  of,  to  auditory  nerve,  796 

et  seq. 
Vierordt's     experiments     on     blood-circulation, 

289 

Vierordt's  haematachometer,  287 
Vieussen's  annulus,  196,  251,  302 
Villi  in  chorion,  function  of,  888 

of  intestines,  494,  495 
Vincent,  Swale,  muscle  proteins,  142 
Visceral  layer  of  pericardium,  208 

mesoblast,  884 

pain,  777 

sensations,  777 


INDEX 


923 


VISION. 

Vision,  810 

angle  of,  822 

at  different  distances,  adaptation  of  eye  to,  824 
et  seq. 

correction  of  aberration,  830  et  seq. 

defects  of,  828  et  seq. 

distinctness,  how  secured,  856  et  seq. 

duration  of  sensation  in,  836 

estimation  of  the  size  and  form  of  objects,  854- 
856 

focal  distance  of,  824 

range,  827 

relation  of  nerve-cells  arid  fibres,  854 

single,  with  two  eyes,  850  et  seq. 
Visual  area,  735 

apparatus,  relations  of  nerve-cells  and  fibres, 
854 

axis,  822,  851 

impressions,  752 

judgments,  854  et  seq. 

plane,  851 

purple,  817,  847 

sensations,  836,  841  et  seq. 

word-centre,  741,  809 
Visuo-psychic  region,  737 
Visuo-sensory  cortex,  ib. 
Vital  action,  327 

force,  2 
Vitamine,  491 
Vitellin,  429,  487 

membrane,  871 
Vitello-intestinal  duct,  886 
Vitreous  humour,  811,  819 
Vocal  cords,  801 

action  in  respiratory  actions,  804 

approximation  of,  etfect  on  height  of  note,  805 

vibrations  of,  cause  voice,  806 
Voice,  799  et  seq.,  806 

range  of,  806 
Volt's  diet,  480,  618,  629 

on  "  circulating  protein,"  622 
Volkmann's  haemadromometer,  282 

experiment  on  lymph  hearts,  318,  319 
Volta  on  galvanism,  116 
Voluntary  muscle,  63  et  seq.,  140  et  seq. 

nerves  of,  70 
Voluntary  tetanus,  104 
Vomiting,  556,  557 

action  of  stomach  in,  ib. 

centre,  ib. 

nerve  actions  in,  ib. 

voluntary  and  acquired,  ib. 
Vorticellae,  82 

Vowels  and  consonants,  808 
Vulpian's    experiments   on    nerve   regeneration, 
149, 151 


w. 

Wagner's  hammer,  90 

Wallerian  degeneration  method,  146,  149,  151, 156, 

651,  652 
Waller,  dynamograph,  132 

electrocardiogram,  245 

fatigue  theory,  133 

on  the  electrical  currents  of  the  eyeball,  849 

on  the  passage  of  blood-corpuscles,  297, 298 


ZYMOLYSIS. 

Waller— continued 

on  work  of  heart,  247 

"  sound-picture  "  theories  of,  798 

variation  in  nerve  action,  159 
Wander  cells,  31 
Water-hammer  pulse,  291 
Wave  of  blood  causing  the  pulse,  ib. 

velocity  of,  ib. 
Weber-Fechner  law,  763 
Weber's  experiment  on  velocity  of  blood-flow,  281 

on  heart- beats,  249 
Weber's  paradox,  112, 114 
Weigert's  method,  651,  739 
Weismann's  germ  plasm,  859,  861 

somatoplasm,  861 

Wertheimer's  investigations  into  pancreatic  secre- 
tion, 520 

Wharton's  jelly,  36 
Whey  protein,  482 

White  corpuscles.    See  Blood-corpuscles,  white  ; 
and  Lymph-corpuscles. 

emigration  of,  298 
White  fibro-cartilage,  37,  38 

fibrous  tissue,  29,  80 

spot,  814 

Widal's  reaction,  476 
Wooldridge's  method  of  preparing  tissue-fibrino- 

gen,  431 

Word- centres,  809 
Worms,  circulatory  system  in,  230 
Wright,  Hamilton,  sleep  theory,  746 
Wright's  opsonins,  476 
Wrisberg,  cartilages  of,  800,  805 

pars  intermedia  of,  675 


Xanthine,166,  432 
Xantho-proteic  reaction,  425 


Y. 


Yawning,  mechanism  of,  382 

Yeast  plant,  cells  of,  in  process  of  budding,  5,  439 

Yellow  elastic  fibre,  29,  30 

fibro-cartilage,  37,40 

marrow,  41 

spot  of  Sommering,  814 
Yeo's  experiment  on  gaseous  exchanges  in  the 

heart,  254 

Yolk-sacs,  888  et  seq. 
Yolk-spherules,  870 
Young-Helmholtz  theory,  842  et  seq. 


Zona  fasciculata,  340 

Zona  pellucida,  or  striata,  19,  870,  881 

Zonule  of  Zinn,  820 

Zuntz,  on  mountain  sickness,  400 

Zymase,  439 

Zymogen,  441,  449,  499,  509 

Zymolysis,  reversible,  614 


PRINTED   BY 

OLIVER   AND   BOYD 

EDIN BURGH 


DATE    DUE    SLIP 

UNIVERSITY  OF  CALIFORNIA  MEDICAL  SCHOOL  LIBRARY 

THIS  BOOK  IS  DUE  ON  THE  LAST  DATE 
STAMPED  BELOW 


AUG  26  1924 


MOV  12  1931 

OCT.  12  1945 
OCT  2  5 


2m-12,'19 


Library  of  the 
University  of  California  Medical  School  and  Hospitals 


